The effect of three different crop rotations on a saline Solonetzic soil over a period of five years

Non-Peer Reviewe

EORTC-related new drug discovery and development activities: role of the Pharmacology and Molecular Mechanisms Group

Abstract The EORTC Pharmacology and Molecular Mechanism Group (PAMM) focuses on applied research to translate basic/fundamental research discoveries in cancer biology into new drug discovery and development. PAMM provides a unique platform on the pharmacology, pharmacokinetics, pharmacodynamics of drug effects, molecular mechanisms of anticancer agents, and drug-related molecular pathology. For these purposes the group stimulates the interaction between basic scientists and clinicians in order to perform translational research on the pharmacology and molecular mechanisms of anticancer agents in Europe. The group has extensive expertise in various disciplines of pharmacology and has developed standards for studies performed in conjunction with clinical trials equivalent to those of good laboratory practice (GLP). The group serves as master organization for other EORTC (sub-)committees in the maximal interest of these groups and of the EORTC as a whole. PAMM merged with Preclinical Therapeutics Models Group (PTMG) in 2000 and with the Screening and Pharmacology Group (SPG) in 2003. The latter group continued as the Drug Discovery Committee within PAMM. The groups have always been involved in the development of anticancer agents, evolving from platinum analogs, anthracyclines, nitrosoureas, antifolates in the 1980's, to drugs derived from natural sources (trabectedin, taxanes) in the 1990's, and anti-signaling drugs, DNA alkylators, in the last decade. Several of these drugs have been registered. Mechanistic studies focused on drug activation/inactivation, target (DNA, receptors) in relation to efficacy and toxicity such as with several antimetabolites (5-fluorouracil, methotrexate), topoisomerase inhibitors (irinotecan), tyrosine kinase inhibitors (imatinib), acridones (C-1311), etc. The group recently included pharmacogenetics in the identification of genetic polymorphisms in order to use this information for personalized therapy

Does unconscious perception really exist? Continuing the ASSC20 debate

In our ASSC20 symposium, “Does unconscious perception really exist?”, the four of us asked some difficult questions about the purported phenomenon of unconscious perception, disagreeing on a number of points. This disagreement reflected the objective of the symposium: not only to come together to discuss a single topic of keen interest to the ASSC community, but to do so in a way that would fairly and comprehensively represent the heterogeneity of ideas, opinions, and evidence that exists concerning this contentious topic. The crux of this controversy rests in no small part on disagreement about what is meant by the terms of the debate and how to determine empirically whether a state is unconscious or not. These are issues that directly concern all of us who study consciousness, so it seems it would be in our best interest to strive for consensus. Given the conversation at ASSC20, we are pleased to have the opportunity to address some of the nuanced topics that arose more formally, and share some of the thinking we have done since the meeting. To reflect the heterogeneity of ideas and opinions surrounding this topic, we have organized this discussion into four distinct contributions

Rewiring strategies for changing environments

A typical pervasive application executes in a changing environment: people, computing resources, software services and network connections come and go continuously. A robust pervasive application needs adapt to this changing context as long as there is an appropriate rewiring strategy that guarantees correct behavior. We combine the MERODE modeling methodology with the ReWiRe framework for creating interactive pervasive applications that can cope with changing environments. The core of our approach is a consistent environment model, which is essential to create (re)configurable context-aware pervasive applications. We aggregate different ontologies that provide the required semantics to describe almost any target environment. We present a case study that shows a interactive pervasive application for media access that incorporates parental control on media content and can migrate between devices. The application builds upon models of the run-time environment represented as system states for dedicated rewiring strategies

Rho-omega mixing in asymmetric nuclear matter via QCD sum rule approach

We evaluate the operator product expansion (OPE) for a mixed correlator of the isovector and isoscalar vector currents in the background of the nucleon density with intrinsic isospin asymmetry [i.e. excess of neutrons over protons] and match it with its imaginary part, given by resonances and continuum, via the dispersion relation. The leading density-dependent contribution to $\rho-\omega$ mixing is due the scattering term, which turns out to be larger than any density dependent piece in the OPE. We estimate that the asymmetric density of $n_n-n_p \sim 2.5 \times 10^{-2} ~{\rm fm^3}$ induces the amplitude of $\rho-\omega$ mixing, equal in magnitude to the mixing amplitude in vacuum, with the constructive interference for positive and destructive for negative values of $n_n-n_p$. We revisit sum rules for vector meson masses at finite nucleon density to point out the numerical importance of the screening term in the isoscalar channel, which turns out to be one order of magnitude larger than any density-dependent condensates over the Borel window. This changes the conclusions about the density dependence of $m_\omega$, indicating $\sim 40$ MeV increase at nuclear saturation density.Comment: 8 pages, Revte

Aspects of meson properties in dense nuclear matter

We investigate the modification of meson spectral densities in dense nuclear matter at zero temperature. These effects are studied in a fully relativistic mean field model which goes beyond the linear density approximation and also includes baryon resonances. In particular, the role of N*(1520) and N*(1720) on the rho meson spectral density is highlighted. Even though the nucleon-nucleon loop and the nucleon-resonance loop contribute with the opposite sign, an overall reduction of rho meson mass is still observed at high density. Importantly, it is shown that the resonances cause substantial broadening of the rho meson spectral density in matter and also induces non-trivial momentum dependence. The spectral density of the a0 meson is also shown. We study the dispersion relations and collective oscillations induced by the rho meson propagation in nuclear matter together with the influence of the mixing of rho with the a0 meson. The relevant expression for the plasma frequency is also recovered analytically in the appropriate limit.Comment: 19 pages, 17 figure

The global carbon budget 1959-2011

Accurate assessments of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the climate policy process, and project future climate change. Present-day analysis requires the combination of a range of data, algorithms, statistics and model estimates and their interpretation by a broad scientific community. Here we describe datasets and a methodology developed by the global carbon cycle science community to quantify all major components of the global carbon budget, including their uncertainties. We discuss changes compared to previous estimates, consistency within and among components, and methodology and data limitations. CO2 emissions from fossil fuel combustion and cement production (EFF) are based on energy statistics, while emissions from Land-Use Change (ELUC), including deforestation, are based on combined evidence from land cover change data, fire activity in regions undergoing deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. Finally, the global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms. For the last decade available (2002–2011), EFF was 8.3 ± 0.4 PgC yr−1, ELUC 1.0 ± 0.5 PgC yr−1, GATM 4.3 ± 0.1PgC yr−1, SOCEAN 2.5 ± 0.5 PgC yr−1, and SLAND 2.6 ± 0.8 PgC yr−1. For year 2011 alone, EFF was 9.5 ± 0.5 PgC yr−1, 3.0 percent above 2010, reflecting a continued trend in these emissions; ELUC was 0.9 ± 0.5 PgC yr−1, approximately constant throughout the decade; GATM was 3.6 ± 0.2 PgC yr−1, SOCEAN was 2.7 ± 0.5 PgC yr−1, and SLAND was 4.1 ± 0.9 PgC yr−1. GATM was low in 2011 compared to the 2002–2011 average because of a high uptake by the land probably in response to natural climate variability associated to La Niña conditions in the Pacific Ocean. The global atmospheric CO2 concentration reached 391.31 ± 0.13 ppm at the end of year 2011. We estimate that EFF will have increased by 2.6% (1.9–3.5%) in 2012 based on projections of gross world product and recent changes in the carbon intensity of the economy. All uncertainties are reported as ±1 sigma (68% confidence assuming Gaussian error distributions that the real value lies within the given interval), reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. This paper is intended to provide a baseline to keep track of annual carbon budgets in the future

A cross-sectional survey of 5-year-old children with non-syndromic unilateral cleft lip and palate:the Cleft Care UK study. Part 1: background and methodology

OBJECTIVES: We describe the methodology for a major study investigating the impact of reconfigured cleft care in the United Kingdom (UK) 15 years after an initial survey, detailed in the Clinical Standards Advisory Group (CSAG) report in 1998, had informed government recommendations on centralization. SETTING AND SAMPLE POPULATION: This is a UK multicentre cross-sectional study of 5-year-olds born with non-syndromic unilateral cleft lip and palate. Children born between 1 April 2005 and 31 March 2007 were seen in cleft centre audit clinics. MATERIALS AND METHODS: Consent was obtained for the collection of routine clinical measures (speech recordings, hearing, photographs, models, oral health, psychosocial factors) and anthropometric measures (height, weight, head circumference). The methodology for each clinical measure followed those of the earlier survey as closely as possible. RESULTS: We identified 359 eligible children and recruited 268 (74.7%) to the study. Eleven separate records for each child were collected at the audit clinics. In total, 2666 (90.4%) were collected from a potential 2948 records. The response rates for the self-reported questionnaires, completed at home, were 52.6% for the Health and Lifestyle Questionnaire and 52.2% for the Satisfaction with Service Questionnaire. CONCLUSIONS: Response rates and measures were similar to those achieved in the previous survey. There are practical, administrative and methodological challenges in repeating cross-sectional surveys 15 years apart and producing comparable data

A Model for the Development of the Rhizobial and Arbuscular Mycorrhizal Symbioses in Legumes and Its Use to Understand the Roles of Ethylene in the Establishment of these two Symbioses

We propose a model depicting the development of nodulation and arbuscular mycorrhizae. Both processes are dissected into many steps, using Pisum sativum L. nodulation mutants as a guideline. For nodulation, we distinguish two main developmental programs, one epidermal and one cortical. Whereas Nod factors alone affect the cortical program, bacteria are required to trigger the epidermal events. We propose that the two programs of the rhizobial symbiosis evolved separately and that, over time, they came to function together. The distinction between these two programs does not exist for arbuscular mycorrhizae development despite events occurring in both root tissues. Mutations that affect both symbioses are restricted to the epidermal program. We propose here sites of action and potential roles for ethylene during the formation of the two symbioses with a specific hypothesis for nodule organogenesis. Assuming the epidermis does not make ethylene, the microsymbionts probably first encounter a regulatory level of ethylene at the epidermis–outermost cortical cell layer interface. Depending on the hormone concentrations there, infection will either progress or be blocked. In the former case, ethylene affects the cortex cytoskeleton, allowing reorganization that facilitates infection; in the latter case, ethylene acts on several enzymes that interfere with infection thread growth, causing it to abort. Throughout this review, the difficulty of generalizing the roles of ethylene is emphasized and numerous examples are given to demonstrate the diversity that exists in plants

A TALEN Genome-Editing System for Generating Human Stem Cell-Based Disease Models

SummaryTranscription activator-like effector nucleases (TALENs) are a new class of engineered nucleases that are easier to design to cleave at desired sites in a genome than previous types of nucleases. We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types. We demonstrate cell-autonomous phenotypes directly linked to disease—dyslipidemia, insulin resistance, hypoglycemia, lipodystrophy, motor-neuron death, and hepatitis C infection. We found little evidence of TALEN off-target effects, but each clonal line nevertheless harbors a significant number of unique mutations. Given the speed and ease with which we were able to derive and characterize these cell lines, we anticipate TALEN-mediated genome editing of human cells becoming a mainstay for the investigation of human biology and disease