Universality of optimal measurements

We present optimal and minimal measurements on identical copies of an unknown state of a quantum bit when the quality of measuring strategies is quantified with the gain of information (Kullback-or mutual information-of probability distributions). We also show that the maximal gain of information occurs, among isotropic priors, when the state is known to be pure. Universality of optimal measurements follows from our results: using the fidelity or the gain of information, two different figures of merits, leads to exactly the same conclusions for isotropic distributions. We finally investigate the optimal capacity of N copies of an unknown state as a quantum channel of information.

Development of an Fn14 agonistic antibody as an anti-tumor agent.

TWEAK, a TNF family ligand with pleiotropic cellular functions, was originally described as capable of inducing tumor cell death in vitro. TWEAK functions by binding its receptor, Fn14, which is up-regulated on many human solid tumors. Herein, we show that intratumoral administration of TWEAK, delivered either by an adenoviral vector or in an immunoglobulin Fc-fusion form, results in significant inhibition of tumor growth in a breast xenograft model. To exploit the TWEAK-Fn14 pathway as a therapeutic target in oncology, we developed an anti-Fn14 agonistic antibody, BIIB036. Studies described herein show that BIIB036 binds specifically to Fn14 but not other members of the TNF receptor family, induces Fn14 signaling, and promotes tumor cell apoptosis in vitro. In vivo, BIIB036 effectively inhibits growth of tumors in multiple xenograft models, including colon (WiDr), breast (MDA-MB-231), and gastric (NCI-N87) tumors, regardless of tumor cell growth inhibition response observed to BIIB036 in vitro. The anti-tumor activity in these cell lines is not TNF-dependent. Increasing the antigen-binding valency of BIB036 significantly enhances its anti-tumor effect, suggesting the contribution of higher order cross-linking of the Fn14 receptor. Full Fc effector function is required for maximal activity of BIIB036 in vivo, likely due to the cross-linking effect and/or ADCC mediated tumor killing activity. Taken together, the anti-tumor properties of BIIB036 validate Fn14 as a promising target in oncology and demonstrate its potential therapeutic utility in multiple solid tumor indications.

Detrital zircon and micropalaeontological ages as new constraints for the lowermost tectonic unit (Talea Ori unit) of Crete, Greece

The Talea Ori unit is the lowermost known tectonic unit of Crete and the most external part of the Hellenides. Its stratigraphy ranges from Late Carboniferous to Oligocene and outcrops of the lower part are only known in the Talea Ori mountains (central Crete). In this area, a black sandstone at the base of the Galinos Beds, thought to be the oldest formation, contains zircons which were dated using the single grain evaporation method. The majority of these grains yielded Late Carboniferous ages (Variscan), while a small group yielded Early Proterozoic ages. The age distribution of these zircons suggests that, at the Carboniferous-Permian boundary, not much of the older North Gondwanan basement was exposed and that a river system carried detrital material from the Variscan belt towards the forming Neotethyan rift. Additionally, higher up in the stratigraphy benthic foraminifers (miliolids) were found in clasts from a conglomerate which was so far thought to be of Early Triassic age [Epting, M., Kudrass, H.-R., Leppig, U., Schaffer, A., 1972. Geologie der Talea Ori/Kreta. N. Jb. Geol. Palaont. Abh. 141, 259-285.]. These miliolids belong to the species Hoyenella inconstans [Michalik, J., Jendrejakova, O., Borza, K., 1979. Some new foraminifera species of the Fatra-Formation (Uppermost Triassic) in the West Carpathians. Geol. Carpath. 30 (1), 61-91.], thus attributing a Late Triassic (Carnian-Norian?) maximal age to this conglomerate. The carbonate platform from which the miliolids-bearing clasts come is not known. The presence to the north of a continuous hemipelagic record from the Carboniferous to the Triassic (Phyllite-Quartzite and Tripali units), attributed to the Palaeotethys realm, allows the Talea Ori unit and its lateral equivalents (the Ionian zone) to be assigned to the westward continuation of the Cimmerian block and therefore to the northern margin of the East Mediterranean Neotethys ocean. (c) 2006 Elsevier B.V. All rights reserved.

Fructose and glucose co-ingestion during prolonged exercise increases lactate and glucose fluxes and oxidation compared with an equimolar intake of glucose

BACKGROUND: When fructose is ingested together with glucose (GLUFRU) during exercise, plasma lactate and exogenous carbohydrate oxidation rates are higher than with glucose alone. OBJECTIVE: The objective was to investigate to what extent GLUFRU increased lactate kinetics and oxidation rate and gluconeogenesis from lactate (GNG(L)) and from fructose (GNG(F)). DESIGN: Seven endurance-trained men performed 120 min of exercise at approximately 60% VOmax (maximal oxygen consumption) while ingesting 1.2 g glucose/min + 0.8 g of either glucose or fructose/min (GLUFRU). In 2 trials, the effects of glucose and GLUFRU on lactate and glucose kinetics were investigated with glucose and lactate tracers. In a third trial, labeled fructose was added to GLUFRU to assess fructose disposal. RESULTS: In GLUFRU, lactate appearance (120 +/- 6 mumol . kg(1) . min(1)), lactate disappearance (121 +/- 7 mumol . kg(1) . min(1)), and oxidation (127 +/- 12 mumol . kg(1) . min(1)) rates increased significantly (P < 0.001) in comparison with glucose alone (94 +/- 16, 95 +/- 16, and 97 +/- 16 mumol . kg(1) . min(1), respectively). GNG(L) was negligible in both conditions. In GLUFRU, GNG(F) and exogenous fructose oxidation increased with time and leveled off at 18.8 +/- 3.7 and 38 +/- 4 mumol . kg(1) . min(1), respectively, at 100 min. Plasma glucose appearance rate was significantly higher (P < 0.01) in GLUFRU (91 +/- 6 mumol . kg(1) . min(1)) than in glucose alone (82 +/- 9 mumol . kg(1) . min(1)). Carbohydrate oxidation rate was higher (P < 0.05) in GLUFRU. CONCLUSIONS: Fructose increased total carbohydrate oxidation, lactate production and oxidation, and GNG(F). Fructose oxidation was explained equally by fructose-derived lactate and glucose oxidation, most likely in skeletal and cardiac muscle. This trial was registered at clinicaltrials.gov as NCT01128647.

Three-party entanglement from positronium

The decay of orthopositronium into three photons produces a physical realization of a pure state with three-party entanglement. Its quantum correlations are analyzed using recent results on quantum information theory, looking for the final state that has the maximal amount of Greenberger, Horne, and Zeilinger like correlations. This state allows for a statistical dismissal of local realism stronger than the one obtained using any entangled state of two spin one-half particles.

Pairing in two-dimensional boson-fermion mixtures

The possibilities of pairing in two-dimensional boson-fermion mixtures are carefully analyzed. It is shown that the boson-induced attraction between two identical fermions dominates the p wave pairing at low density. For a given fermion density, the pairing gap becomes maximal at a certain optimal boson concentration. The conditions for observing pairing in current experiments are discussed.

Familiality and SNP heritability of age at onset and episodicity in major depressive disorder.

BACKGROUND: Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability). METHOD: For investigating familiality, we used 691 families with 2-5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software. RESULTS: Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity. CONCLUSIONS: AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.

Intrauterine growth restriction is associated with structural alterations in human umbilical cord and decreased nitric oxide-induced relaxation of umbilical vein.

INTRODUCTION: Intrauterine growth restriction (IUGR) affects ∼8% of all pregnancies and is associated with major perinatal mortality and morbidity, and with an increased risk to develop cardiovascular diseases in adulthood. Despite identification of several risk factors, the mechanisms implicated in the development of IUGR remain poorly understood. In case of placental insufficiency, reduced delivery of oxygen and/or nutrients to the fetus could be associated with alterations in the umbilical circulation, contributing further to the impairment of maternal-fetal exchanges. We compared the structural and functional properties of umbilical cords from growth-restricted and appropriate for gestational age (AGA) term newborns, with particular attention to the umbilical vein (UV). METHODS: Human umbilical cords were collected at delivery. Morphological changes were investigated by histomorphometry, and UV's reactivity by pharmacological studies. RESULTS: Growth-restricted newborns displayed significantly lower growth parameters, placental weight and umbilical cord diameter than AGA controls. Total cross-section and smooth muscle areas were significantly smaller in UV of growth-restricted neonates than in controls. Maximal vasoconstriction achieved in isolated UV was lower in growth-restricted boys than in controls, whereas nitric oxide-induced relaxation was significantly reduced in UV of growth-restricted girls compared to controls. CONCLUSION: IUGR is associated with structural alterations of the UV in both genders, and with a decreased nitric oxide-induced relaxation in UV of newborn girls, whereas boys display impaired vasoconstriction. Further investigations will allow to better understand the regulation of umbilical circulation in growth-restricted neonates, which could contribute to devise potential novel therapeutic strategies to prevent or limit the development of IUGR.