The relationship between biophysical variables and halocarbon distributions in the waters of the Amundsen and Ross Seas, Antarctica

Little is known regarding the distribution of volatile halogenated organic compounds (halocarbons) in Antarctic waters and their relation to biophysical variables. During the austral summer (December to January) in 2007-08 halocarbon and pigment concentrations were measured in the Amundsen (100-130 degrees W) and Ross Sea (158 degrees W-160 degrees E). In addition, halocarbons were determined in air, snow and sea ice. The distribution of halocarbons was influenced to a large extent by sea ice, and to a much lesser extent by pelagic biota. Concentrations of naturally produced halocarbons were elevated in the surface mixed layer in ice covered areas compared to open waters in polynyas and in the bottom waters of the Ross Sea. Higher concentrations of halocarbons were also found in sea ice brine compared to the surface waters. Incubations of snow revealed an additional source of halocarbons. The distribution of halocarbons also varied considerably between the Amundsen and Ross Seas, mainly due to the different oceanographic settings. For iodinated compounds, weak correlations were found with the presence of pigments indicative of Phaeocystis, mainly in the Ross Sea. Surface waters of the Amundsen and Ross Seas are a sink for bromoform (saturation anomalies, SA, -83 to 11%), whereas sea ice was found to be both a source and sink (SA -61-97%). In contrast, both surface waters and sea ice were found to be a source of chloroiodomethane (SA -6-1 200% and 91-22 000 resp.). Consequently, polar waters can have a substantial impact on global halocarbon budgets and need to be included in large-scale assessments. (C) 2012 Elsevier B.V. All rights reserved

Contribution of sea ice in the Southern Ocean to the cycling of volatile halogenated organic compounds

The contribution of sea ice to the flux of biogenic volatile halogenated organic compounds to the atmosphere in the Southern Ocean is currently not known. To approach this question, we measured halocarbons in sea ice, sea ice brine, and surface water of the Amundsen and Ross Seas. Concentrations in sea ice of these compounds, normalized to seawater salinity, ranged from 0.2 to 810 pmol L-1. Salinity-normalized chlorophyll a concentrations in the ice ranged from 3.5 to 190 mu gL(-1). Our results suggest biological production of halocarbons in sea ice, with maxima of halogenated organics and chlorophyll a commonly found in the interior of the ice cores. Iodinated VHOCs were found to be more enriched in sea ice than brominated ones. Furthermore, depth distributions indicated a transport of halocarbons from sea ice to air and underlying water

Nuclear accessibility of β-actin mRNA is measured by 3D single-molecule real-time tracking

Imaging single proteins or RNAs allows direct visualization of the inner workings of the cell. Typically, three-dimensional (3D) images are acquired by sequentially capturing a series of 2D sections. The time required to step through the sample often impedes imaging of large numbers of rapidly moving molecules. Here we applied multifocus microscopy (MFM) to instantaneously capture 3D single-molecule real-time images in live cells, visualizing cell nuclei at 10 volumes per second. We developed image analysis techniques to analyze messenger RNA (mRNA) diffusion in the entire volume of the nucleus. Combining MFM with precise registration between fluorescently labeled mRNA, nuclear pore complexes, and chromatin, we obtained globally optimal image alignment within 80-nm precision using transformation models. We show that {beta}-actin mRNAs freely access the entire nucleus and fewer than 60% of mRNAs are more than 0.5 {my}m away from a nuclear pore, and we do so for the first time accounting for spatial inhomogeneity of nuclear organization

Cooling process for inelastic Boltzmann equations for hard spheres, Part II: Self-similar solutions and tail behavior

We consider the spatially homogeneous Boltzmann equation for inelastic hard spheres, in the framework of so-called constant normal restitution coefficients. We prove the existence of self-similar solutions, and we give pointwise estimates on their tail. We also give general estimates on the tail and the regularity of generic solutions. In particular we prove Haff 's law on the rate of decay of temperature, as well as the algebraic decay of singularities. The proofs are based on the regularity study of a rescaled problem, with the help of the regularity properties of the gain part of the Boltzmann collision integral, well-known in the elastic case, and which are extended here in the context of granular gases.Comment: 41 page

Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel

Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients, and have substantially decreased the prevalence of such events since their introduction. Today, a broad range of BP with differences in potency, efficacy, dosing, and administration as well as approved indications is available. In addition, results of clinical trials investigating the efficacy of BP in cancer treatment-induced bone loss (CTIBL) have been recently published. The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations. An interdisciplinary expert panel of clinical oncologists and of specialists in metabolic bone diseases assessed the widespread evidence and information on the efficacy of BP in the metastatic and nonmetastatic setting, as well as ongoing research on the adjuvant use of BP. Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3-4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancer

Agile in the Era of Digitalization : A Finnish Survey Study

This paper was a Candidate for the Best Full Paper.Peer reviewe

Toward Enriched Conceptions of Work Learning: Participation, Expansion, and Translation Among Individuals With/In Activity

Despite the long recognition in HRD theory that learning is socially and materially situated in activity and relations, HRD literature indicates a continuing strong emphasis on individualistic theories representing learning as knowledge acquisition or individual development. It is argued here that understandings of work learning within HRD theory can be fruitfully enriched by more fully incorporating practice-based perspectives. Three contemporary theories that analyse learning as a relation of individuals with/in activity have been selected for discussion here: the participational perspective of situated cognition, the notion of expansion from cultural-historical activity theory, and the constructs of translation and mobilization presented by actor-network theory. While these are not particularly new to HRD, the contribution of this discussion is to bring together these theories, along with published empirical workplace research based on them, to highlight selected dynamics that may be useful tools for HRD theory development. One element in particular is read across the three theories: the dialectic of ‘flying’ and ‘grounding’, or lines of discontinuity and continuity characterising work learning. The argument is theory-driven, drawing from HRD literature of work learning and practice-based theories of social activity and knowledge production

AMPA Receptor Activation Causes Silencing of AMPA Receptor-Mediated Synaptic Transmission in the Developing Hippocampus

Agonist-induced internalization of transmembrane receptors is a widespread biological phenomenon that also may serve as a mechanism for synaptic plasticity. Here we show that the agonist AMPA causes a depression of AMPA receptor (AMPAR) signaling at glutamate synapses in the CA1 region of the hippocampus in slices from developing, but not from mature, rats. This developmentally restricted agonist-induced synaptic depression is expressed as a total loss of AMPAR signaling, without affecting NMDA receptor (NMDAR) signaling, in a large proportion of the developing synapses, thus creating AMPAR silent synapses. The AMPA-induced AMPAR silencing is induced independently of activation of mGluRs and NMDARs, and it mimics and occludes stimulus-induced depression, suggesting that this latter form of synaptic plasticity is expressed as agonist-induced removal of AMPARs. Induction of long-term potentiation (LTP) rendered the developing synapses resistant to the AMPA-induced depression, indicating that LTP contributes to the maturation-related increased stability of these synapses. Our study shows that agonist binding to AMPARs is a sufficient triggering stimulus for the creation of AMPAR silent synapses at developing glutamate synapses

Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I-BFM Study Group

To study the prognostic relevance of rare genetic aberrations in acute myeloid leukemia (AML), such as t(16;21), international collaboration is required. Two different types of t(16;21) translocations can be distinguished: t(16;21)(p11;q22), resulting in the FUS-ERG fusion gene; and t(16;21)(q24;q22), resulting in RUNX1-core binding factor (CBFA2T3). We collected data on clinical and biological characteristics of 54 pediatric AML cases with t(16;21) rearrangements from 14 international collaborative study groups participating in the international Berlin-Frankfurt-Münster (I-BFM) AML study group. The AML-BFM cohort diagnosed between 1997 and 2013 was used as a reference cohort. RUNX1-CBFA2T3 (n 5 23) had significantly lower median white blood cell count (12.5 3 109/L, P 5 .03) compared with the reference cohort. FUS-ERG rearranged AML (n 5 31) had no predominant French-American-British (FAB) type, whereas 76% of RUNX1-CBFA2T3 had an M1/M2 FAB type (M1, M2), significantly different from the reference cohort (P 5 .004). Four-year event-free survival (EFS) of patients with FUS-ERG was 7% (standard error [SE] 5 5%), significantly lower compared with the reference cohort (51%, SE 5 1%, P < .001). Four-year EFS of RUNX1-CBFA2T3 was 77% (SE 5 8%, P 5 .06), significantly higher compared with the reference cohort. Cumulative incidence of relapse was 74% (SE 5 8%) in FUS-ERG, 0% (SE 5 0%) in RUNX1-CBFA2T3, compared with 32% (SE 5 1%) in the reference cohort (P < .001). Multivariate analysis identified both FUS-ERG and RUNX1-CBFA2T3 as independent risk factors with hazard ratios of 1.9 (P < .0001) and 0.3 (P 5 .025), respectively. These results describe 2 clinically relevant distinct subtypes of pediatric AML. Similarly to other core-binding factor AMLs, patients with RUNX1-CBFA2T3 rearranged AML may benefit from stratification in the standard risk treatment, whereas patients with FUS-ERG rearranged AML should be considered high-risk

Clinical Relevance of Dissolution Testing in Quality by Design

Quality by design (QbD) has recently been introduced in pharmaceutical product development in a regulatory context and the process of implementing such concepts in the drug approval process is presently on-going. This has the potential to allow for a more flexible regulatory approach based on understanding and optimisation of how design of a product and its manufacturing process may affect product quality. Thus, adding restrictions to manufacturing beyond what can be motivated by clinical quality brings no benefits but only additional costs. This leads to a challenge for biopharmaceutical scientists to link clinical product performance to critical manufacturing attributes. In vitro dissolution testing is clearly a key tool for this purpose and the present bioequivalence guidelines and biopharmaceutical classification system (BCS) provides a platform for regulatory applications of in vitro dissolution as a marker for consistency in clinical outcomes. However, the application of these concepts might need to be further developed in the context of QbD to take advantage of the higher level of understanding that is implied and displayed in regulatory documentation utilising QbD concepts. Aspects that should be considered include identification of rate limiting steps in the absorption process that can be linked to pharmacokinetic variables and used for prediction of bioavailability variables, in vivo relevance of in vitro dissolution test conditions and performance/interpretation of specific bioavailability studies on critical formulation/process variables. This article will give some examples and suggestions how clinical relevance of dissolution testing can be achieved in the context of QbD derived from a specific case study for a BCS II compound