Evidence for Multiple Phase Transitions in La_1-xCa_xCoO_3

We report thermal-expansion and specific-heat data of the series La_1-xCa_xCoO_3 for 0 <= x <= 0.3. For x = 0 the thermal-expansion coefficient alpha(T) features a pronounced maximum around T = 50 K caused by a temperature-dependent spin-state transition from a low-spin state (S=0) at low temperatures towards a higher spin state of the Co^3+ ions. The partial substitution of the La^3+ ions by divalent Ca^2+ ions causes drastic changes in the macroscopic properties of LaCoO_3. Around x ~ 0.125 the large maximum in alpha(T) has completely vanished. With further increasing x three different anomalies develop

Bacillus subtilis as heterologous host for the secretory production of the non-ribosomal cyclodepsipeptide enniatin

The heterologous expression of genes or gene clusters in microbial hosts, followed by metabolic engineering of biosynthetic pathways, is key to access industrially and pharmaceutically relevant compounds in an economically affordable and sustainable manner. Therefore, platforms need to be developed, which provide tools for the controlled synthesis of bioactive compounds. The Gram-positive bacterium Bacillus subtilis is a promising candidate for such applications, as it is generally regarded as a safe production host, its physiology is well investigated and a variety of tools is available for its genetic manipulation. Furthermore, this industrially relevant bacterium provides a high secretory potential not only for enzymes but also for primary and secondary metabolites. In this study, we present the first heterologous expression of an eukaryotic non-ribosomal peptide synthetase gene (esyn) coding for the biosynthesis of the small molecule enniatin in B. subtilis. Enniatin is a pharmaceutically used cyclodepsipeptide for treatment of topical bacterial and fungal infections. We generated various enniatin-producing B. subtilis strains, allowing for either single chromosomal or plasmid-based multi-copy expression of the esyn cluster under the control of an acetoin-inducible promoter system. Optimization of cultivation conditions, combined with modifications of the genetic background and multi-copy plasmid-based esyn expression, resulted in a secretory production of enniatin B. This work presents B. subtilis as a suitable host for the expression of heterologous eukaryotic non-ribosomal peptide synthetases (NRPS) clusters

Attention bias and anxiety in young children exposed to family violence

Background—Attention bias towards threat is associated with anxiety in older youth and adults and has been linked with violence exposure. Attention bias may moderate the relationship between violence exposure and anxiety in young children. Capitalizing on measurement advances, the current study examines these relationships at a younger age than previously possible. Methods—Young children (mean age 4.7, ±0.8) from a cross-sectional sample oversampled for violence exposure (N = 218) completed the dot-probe task to assess their attention biases. Observed fear/anxiety was characterized with a novel observational paradigm, the Anxiety Diagnostic Observation Schedule. Mother-reported symptoms were assessed with the Preschool-Age Psychiatric Assessment and Trauma Symptom Checklist for Young Children. Violence exposure was characterized with dimensional scores reflecting probability of membership in two classes derived via latent class analysis from the Conflict Tactics Scales: Abuse and Harsh Parenting. Results—Family violence predicted greater child anxiety and trauma symptoms. Attention bias moderated the relationship between violence and anxiety

Evidence for orbital ordering in LaCoO3

We present powder and single crystal X-ray diffraction data as evidence for a monoclinic distortion in the low spin (S=0) and intermediate spin state (S=1) of LaCoO3. The alternation of short and long bonds in the ab plane indicates the presence of eg orbital ordering induced by a cooperative Jahn-Teller distortion. We observe an increase of the Jahn-Teller distortion with temperature in agreement with a thermally activated behavior of the Co3+ ions from a low-spin ground state to an intermediate-spin excited state.Comment: Accepted to Phys. Rev.

Early magnesium reduction in advanced colorectal cancer patients treated with cetuximab plus irinotecan as predictive factor of efficacy and outcome

Introduction: Magnesium plays a role in a large number of cellular metabolic reactions. Cetuximab is able to induce hypomagnesemia by interfering with magnesium (Mg2+) transport in the kidney.We designed this trial to investigate if Mg2+ serum level modifications may be related with clinical response andoutcome in advancedcolorectal cancer patients during treatment with cetuximab plus irinotecan. Experimental Design: Sixty-eight heavily pretreatedmetastatic colorectal cancer patients were evaluatedfor Mg2+ serum levels at the following time points: before; 6 hours; and1, 7, 14, 21, 50, and92 days after the start of treatment. Results: Basal Mg2+ median levels were significantly decreased just 7 days after the first anticancer infusion and progressively decreased from the 7th day onward, reaching the highest significance at the last time point (P < 0.0001).Twenty-five patients showeda reduction in median Mg2+ circulating levels of at least 20% within the 3rdweek after the first infusion. Patients with this reduction showed a response rate of 64.0% versus 25.6% in the nonreduced Mg2+ group. The median time to progression was 6.0 versus 3.6 months in the reduced Mg2+ group andin that without reduction, respectively (P < 0.0001). Overall survival was longer in patients with Mg2+ reduction than in those without (10.7 versus 8.9 months). Conclusions: Our results confirm that cetuximab treatment may induce a reduction of Mg2+ circulating levels andoffer the first evidence that Mg2+ reduction may represent a new predictive factor of efficacy in advanced colorectal cancer patients treated with cetuximab plus irinoteca

Bevacizumab in association with de Gramont 5-fluorouracil/folinic acid in patients with oxaliplatin-, irinotecan-, and cetuximab-refractory colorectal cancer: a single-center phase 2 trial.

BACKGROUND: The aim of the current study was the investigation of the value of bevacizumab+5-fluorouracil(5-FU)/folinic acid in patients with advanced colorectal cancers who have exhausted standard chemotherapy options. METHODS: The authors included 48 heavily pretreated patients (colon:rectum, 33:15; men:women, 23:25; median age, 63 years; range, 27-79 years) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy, an irinotecan-based second-line regimen, and a third-line treatment with cetuximab plus weekly irinotecan. Bevacizumab was given at a dose of 5 mg/kg. 5-FU/folinic acid was administered according to the de Gramont schedule. RESULTS: The response rate was 6.25%, and 30.4% of patients demonstrated stable disease as the best response. The median time to disease progression was 3.5 months (95% confidence interval [95% CI], 2.3-6.9 months), and the median survival time was 7.7 months (95% CI, 3.9-11.9 months). The most common grade 3 to 4 side toxicities (graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) were: diarrhea (20.8%), fatigue (14.5%), and stomatitis (12.5%). Grade 3 to 4 hemorrhage occurred in 8 patients (16.6%), including 4 cases of bleeding in the gastrointestinal tract. Other relatively common adverse events such as hypertension, thrombosis, and bowel perforation were reported in 50%, 18.7%, and 4.16%, of patients respectively. CONCLUSIONS: The data from the current study suggest a modest but significant clinical benefit of bevacizumab+de Gramont schedule in heavily pretreated colorectal cancer patients. Copyright (c) 2009 American Cancer Society

Synchronization of multi-phase oscillators: An Axelrod-inspired model

Inspired by Axelrod's model of culture dissemination, we introduce and analyze a model for a population of coupled oscillators where different levels of synchronization can be assimilated to different degrees of cultural organization. The state of each oscillator is represented by a set of phases, and the interaction --which occurs between homologous phases-- is weighted by a decreasing function of the distance between individual states. Both ordered arrays and random networks are considered. We find that the transition between synchronization and incoherent behaviour is mediated by a clustering regime with rich organizational structure, where some of the phases of a given oscillator can be synchronized to a certain cluster, while its other phases are synchronized to different clusters.Comment: 6 pages, 5 figure

Developing European conservation and mitigation tools for pollination services: approaches of the STEP (Status and Trends of European Pollinators) project

Pollinating insects form a key component of European biodiversity, and provide a vital ecosystem service to crops and wild plants. There is growing evidence of declines in both wild and domesticated pollinators, and parallel declines in plants relying upon them. The STEP project (Status and Trends of European Pollinators, 2010-2015, www.stepproject.net) is documenting critical elements in the nature and extent of these declines, examining key functional traits associated with pollination deficits, and developing a Red List for some European pollinator groups. Together these activities are laying the groundwork for future pollinator monitoring programmes. STEP is also assessing the relative importance of potential drivers of pollinator declines, including climate change, habitat loss and fragmentation, agrochemicals, pathogens, alien species, light pollution, and their interactions. We are measuring the ecological and economic impacts of declining pollinator services and floral resources, including effects on wild plant populations, crop production and human nutrition. STEP is reviewing existing and potential mitigation options, and providing novel tests of their effectiveness across Europe. Our work is building upon existing and newly developed datasets and models, complemented by spatially-replicated campaigns of field research to fill gaps in current knowledge. Findings are being integrated into a policy-relevant framework to create evidence-based decision support tools. STEP is establishing communication links to a wide range of stakeholders across Europe and beyond, including policy makers, beekeepers, farmers, academics and the general public. Taken together, the STEP research programme aims to improve our understanding of the nature, causes, consequences and potential mitigation of declines in pollination services at local, national, continental and global scales

Specific heat and magnetization study on single crystals of a frustrated, quasi one-dimensional oxide: Ca3Co2O6

Specific heat and magnetization measurements have been carried out under a range of magnetic fields on single crystals of Ca3Co2O6. This compound is composed of Ising magnetic chains that are arranged on a triangular lattice. The intrachain and interchain couplings are ferromagnetic and antiferromagnetic, respectively. This situation gives rise to geometrical frustration, that bears some similarity to the classical problem of a two-dimensional Ising triangular antiferromagnet. This paper reports on the ordering process at low-T and the possibility of one-dimensional features at high-T.Comment: 7 pages, 6 figures, accepted for publication in PR