Local uncertainty relations serving as measures of entanglement in a bipartite two-level system

We comment on the recent suggestion to use a family of local uncertainty relations as a standard way of quantifying entanglement in two-qubit systems. Some statements made on the applicability of the proposed "measures" are overly optimistic. We exemplify how these specific "measures" fall short, and present a minor modification of the general theory which uses the same experimentally gathered information, but in a slightly different, better way.Comment: 5 pages, 1 figur

Система экономического стимулирования персонала предприятия (на примере ГЛХУ «Милошевичский лесхоз»)

The load in the electricity grid fluctuates during the day and between seasons. As a distribution system operator (DSO), an uneven load profile leads to increased transmission losses and unnecessary high costs for subscribing power from the feeding grid. Efficiency measures and a more even power consumption by the end-users, could therefore lead to that a DSO can achieve lower costs for power-subscription from the feeding grid and transmission losses, but also implies a lowered cap of total revenues. As a step towards implementing the EU energy efficiency directive, the Energy Markets Inspectorate (Ei) have developed two economic incentives which enables for DSOs to profit economically from cost reductions related to transmission losses and feeding grid. For this reason the electricity suppliers Storuman Energi and Affärsverken Energi sees a possibility to offer a load shift-service to low voltage DSOs using the flexibility in the demand of electrically heated households. The aim of this study is therefore to demonstrate how a service such as this one can be valued in the Swedish electricity market. The task at hand was examined by conducting a survey of the values of demand-side flexibility, as well as an investigation of how the costs for the end-user and incentives for the DSO are affected by flexibility. A review of the values associated with demand-side flexibility has been conducted for electricity suppliers, DSOs and end-users. With regard to the DSOs, the main value is connected to the new economic incentives from Ei, whose potential depends on the properties of the grid and the tariff for the feeding grid. Other values related to operation and delivery reliability can also be achieved. The main values for electricity suppliers are a lowered risk for unbalance following as a consequence of better knowledge of their end-users’ usage, and also the possibility to profit by offering a load shift-service. The values for end-users have been divided between cost reductions and system benefits, both of which are regarded to compensate the remuneration end-users require to offer their flexibility. By adapting consumption after the spot market price or the grid tariff, lowered costs for electricity can be achieved. The end-users can also appreciate system-benefits such as the facilitation for intermittent renewable electricity production, electric vehicles and reducing the societal dependency on expensive fossil-fuelled power generation as positive. They do on the other hand regard a possible depreciation of the heat comfort, data confidentiality and reduced control over one’s own electricity consumption as negative. If the service can be bundled with equipment which yields other values, such as an increased heat comfort, the end-users’ demand for remuneration can decrease. To explore what effects demand-side flexibility can have on the electricity costs of end-users and the economic incentives for DSOs, a case study is conducted in the electricity distribution grid of Karlskrona. Through review of previous studies, a potential for demand reductions was established and used as input in the case study. It can be determined that the incentive for a more even load profile constitutes a substantially greater share of the total incentives, compared to the incentive for reduced distribution losses. It is further concluded that a fairly large part of the incentives can be achieved by controlling the end-users on only a few occasions each year. It is also established that the cost reductions for end-users can match their demand for remuneration. A future scenario with more electrical vehicles connected to the grid for charging, greatly increases the possible benefits for both the DSO and end-users. Through the investigation of different possible designs for the energy service, it is recommended that the demand side management of end-users is placed in the hands of an electricity supplier responsible for balancing the consumption of the end-users. A procurement-procedure is deemed problematicfollowing the risk for unproportional use of resources and time. As a result of this, the energy service should not be traded directly between DSOs and electricity suppliers. Instead, it is proposed that the DSO develops a time-differentiated tariff, after which the electricity supplier can adapt the end-users’ consumption. Since the results indicate that controlling the end-users consumption on just a few occasions is sufficient to yield large benefits for the DSO, a grid-tariff with critical peak pricing is recommended. This tariff employs a high price for shorter periods of time when the grid load is peaking and a rebated price during all other occasions. This opens up for controlling the use during the other days according to the spot market price. As the electricity supplier grants the end-user lowered costs for both the electricity grid and trading, they have the opportunity to apply a charge for the service. Both the DSO, end-user and electricity supplier is presumed to improve their profitability with this design. When implementing the energy service, a couple of aspects are important to shed light on. The grid-tariff of the end-user and the tariff for the feeding grid needs to be synchronized with each other, to stimulate the same type of load shifts. It should also be noted that the possible gain from the incentives will decrease as demand side management-measures is taken since the reference-level from which a comparison is made improves. Another interesting aspect is that the regulation stipulates that only a certain percentage of the cost reductions will result in incentives, thus limiting the amount of profitable measures. Since the costs and revenues between the actors in the transmission system (low and medium voltage DSOs and the TSO) are interdependent, the revenue loss for the medium voltage DSO resulting from the cost reduction for the low voltage DSO, can result in a recoil effect. Lastly, a widespread introduction of control equipment to end-users can facilitate other uses for the demand-side flexibility.Belastningen i elnätet varierar under dagen och mellan olika säsonger. Att som nätägare ha en ojämn belastning i sitt nät leder till ökade nätförluster och onödigt höga kostnader för att abonnera effekt från det överliggande nätet. Effektiviseringar i nätet och ett jämnare effektuttag av användarna kan därmed leda till att en nätägare kan erhålla minskade kostnader för abonnerad effekt från överliggande nät och nätförluster, men innebär också en sänkt intäktsram för nätägaren. Vid implementering av EU:s energieffektiviseringsdirektiv har Energimarknadsinspektionen tagit fram två ekonomiska incitament som möjliggör för nätägare att dra nytta av kostnadsminskningar för nätförluster och överliggande nät. Av denna anledning ser elhandelsbolagen Storuman Energi och Affärsverken Energi möjligheter att, med hjälp av efterfrågeflexibilitet hos framförallt eluppvärmda hushåll, erbjuda en laststyrningstjänst till lokalnätsnätägare. Syftet med denna studie är därmed att demonstrera hur en tjänst som denna kan värdesättas av aktörerna på den svenska elmarknaden. Frågan behandlas genom att undersöka vilka värden efterfrågeflexibilitet kan ge upphov till, exempelvis hur slutanvändares elkostnader och nätägares ekonomiska incitament påverkas av efterfrågeflexibilitet. En inventering har gjorts av efterfrågeflexibilitetens värde för elhandlare, nätägare och slutanvändare. För nätägare bedöms de huvudsakliga värdena finnas kring de nya ekonomiska incitamenten, vars potential beror på nätets förutsättningar och regionnätstariffen. Det finns också nyttor kopplade till driftsäkerhet och leveranskvalitet. Elhandlare kan dra nytta av en lägre risk för obalans genom att de får bättre uppfattning om sina kunders användningsmönster, samt möjligheten att även debitera för utförd laststyrningstjänst. För slutanvändare har värdena delats upp i kostnadsminskningar och systemnyttor. Båda dessa anses kunna kompensera för de krav på ersättning som slutanvändare har för att bidra med sin flexibilitet. Genom anpassning efter exempelvis spotpris eller en nättariff kan lägre kostnader för elhandel respektive nät erhållas. Vad gäller systemnyttor kan följder som att exempelvis främja intermittent förnybar elproduktion, underlätta införande av en eldriven fordonsflotta samt att minska beroendet av dyra fossileldade produktionsslag ses som positiva. Å andra sidan bedöms en upplevd risk för försämrad värmekomfort och datasekretess samt minskad kontroll över sin användning spela in som negativa värden. Om tjänsten kan paketeras tillsammans med utrustning som även ger andra mervärden, exempelvis möjliggör en ökad värmekomfort, kan slutanvändares ersättningskrav minska. För att utreda vilken konkret påverkan efterfrågeflexibilitet kan ha på slutanvändares elkostnader och nätägares ekonomiska incitament görs en undersökning i Karlskronas lokalnät. Där appliceras den potential för efterfrågeflexibilitet som tidigare studier visat på. Det konstateras att incitamentet för jämnare nätbelastning visar betydligt större potential än det för minskade nätförluster samt att en stor del av incitamenten går att erhålla genom att styra endast ett fåtal tillfällen varje år. Vidare pekar resultatet på att slutanvändares kostnadsminskningar kan nå upp i nivåer som motsvarar deras ersättningskrav. Ett framtidsscenario med fler elfordon ger mycket större ekonomisk potential för både nätägare och slutanvändare. Efter att ha utrett olika alternativa utformningar för energitjänsten föreslås att passiv efterfrågeflexibilitet tillämpas genom att laststyrning av slutanvändare sker av en elhandlande aggregator med balansansvar. Ett upphandlingsförfarande bedöms medföra risk för stor resurs- och tidsåtgång, varför handel av tjänsten inte bör äga rum mellan elhandlare och nätägare. Men för att elhandlare ändå ska kunna ta del av värdet från de ekonomiska incitamenten föreslås att nätägaren tar fram en tidsdifferentierad nättariff, vilken elhandlaren kan laststyra slutanvändare efter. Då resultatet pekar på att styrning under endast ett fåtal tillfällen är erforderligt kan en nättariff av typen spetspristariff tillämpas, där kostnaden för effektuttag kraftigt stiger när belastningen är hög i nätet. Då möjliggörs styrning efter exempelvis spotpris de tillfällen som inte är nödvändiga att styra med hänsyn till nätet, eftersom kostnaden för effektuttag då är låg. Genom att elhandlare på så sätt kan erbjuda slutanvändare lägre kostnader för både nät och elhandel har de möjlighet att debitera slutanvändare en avgift för utförd tjänst. Med denna utformning anses både nätägare, elhandlare och slutanvändare kunna nå en ökad lönsamhet. Vid införandet av energitjänsten är ett antal aspekter viktiga att belysa. Slutanvändares nättariff och lokalnätets tariff för överliggande nät spelar en viktig roll då de behöver stimulera till att samma styrning utförs, exempelvis om det är fördelaktigt att styrning sker ofta eller mer sällan. Då incitamentens nivå bestäms utifrån en referensperiod kommer möjlig avkastning att avta i takt med att förbättringar görs. I nätregleringen är det fastställt att bara en viss del av kostnadsbesparingarna erhålls i form av de ekonomiska incitamenten, vilket innebär att vilka åtgärder som är lönsamma begränsas. Genom att kostnader och intäkter är tätt sammankopplade mellan aktörerna i elnätet (lokal-, region- och stamnät) kan regionnätets intäktsbortfall till följd av lokalnätets lägre kostnader, ge upphov till rekyleffekter. Att storskaligt installera styrutrustning hos slutanvändare kan också möjliggöra andra användningsområden, med andra ord skapas det en plattform för efterfrågeflexibilitet

Mutations in PROSC Disrupt Cellular Pyridoxal Phosphate Homeostasis and Cause Vitamin B6-Dependent Epilepsy

Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, functions as a cofactor in humans for more than 140 enzymes, many of which are involved in neurotransmitter synthesis and degradation. A deficiency of PLP can present, therefore, as seizures and other symptoms which are treatable with PLP and/or pyridoxine. Deficiency of PLP in the brain can be caused by inborn errors affecting B6 vitamer metabolism or by inactivation of PLP; by compounds accumulating as a result of inborn errors of other pathways or by ingested small molecules. Whole exome sequencing of 2 children from a consanguineous family with pyridoxine-dependent epilepsy revealed a homozygous nonsense mutation in proline synthetase co-transcribed homolog (bacterial) (PROSC), a PLPbinding protein of hitherto unknown function. Subsequent sequencing of 29 unrelated indivduals with pyridoxine-responsive epilepsy identified 4 additional children with biallelic PROSC mutations. Pretreatment cerebrospinal fluid samples showed low PLP concentrations and evidence of reduced activity of PLP-dependent enzymes. However, cultured fibroblasts showed excessive PLP accumulation. An E.coli mutant, lacking the PROSC homologue (ΔYggS) is pyridoxine-sensitive; complementation with human PROSC restored growth whilst hPROSC bearing p.Leu175Pro, p.Arg241Gln and p.Ser78Ter did not. PLP, a highly reactive aldehyde, poses a problem for cells - how to supply enough PLP for apoenzymes while maintaining free PLP concentrations low enough to avoid unwanted reactions with other important cellular nucleophiles. Whilst the mechanism involved is not fully understood our studies suggest that PROSC is involved in intracellular homeostatic regulation of PLP, supplying this cofactor to apoenzymes while minimizing any toxic side reactions

Molecular and Biological Characterization of the Murine Leukotriene B4 Receptor Expressed on Eosinophils

The movement of leukocytes into tissues is regulated by the local production of chemical mediators collectively referred to as chemoattractants. Although chemoattractants constitute a diverse array of molecules, including proteins, peptides, and lipids, they all appear to signal leukocytes through a related family of seven transmembrane–spanning G protein–coupled receptors. The eosinophil is a potent proinflammatory cell that is attracted into tissues during allergic inflammation, parasitic infection, and certain malignancies. Since the molecular mechanisms controlling eosinophil recruitment are incompletely understood, we performed a degenerate polymerase chain reaction on cDNA isolated from murine eosinophils to identify novel chemoattractant receptors. We report the isolation of a cDNA that encodes a 351–amino acid glycoprotein that is 78% identical to a human gene that has been reported to be a purinoceptor (P2Y7) and a leukotriene B4 (LTB4) receptor (BLTR). Chinese hamster ovary (CHO) cells transfected with this cDNA specifically bound [3H]LTB4 with a dissociation constant of 0.6 ± 0.1 nM. Furthermore, LTB4 induced a dose-dependent intracellular calcium flux in transfected CHO cells. In contrast, [35S]dATP did not specifically bind to these transfectants. This mRNA was expressed at high levels in interleukin 5–exposed eosinophils, elicited peritoneal macrophages and neutrophils, and to a lesser extent interferon γ stimulated macrophages. Low levels of expression were detected in the lung, lymph node, and spleen of unchallenged mice. Western blot analysis detected the mBLTR protein in murine eosinophils and alveolar macrophages as well as human eosinophils. In addition, elevated levels of mBLTR mRNA were found in the lungs of mice in a murine model of allergic pulmonary inflammation in a time course consistent with the influx of eosinophils. Our findings indicate that this murine receptor is an LTB4 receptor that is highly expressed on activated leukocytes, including eosinophils, and may play an important role in mediating eosinophil recruitment into inflammatory foci

RNAcentral: A vision for an international database of RNA sequences

During the last decade there has been a great increase in the number of noncoding RNA genes identified, including new classes such as microRNAs and piRNAs. There is also a large growth in the amount of experimental characterization of these RNA components. Despite this growth in information, it is still difficult for researchers to access RNA data, because key data resources for noncoding RNAs have not yet been created. The most pressing omission is the lack of a comprehensive RNA sequence database, much like UniProt, which provides a comprehensive set of protein knowledge. In this article we propose the creation of a new open public resource that we term RNAcentral, which will contain a comprehensive collection of RNA sequences and fill an important gap in the provision of biomedical databases. We envision RNA researchers from all over the world joining a federated RNAcentral network, contributing specialized knowledge and databases. RNAcentral would centralize key data that are currently held across a variety of databases, allowing researchers instant access to a single, unified resource. This resource would facilitate the next generation of RNA research and help drive further discoveries, including those that improve food production and human and animal health. We encourage additional RNA database resources and research groups to join this effort. We aim to obtain international network funding to further this endeavor

Exposure of neonatal rats to maternal cafeteria feeding during suckling alters hepatic gene expression and DNA methylation in the insulin signalling pathway

Nutrition in early life is a determinant of lifelong physiological and metabolic function. Diseases that are associated with ageing may, therefore, have their antecedents in maternal nutrition during pregnancy and lactation. Rat mothers were fed either a standard laboratory chow diet (C) or a cafeteria diet (O) based upon a varied panel of highly palatable human foods, during lactation. Their offspring were then weaned onto chow or cafeteria diet giving four groups of animals (CC, CO, OC, OO n=9-10). Livers were harvested 10 weeks post-weaning for assessment of gene and protein expression, and DNA methylation. Cafeteria feeding post-weaning impaired glucose tolerance and was associated with sex-specific altered mRNA expression of peroxisome proliferator activated receptor gamma (PPARg) and components of the insulin-signalling pathway (Irs2, Akt1 and IrB). Exposure to the cafeteria diet during the suckling period modified the later response to the dietary challenge. Post-weaning cafeteria feeding only down-regulated IrB when associated with cafeteria feeding during suckling (group OO, interaction of diet in weaning and lactation P=0.041). Responses to cafeteria diet during both phases of the experiment varied between males and females. Global DNA methylation was altered in the liver following cafeteria feeding in the post-weaning period, in males but not females. Methylation of the IrB promoter was increased in group OC, but not OO (P=0.036). The findings of this study add to a growing evidence base that suggests tissue function across the lifespan a product of cumulative modifications to the epigenome and transcriptome, which may be both tissue and sex-specific

ADAM33, a New Candidate for Psoriasis Susceptibility

Psoriasis is a chronic skin disorder with multifactorial etiology. In a recent study, we reported results of a genome-wide scan on 46 French extended families presenting with plaque psoriasis. In addition to unambiguous linkage to the major susceptibility locus PSORS1 on Chromosome 6p21, we provided evidence for a susceptibility locus on Chromosome 20p13. To follow up this novel psoriasis susceptibility locus we used a family-based association test (FBAT) for an association scan over the 17 Mb candidate region. A total of 85 uncorrelated SNP markers located in 65 genes of the region were initially investigated in the same set of large families used for the genome wide search, which consisted of 295 nuclear families. When positive association was obtained for a SNP, candidate genes nearby were explored more in detail using a denser set of SNPs. Thus, the gene ADAM33 was found to be significantly associated with psoriasis in this family set (The best association was on a 3-SNP haplotype P = 0.00004, based on 1,000,000 permutations). This association was independent of PSORS1. ADAM33 has been previously associated with asthma, which demonstrates that immune system diseases may be controlled by common susceptibility genes with general effects on dermal inflammation and immunity. The identification of ADAM33 as a psoriasis susceptibility gene identified by positional cloning in an outbred population should provide insights into the pathogenesis and natural history of this common disease

Differential Inhibitory Effects of CysLT1 Receptor Antagonists on P2Y6 Receptor-Mediated Signaling and Ion Transport in Human Bronchial Epithelia

BACKGROUND: Cysteinyl leukotriene (CysLT) is one of the proinflammatory mediators released by the bronchi during inflammation. CysLTs exert their biological effects via specific G-protein-coupled receptors. CysLT(1) receptor antagonists are available for clinical use for the treatment of asthma. Recently, crosstalk between CysLT(1) and P2Y(6) receptors has been delineated. P2Y receptors are expressed in apical and/or basolateral membranes of virtually all polarized epithelia to control the transport of fluid and electrolytes. Previous research suggests that CysLT(1) receptor antagonists inhibit the effects of nucleotides acting at P2Y receptors. However, the detailed molecular mechanism underlying the inhibition remains unresolved. METHODOLOGY/PRINCIPAL FINDINGS: In this study, western blot analysis confirmed that both CysLT(1) and P2Y(6) receptors were expressed in the human bronchial epithelial cell line 16HBE14o-. All three CysLT(1) antagonists inhibited the uridine diphosphate (UDP)-evoked I(SC), but only montelukast inhibited the UDP-evoked [Ca(2+)](i) increase. In the presence of forskolin or 8-bromoadenosine 3'5' cyclic monophosphate (8-Br-cAMP), the UDP-induced I(SC) was potentiated but was reduced by pranlukast and zafirlukast but not montelukast. Pranlukast inhibited the UDP-evoked I(SC) potentiated by an Epac activator, 8-(4-Chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (8-CPT-2'-O-Me-cAMP), while montelukast and zafirlukast had no such effect. Pranlukast inhibited the real-time increase in cAMP changes activated by 8-CPT-2'-O-Me-cAMP as monitored by fluorescence resonance energy transfer imaging. Zafirlukast inhibited the UDP-induced I(SC) potentiated by N(6)-Phenyladenosine-3',5'-cyclic monophosphorothioate, Sp-isomer (Sp-6-Phe-cAMP; a PKA activator) and UDP-activated PKA activity. CONCLUSIONS/SIGNIFICANCE: In summary, our data strongly suggest for the first time that in human airway epithelia, the three specific CysLT(1) receptor antagonists exert differential inhibitory effects on P2Y(6) receptor-coupled Ca(2+) signaling pathways and the potentiating effect on I(SC) mediated by cAMP and Epac, leading to the modulation of ion transport activities across the epithelia

Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5

Coronary artery disease (CAD), and one of its intermediate risk factors, dyslipidemia, possess a demonstrable genetic component, although the genetic architecture is incompletely defined. We previously reported a linkage peak on chromosome 5q31-33 for early-onset CAD where the strength of evidence for linkage was increased in families with higher mean low density lipoprotein-cholesterol (LDL-C). Therefore, we sought to fine-map the peak using association mapping of LDL-C as an intermediate disease-related trait to further define the etiology of this linkage peak. The study populations consisted of 1908 individuals from the CATHGEN biorepository of patients undergoing cardiac catheterization; 254 families (N = 827 individuals) from the GENECARD familial study of early-onset CAD; and 162 aorta samples harvested from deceased donors. Linkage disequilibrium-tagged SNPs were selected with an average of one SNP per 20 kb for 126.6-160.2 MB (region of highest linkage) and less dense spacing (one SNP per 50 kb) for the flanking regions (117.7-126.6 and 160.2-167.5 MB) and genotyped on all samples using a custom Illumina array. Association analysis of each SNP with LDL-C was performed using multivariable linear regression (CATHGEN) and the quantitative trait transmission disequilibrium test (QTDT; GENECARD). SNPs associated with the intermediate quantitative trait, LDL-C, were then assessed for association with CAD (i.e., a qualitative phenotype) using linkage and association in the presence of linkage (APL; GENECARD) and logistic regression (CATHGEN and aortas)