Delayed-Choice Experiments and the Metaphysics of Entanglement

Delayed-choice experiments in quantum mechanics are often taken to undermine a realistic interpretation of the quantum state. More specifically, Healey has recently argued that the phenomenon of delayed-choice entanglement swapping is incompatible with the view that entanglement is a physical relation between quantum systems. This paper argues against these claims. It first reviews two paradigmatic delayed-choice experiments and analyzes their metaphysical implications. It then applies the results of this analysis to the case of entanglement swapping, showing that such experiments pose no threat to realism about entanglement.

Molecular characterization of HLA-C incompatibilities in HLA-ABDR-matched unrelated bone marrow donor-recipient pairs. Sequence of two new Cw alleles (Cw*02023 and Cw*0707) and recognition by cytotoxic T lymphocytes.

While the influence of HLA-AB and -DRB1 matching on the outcome of bone marrow transplantation (BMT) with unrelated donors is clear, the evaluation of HLA-C has been hampered by its poor serological definition. Because the low resolution of standard HLA-C typing could explain the significant number of positive cytotoxic T lymphocyte precursor frequency (CTLpf) tests found among HLA-AB-subtype, DRB1/B3/B5-subtype matched patient/donor pairs, we have identified by sequencing the incompatibilities recognized by CD8+ CTL clones obtained from such positive CTLpf tests. In most cases the target molecules were HLA-C antigens that had escaped detection by serology (e.g. Cw*1601, 1502 or 0702). Direct recognition of HLA-C by a CTL clone was demonstrated by lysis of the HLA class I-negative 721.221 cell line transfected with Cw*1601 cDNA. Because of the functional importance of Cw polymorphism, a PCR-SSO oligotyping procedure was set up allowing the resolution of 29 Cw alleles. Oligotyping of a panel of 382 individuals (including 101 patients and their 272 potential unrelated donors, 5 related donors and 4 platelet donors) allowed to determine HLA-C and HLA A-B-Cw-DRB1 allelic frequencies, as well as a number of A-Cw, B-Cw, and DRB1-Cw associations. Two new HLA-Cw alleles (Cw*02023 and Cw*0707) were identified by DNA sequencing of PCR-amplified exon 2-intron 2-exon 3 amplicons. Furthermore, we determined the degree of HLA-C compatibility in 287 matched pairs that could be formed from 73 patients and their 184 potential unrelated donors compatible for HLA-AB by serology and for HLA-DRB1/ B3/B5 by oligotyping. Cw mismatches were identified in 42.1% of these pairs, and AB-subtype oligotyping showed that 30% of these Cw-incompatible pairs were also mismatched for A or B-locus subtype. The degree of HLA-C incompatibility was strongly influenced by the linkage with B alleles and by the ABDR haplotypes. Cw alleles linked with B*4403, B*5101, B18, and B62 haplotypes were frequently mismatched. Apparently high resolution DNA typing for HLA-AB does not result in full matching at locus C. Since HLA-C polymorphism is recognized by alloreactive CTLs, such incompatibilities might be as relevant as AB-subtype mismatches in clinical transplantation.

Extensive gene traffic on the mammalian X chromosome.

Mammalian sex chromosomes have undergone profound changes since evolving from ancestral autosomes. By examining retroposed genes in the human and mouse genomes, we demonstrate that, during evolution, the mammalian X chromosome has generated and recruited a disproportionately high number of functional retroposed genes, whereas the autosomes experienced lower gene turnover. Most autosomal copies originating from X-linked genes exhibited testis-biased expression. Such export is incompatible with mutational bias and is likely driven by natural selection to attain male germline function. However, the excess recruitment is consistent with a combination of both natural selection and mutational bias.

A link between FXYD3 (Mat-8)-mediated Na,K-ATPase regulation and differentiation of Caco-2 intestinal epithelial cells.

FXYD3 (Mat-8) proteins are regulators of Na,K-ATPase. In normal tissue, FXYD3 is mainly expressed in stomach and colon, but it is also overexpressed in cancer cells, suggesting a role in tumorogenesis. We show that FXYD3 silencing has no effect on cell proliferation but promotes cell apoptosis and prevents cell differentiation of human colon adenocarcinoma cells (Caco-2), which is reflected by a reduction in alkaline phosphatase and villin expression, a change in several other differentiation markers, and a decrease in transepithelial resistance. Inhibition of cell differentiation in FXYD3-deficient cells is accompanied by an increase in the apparent Na+ and K+ affinities of Na,K-ATPase, reflecting the absence of Na,K-pump regulation by FXYD3. In addition, we observe a decrease in the maximal Na,K-ATPase activity due to a decrease in its turnover number, which correlates with a change in Na,K-ATPase isozyme expression that is characteristic of cancer cells. Overall, our results suggest an important role of FXYD3 in cell differentiation of Caco-2 cells. One possibility is that FXYD3 silencing prevents proper regulation of Na,K-ATPase, which leads to perturbation of cellular Na+ and K+ homeostasis and changes in the expression of Na,K-ATPase isozymes, whose functional properties are incompatible with Caco-2 cell differentiation.

Inhibition of lymphocyte mediated cytotoxicity by perforin antisense oligonucleotides.

The granule/perforin exocytosis model of CTL mediated cytolysis proposes that CTL, upon recognition of the specific targets, release the cytolytic, pore-forming protein perforin into the intercellular space which then mediates the cytotoxic effect. However, direct evidence for the involvement of perforin is still lacking, and indeed, recent results even seem incompatible with the model. To determine directly the role of perforin in CTL cytotoxicity, perforin antisense oligonucleotides were exogenously added during the stimulation of mouse spleen derived T cells and human peripheral blood lymphocytes (PBL), respectively. Perforin protein expression in lymphocytes was reduced by up to 65%, and cytotoxicity of stimulated T cells by as much as 69% (5.7-fold). These results provide the first experimental evidence for a crucial role of perforin in lymphocyte mediated cytotoxicity.

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Cette contribution a pour objectif d'analyser dans quelle mesure la mise en oeuvre de la politique publique d'éducation (en Suisse) est compatible - ou incompatible - avec la politique conjoncturelle . Elle vise à mettre en évidence le lien - ou l'absence de lien - entre les réformes implémentées depuis les années 1970 dans le système éducatif et l'évolution conjoncturelle. En d'autres termes, elle cherche à déterminer si la mise en oeuvre des réformes éducationnelles a pu avoir une influence pro ou anti-cyclique sur la conjoncture.

Speciation in the Sorex araneus (Mammalia, Insectivora)

The seven cytologically known species of the Sorex araneus complex each show a different karyotype. The three European species are genetically and morphologically very close, and mostly allopatric, thus having similar ecological requirements. It is suggested that chromosomic changes occasion a stasipatric speciation, the formation of chromosomic races in S. araneus being an illustration of this process. Neither small demes nor high inbreeding are likely in Sorex; thus the Robertsonian changes should spread out by meiotic drive alone, and the hybrids for a change should be almost fully fertile. Chromosomic speciation occurs when two incompatible metacentrics meet together. This model explains the separation between S. araneus and S. coronatus, but geographical isolation must have occured in the case of S. granarius, which keeps a primitive karyotype.

Ligand-dependent inhibition of CD1d-restricted NKT cell development in mice transgenic for the activating receptor Ly49D.

In addition to their CD1d-restricted T cell receptor (TCR), natural killer T (NKT) cells express various receptors normally associated with NK cells thought to act, in part, as modulators of TCR signaling. Immunoreceptor-tyrosine activation (ITAM) and inhibition (ITIM) motifs associated with NK receptors may augment or attenuate perceived TCR signals respectively, potentially influencing NKT cell development and function. ITIM-containing Ly49 family receptors expressed by NKT cells are proposed to play a role in their development and function. We have produced mice transgenic for the ITAM-associated Ly49D and ITIM-containing Ly49A receptors and their common ligand H2-Dd to determine the importance of these signaling interplays in NKT cell development. Ly49D/H2-Dd transgenic mice had selectively and severely reduced numbers of thymic and peripheral NKT cells, whereas both ligand and Ly49D transgenics had normal numbers of NKT cells. CD1d tetramer staining revealed a blockade of NKT cell development at an early precursor stage. Coexpression of a Ly49A transgene partially rescued NKT cell development in Ly49D/H2-Dd transgenics, presumably due to attenuation of ITAM signaling. Thus, Ly49D-induced ITAM signaling is incompatible with the early development of cells expressing semi-invariant CD1d-restricted TCRs and appropriately harmonized ITIM-ITAM signaling is likely to play an important role in the developmental program of NKT cells.

Concomitant administration of intravenous drugs in the ICU: evaluation of physico-chemical compatibilities

Background and objective: Patients in the ICU often get many intravenous (iv) drugs at the same time. Even with three-lumen central venous catheters, the administration of more than one drug in the same iv line (IVL) is frequently necessary. The objective of this study was to observe how nurses managed to administer these many medications and to evaluate the proportion of two-drugs associations (TDA) that are compatible or not, based on known compatibility data. Design: Observational prospective study over 4 consecutive months. All patients receiving simultaneously more than one drugs in the same IVL (Y-site injection or mixed in the same container) were included. For each patient, all iv drugs were recorded, as well as concentration, infusion solution, location on the IVL system, time, rate and duration of administration. For each association of two or more drugs, compatibility of each drug was checked with each other. Compatibilities between these pairs of drugs were assessed using published data (mainly Trissel LA. Handbook on Injectable Drugs and Trissel's Tables of Physical Compatibility) and visual tests performed in our quality control laboratory. Setting: 34 beds university hospital adult ICU. Main outcome measures: Percentage of compatibilities and incompatibilities between drugs administered in the same IVL. Results: We observed 1,913 associations of drugs administered together in the same IVL, 783 implying only two drugs. The average number of drugs per IVL was 3.1 ± 0.8 (range: 2-9). 83.2% of the drugs were given by continuous infusion, 14.3% by intermittent infusion and 2.5% in bolus. The associations observed allowed to form 8,421 pairs of drugs (71.7% drug-drug and 28.3% drug-solute). According to literature data, 80.2% of the association were considered as compatible and 4.4% incompatible. 15.4% were not interpretable because of different conditions between local practices and those described in the literature (drug concentration, solute, etc.) or because of a lack of data. After laboratory tests performed on the most used drugs (furosemide, KH2PO4, morphine HCl, etc.), the proportion of compatible TDA raised to 85.7%, the incompatible stayed at 4.6% and only 9.7% remain unknown or not interpretable. Conclusions: Nurses managed the administration of iv medications quite well, as only less than 5% of observed TDA were considered as incompatible. But the 10% of TDA with unavailable compatibility data should have been avoided too, since the consequences of their concomitant administration cannot be predictable. For practical reasons, drugs were analysed only by pairs, which constitutes the main limit of this work. The average number of drugs in the same association being three, laboratory tests are currently performed to evaluate some of the most observed three-drugs associations.

Insight in protein S deficiency from mouse models

Protein S (ProS) is an important negative regulator of blood coagulation. Its physiological importance is evident in purpura fulminans and other life-threatening thrombotic disorders typical of ProS deficient patients. Our previous characterization of ProS deficiency in mouse models has shown similarities with the human phenotypes: heterozygous ProS-deficient mice (Pros+/-) had increased thrombotic risk whereas homozygous deficiency in ProS (Pros-/-) was incompatible with life (Blood 2009; 114:2307-2314). In tissues, ProS exerts cellular functions by binding to and activating tyrosine kinase receptors of the Tyro3 family (TAM) on the cell surface.To extend the analysis of coagulation defects beyond the Pros-/- phenotype and add new insights into the sites of synthesis ProS and its action, we generated mice with inactivated ProS in hepatocytes (Proslox/loxAlbCre+) as well as in endothelial and hematopoietic cells (Proslox/loxTie2Cre+). Both models resulted in significant reduction of circulating ProS levels and in a remarkable increased thrombotic risk in vivo. In a model of tissue factor (TF)-induced venous thromboembolism (VTE), only 17% of Proslox/loxAlbCre+ mice (n=12) and only 13% of Proslox/loxTie2Cre+ mice (n=14) survived, compared with 86% of Proslox/lox mice (n=14; P<0.001).To mimic a severe acquired ProS deficiency, ProS gene was inactivated at the adult stage using the polyI:C-inducible Mx1-Cre system (Proslox/loxMx1Cre+). Ten days after polyI:C treatment, Proslox/loxMx1Cre+ mice developed disseminated intravascular coagulation with extensive lung and liver thrombosis.It is worth noting that no skin lesions compatible with purpura fulminans were observed in any of the above-described models of partial ProS deficiency. In order to shed light on the pathogenesis of purpura fulminans, we exposed the different ProS-deficient mice to warfarin (0.2 mg/day). We observed that Pros+/-, Proslox/loxAlbCre+ and Proslox/loxTie2Cre+ mice developed retiform purpura (characterized by erythematous and necrotic lesions of the genital region and extremities) and died after 3 to 5 days after the first warfarin administration.In human, ProS is also synthesized by megakaryocytes and hence stored at high concentrations in circulating platelets (pProS). The role of pProS has been investigated by generating megakaryocyte ProS-deficient model using the PF4 promoter as Cre driver (Proslox/loxPf4Cre+). In the TF-induced VTE model, Proslox/loxPf4Cre+ (n=15) mice showed a significant increased risk of thrombosis compared to Proslox/lox controls (n=14; survival rate 47% and 86%, respectively; P<0.05). Furthermore, preliminary results suggest survival to be associated with higher circulating ProS levels. In order to evaluate the potential role of pProS in thrombus formation, we investigated the thrombotic response to intravenous injection of collagen-epinephrine in vivo and platelet function in vitro. Both in vivo and in vitro experiments showed similar results between Proslox/loxPf4Cre+ and Proslox/lox, indicating that platelet reactivity was not influenced by the absence of pProS. These data suggest that pProS is delivered at the site of thrombosis to inhibit thrombin generation.We further investigated the ability of ProS to function as a ligand of TAM receptors, by using homozygous and heterozygous deficient mice for both the TAM ligands ProS and Gas6. Gas6-/-Pros-/- mice died in utero and showed comparable dramatic bleeding and thrombotic phenotype as described for Pros-/- embryos.In conclusion, like complete ProS deficiency, double deficiency in ProS and Gas6 was lethal, whereas partial ProS deficiency was not. Mice partially deficient in ProS displayed a prothrombotic phenotype, including those with only deficiency in pProS. Purpura fulminans did not occur spontaneously in mice with partial Pros deficiency but developed upon warfarin administration.Thus, the use of different mice models of ProS deficiency can be instrumental in the study of its highly variable thrombotic phenotype and in the investigation of additional roles of ProS in inflammation and autoimmunity through TAM signaling.

What uses are mating types? The "developmental switch" model.

Why mating types exist at all is subject to much debate. Among hypotheses, mating types evolved to control organelle transmission during sexual reproduction, or to prevent inbreeding or same-clone mating. Here I review data from a diversity of taxa (including ciliates, algae, slime molds, ascomycetes, and basidiomycetes) to show that the structure and function of mating types run counter the above hypotheses. I argue instead for a key role in triggering developmental switches. Genomes must fulfill a diversity of alternative programs along the sexual cycle. As a haploid gametophyte, an individual may grow vegetatively (through haploid mitoses), or initiate gametogenesis and mating. As a diploid sporophyte, similarly, it may grow vegetatively (through diploid mitoses) or initiate meiosis and sporulation. Only diploid sporophytes (and not haploid gametophytes) should switch on the meiotic program. Similarly, only haploid gametophytes (not sporophytes) should switch on gametogenesis and mating. And they should only do so when other gametophytes are ready to do the same in the neighborhood. As argued here, mating types have evolved primarily to switch on the right program at the right moment.

Trace element partitioning in HP-LT metamorphic assemblages during subduction-related metamorphism, Ile de Groix, France: a detailed LA-ICPMS study

Devolatilization reactions and subsequent transfer of fluid from subducted oceanic crust into the overlying mantle wedge are important processes, which are responsible for the specific geochemical characteristics of subduction-related metamorphic rocks, as well as those of arc magmatism. To better understand the geochemical fingerprint induced by fluid mobilization during dehydration and rehydration processes related to subduction zone metamorphism, the trace element and rare earth element (REE) distribution patterns in HP-LT metamorphic assemblages in eclogite-, blueschist- and greenschist-facies rocks of the Ile de Groix were obtained by laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) analysis. This study focuses on 10 massive basic rocks representing former hydrothermally altered mid-ocean ridge basalts (MORB), four banded basic rocks of volcano-sedimentary origin and one micaschist. The main hosts for incompatible trace elements are epidote (REE, Th, U, Pb, Sr), garnet [Y, heavy REE (HREE)], phengite (Cs, Rb, Ba, B), titanite [Ti, Nb, Ta, REE; HREE > LREE (light REE)], rutile (Ti, Nb, Ta) and apatite (REE, Sr). The trace element contents of omphacite, amphibole, albite and chlorite are low. The incompatible trace element contents of minerals are controlled by the stable metamorphic mineral assemblage and directly related to the appearance, disappearance and reappearance of minerals, especially epidote, garnet, titanite, rutile and phengite, during subduction zone metamorphism. Epidote is a key mineral in the trace element exchange process because of its large stability field, ranging from lower greenschist- to blueschist- and eclogite-facies conditions. Different generations of epidote are generally observed and related to the coexisting phases at different stages of the metamorphic cycle (e.g. lawsonite, garnet, titanite). Epidote thus controls most of the REE budget during the changing P-T conditions along the prograde and retrograde path. Phengite also plays an important role in determining the large ion lithophile element (LILE) budget, as it is stable to high P-T conditions. The breakdown of phengite causes the release of LILE during retrogression. A comparison of trace element abundances in whole-rocks and minerals shows that the HP-LT metamorphic rocks largely retain the geochemical characteristics of their basic, volcano-sedimentary and pelitic protoliths, including a hydrothermal alteration overprint before the subduction process. A large part of the incompatible trace elements remained trapped in the rocks and was recycled within the various metamorphic assemblages stable under changing metamorphic conditions during the subduction process, indicating that devolatilization reactions in massive basic rocks do not necessarily imply significant simultaneous trace element and REE release.

Melt variability in percolated peridotite: an experimental study applied to reactive migration of tholeiitic basalt in the upper mantle

Melt-rock reaction in the upper mantle is recorded in a variety of ultramafic rocks and is an important process in modifying melt composition on its way from the source region towards the surface. This experimental study evaluates the compositional variability of tholeiitic basalts upon reaction with depleted peridotite at uppermost-mantle conditions. Infiltration-reaction processes are simulated by employing a three-layered set-up: primitive basaltic powder ('melt layer') is overlain by a 'peridotite layer' and a layer of vitreous carbon spheres ('melt trap'). Melt from the melt layer is forced to move through the peridotite layer into the melt trap. Experiments were conducted at 0.65 and 0.8 GPa in the temperature range 1,170-1,290 degrees C. In this P-T range, representing conditions encountered in the transition zone (thermal boundary layer) between the asthenosphere and the lithosphere underneath oceanic spreading centres, the melt is subjected to fractionation, and the peridotite is partially melting (T (s) similar to 1,260 degrees C). The effect of reaction between melt and peridotite on the melt composition was investigated across each experimental charge. Quenched melts in the peridotite layers display larger compositional variations than melt layer glasses. A difference between glasses in the melt and peridotite layer becomes more important at decreasing temperature through a combination of enrichment in incompatible elements in the melt layer and less efficient diffusive equilibration in the melt phase. At 1,290A degrees C, preferential dissolution of pyroxenes enriches the melt in silica and dilutes it in incompatible elements. Moreover, liquids become increasingly enriched in Cr(2)O(3) at higher temperatures due to the dissolution of spinel. Silica contents of liquids decrease at 1,260 degrees C, whereas incompatible elements start to concentrate in the melt due to increasing levels of crystallization. At the lowest temperatures investigated, increasing alkali contents cause silica to increase as a consequence of reactive fractionation. Pervasive percolation of tholeiitic basalt through an upper-mantle thermal boundary layer can thus impose a high-Si 'low-pressure' signature on MORB. This could explain opx + plag enrichment in shallow plagioclase peridotites and prolonged formation of olivine gabbros.

Geochemical study of vertebrate fossils from the Upper Cretaceous (Santonian) Csehbanya Formation (Hungary): Evidence for a freshwater habitat of mosasaurs and pycnodont fish

The diverse vertebrate remains from the Upper Cretaceous freshwater settings at Iharkut, Hungary, contain two fossil groups, Pycnodontiformes fish and Mosasauridae that are almost exclusively known from marine palaeo-environments. Hence, their appearance in alluvial sediments is very unusual. Trace element and isotope compositions of the remains have been analyzed to investigate the taphonomy and the ecological differences among the different fossil groups present at Iharkut. All examined fossils have undergone post-depositional diagenetic alteration, which resulted in high concentrations of REE, U, and Fe, together with almost complete homogenization of delta(18)O(CO3) values. Similar REE patterns in different fossils suggest a common origin for all remains, hence the discovered species most likely lived in the same local ecosystem. Despite partial diagenetic overprinting, the delta(18)O(PO4) values of the fossils indicate sufficient taxon-specific isotopic diversity to permit some broad conclusions on the palaeo-environment of the fossils. In particular, it is apparent that the isotopic composition of the Pycnodontiformes fish and Mosasauridae remains is most compatible with a freshwater palaeo-habitat and incompatible with a marine palaeo-environment. In addition, the Sr concentration and isotope data indicate that the Pycnodontiformes and Mosasauridae likely lived predominantly in a freshwater environment and were not simply occasional visitors to the Iharkut river ecosystem. Regarding other fossil groups, high delta(18)O(PO4) values of Alligatoroidea and Iharkutosuchus teeth suggest that these small crocodile species might have inhabited swamps and ponds where the water was relatively rich in (18)O due to evaporation. (c) 2009 Elsevier B.V. All rights reserved.

Effects of season, sex and body size on the feeding ecology of turtle-headed seasnakes (Emydocephalus annulatus) on IndoPacific inshore coral reefs

In terrestrial snakes, many cases of intraspecific shifts in dietary habits as a function of predator sex and body size are driven by gape-limitation - and hence, are most common in species that feed on relatively large prey, and exhibit a wide body-size range. Our data on seasnakes reveal an alternative mechanism for intraspecific niche partitioning, based on sex-specific seasonal anorexia induced by reproductive activities. Turtle-headed seasnakes (Emydocephalus annulatus) on coral reefs in the New Caledonian Lagoon feed entirely on the eggs of demersal-spawning fishes. DNA sequence data (cytochrome b gene) on eggs that we palpated from stomachs of 37 snakes showed that despite this ontogenetic-stage specialization, the prey come from a taxonomically diverse array of species including damselfish (41% of samples, at least 5 species), blennies (41%, 4 species) and gobies (19%, 5 species). The composition of snake diets shifted seasonally (with damselfish dominating in winter but not summer), presumably reflecting seasonality of fish reproduction. That seasonal shift affects male and female snakes differently, because reproduction is incompatible with foraging. Adult female seasnakes ceased feeding when they became heavily distended with developing embryos in late summer, and males ceased feeding while they were mate-searching in winter. The sex divergence in foraging habits may be amplified by sexual size dimorphism; females grow larger than males, and larger snakes (of both sexes) feed more on damselfish (which often lay their eggs in exposed sites) than on blennies and gobies (whose eggs are hidden within narrow crevices). Specific features of reproductive biology of coral-reef fish (seasonality and nest type) have generated intraspecific niche partitioning in these seasnakes, by mechanisms different from those that apply to terrestrial snakes.