Phragmén–Lindelöf Principles for Generalized Analytic Functions on Unbounded Domains

We prove versions of the Phragmén–Lindelöf strong maximum principle for generalized analytic functions defined on unbounded domains. A version of Hadamard’s three-lines theorem is also derived

Assessing the role of CAP for more sustainable and healthier food systems in Europe:A literature review

Today, the European food system is characterized by unhealthy dietary trends, environmentally unsustainable production, and a dependency on an ageing farming population. The ongoing reform of the Common Agricultural Policy (CAP) represents an opportunity to redress these issues. This literature review highlights trends in how academic and grey literature have received CAP attempts in addressing the (i) environmental issues, (ii) nutritional outcomes, and (iii) rural livelihoods. Additionally, future policy and research directions relating to the CAP have been identified from the selected literature. The reviewed literature varies in approach and perspective. In particular, since the environment and rural development are already part of the CAP, the reviewed studies analyze and propose improvements to existing mechanisms. While for nutrition, the reviewed studies assessed possible policy strategies for integrating this sphere within the CAP, highlighting both the complexity of this task as well as its potential benefits. Despite these differences, a clear commonality emerged from the policy recommendations: the CAP should promote the European Union (EU) policy integration and multi-disciplinary and participatory research as key strategies to meet food system sustainability targets.</p

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 9, Revision 4 (FGE.09Rev4): Secondary alicyclic saturated and unsaturated alcohols, ketones and esters containing secondary alicyclic alcohols from chemical group 8 and 30, and an ester of a phenol derivative from chemical group 25

&lt;p&gt;The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 21 flavouring substances in the Flavouring Group Evaluation 9, Revision 4, using the Procedure in Commission Regulation (EC) No 1565/2000. The present revision of FGE.09 includes the assessment of four additional flavouring substances, p-menthan-3-one [FL-no: 07.059], 2,6,6-trimethylcyclohex-2-en-1-one [FL-no: 07.202], l-piperitone [FL-no: 07.255] and menthol 1-and 2-propylene glycol carbonate [FL-no: 09.843]. None of the substances were considered to have genotoxic potential. The substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern, and available data on metabolism and toxicity. The Panel concluded that the 20 substances [FL-no: 02.070, 02.075, 02.135, 02.167, 06.136, 07.059, 07.202, 07.203, 07.255, 09.154, 09.355, 09.520, 09.618, 09.619, 09.621, 09.843, 09.870, 09.929, 09.935 and 09.949] do not give rise to safety concerns at their levels of dietary intake, estimated on the basis of the MSDI approach. For the remaining candidate substance [FL-no: 07.207], additional toxicity data are requested (further metabolism and/or toxicity studies). Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have been considered. Specifications including complete purity criteria and identity for the materials of commerce have been provided for all candidate substances.&lt;/p&gt

Copper Chaperone for Cu/Zn Superoxide Dismutase is a sensitive biomarker of mild copper deficiency induced by moderately high intakes of zinc

BACKGROUND: Small increases in zinc (Zn) consumption above recommended amounts have been shown to reduce copper (Cu) status in experimental animals and humans. Recently, we have reported that copper chaperone for Cu/Zn superoxide dismutase (CCS) protein level is increased in tissues of overtly Cu-deficient rats and proposed CCS as a novel biomarker of Cu status. METHODS: Weanling male Wistar rats were fed one of four diets normal in Cu and containing normal (30 mg Zn/kg diet) or moderately high (60, 120 or 240 mg Zn/kg diet) amounts of Zn for 5 weeks. To begin to examine the clinical relevance of CCS, we compared the sensitivity of CCS to mild Cu deficiency, induced by moderately high intakes of Zn, with conventional indices of Cu status. RESULTS: Liver and erythrocyte CCS expression was significantly (P < 0.05) increased in rats fed the Zn-60 and/or Zn-120 diet compared to rats fed normal levels of Zn (Zn-30). Erythrocyte CCS expression was the most sensitive measure of reduced Cu status and was able to detect a decrease in Cu nutriture in rats fed only twice the recommended amount of Zn. Liver, erythrocyte and white blood cell CCS expression showed a significant (P < 0.05) inverse correlation with plasma and liver Cu concentrations and caeruloplasmin activity. Unexpectedly, rats fed the highest level of Zn (Zn-240) showed overall better Cu status than rats fed a lower level of elevated Zn (Zn-120). Improved Cu status in these rats correlated with increased duodenal mRNA expression of several Zn-trafficking proteins (i.e. MT-1, ZnT-1, ZnT-2 and ZnT-4). CONCLUSION: Collectively, these data show that CCS is a sensitive measure of Zn-induced mild Cu deficiency and demonstrate a dose-dependent biphasic response for reduced Cu status by moderately high intakes of Zn

Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

Atypical disengagement from faces and its modulation by the control of eye fixation in children with Autism Spectrum Disorder

By using the gap overlap task, we investigated disengagement from faces and objects in children (9–17 years old) with and without autism spectrum disorder (ASD) and its neurophysiological correlates. In typically developing (TD) children, faces elicited larger gap effect, an index of attentional engagement, and larger saccade-related event-related potentials (ERPs), compared to objects. In children with ASD, by contrast, neither gap effect nor ERPs differ between faces and objects. Follow-up experiments demonstrated that instructed fixation on the eyes induces larger gap effect for faces in children with ASD, whereas instructed fixation on the mouth can disrupt larger gap effect in TD children. These results suggest a critical role of eye fixation on attentional engagement to faces in both groups

The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K

Molecular glue compounds induce protein-protein interactions that, in the context of a ubiquitin ligase, lead to protein degradation1. Unlike traditional enzyme inhibitors, these molecular glue degraders act substoichiometrically to catalyse the rapid depletion of previously inaccessible targets2. They are clinically effective and highly sought-after, but have thus far only been discovered serendipitously. Here, through systematically mining databases for correlations between the cytotoxicity of 4,518 clinical and preclinical small molecules and the expression levels of E3 ligase components across hundreds of human cancer cell lines3-5, we identify CR8-a cyclin-dependent kinase (CDK) inhibitor6-as a compound that acts as a molecular glue degrader. The CDK-bound form of CR8 has a solvent-exposed pyridyl moiety that induces the formation of a complex between CDK12-cyclin K and the CUL4 adaptor protein DDB1, bypassing the requirement for a substrate receptor and presenting cyclin K for ubiquitination and degradation. Our studies demonstrate that chemical alteration of surface-exposed moieties can confer gain-of-function glue properties to an inhibitor, and we propose this as a broader strategy through which target-binding molecules could be converted into molecular glues

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF) ; Scientific Opinion on Flavouring Group Evaluation 06, Revision 4 (FGE.06Rev4 ): Straight - and branched - chain aliphatic unsaturated primary alcohols, aldehydes, carboxylic acids and esters from chemical groups 1, 3 and 4

The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 56 flavouring substances in the Flavouring Group Evaluation 6, Revision 4, using the Procedure in Commission Regulation (EC) No 1565/2000. This revision is made due to the inclusion of six additional flavouring substances, (-)-3,7-dimethyl-6-octen-1-ol [FL-no: 02.229], dec-4(cis)-enal [FL-no: 05.137], neral [FL-no: 05.170], trans-3,7-dimethylocta-2,6-dienal (geranial) [FL-no: 05.188], trans-3-hexenyl formate [FL-no: 09.562] and cis-3-hexenyl 2-methylbutanoate [FL-no: 09.854]. None of the substances were considered to have genotoxic potential. The substances were evaluated through a stepwise approach (the Procedure) that integrates information on structure-activity relationships, intake from current uses, toxicological threshold of concern and available data on metabolism and toxicity. The Panel concluded that the 56 substances [FL-no: 02.125, 02.138, 02.152, 02.170, 02.175, 02.176, 02.195, 02.201, 02.222, 02.229, 02.234, 05.061, 05.082, 05.137, 05.143, 05.170, 05.174, 05.188, 05.203, 05.217, 05.218, 05.220, 05.226, 08.074, 08.100, 08.102, 09.341, 09.368, 09.377, 09.562, 09.567, 09.569, 09.572, 09.575, 09.612, 09.638, 09.640, 09.643, 09.672, 09.673, 09.674, 09.831, 09.838, 09.854, 09.855, 09.871, 09.872, 09.884, 09.885, 09.897, 09.898, 09.928, 09.937, 09.938, 09.939 and 09.950] do not give rise to safety concern at their levels of dietary intake, estimated on the basis of the MSDI approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered. Adequate specifications including complete purity criteria and identity for the materials of commerce have been provided for all 56 candidate substances