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We develop a general framework to assess capabilities and limitations of the Gaussian toolbox in continuous variable quantum information theory. Our framework allows us to characterize the structure and properties of quantum resource theories specialized to Gaussian states and Gaussian operations, establishing rigorous methods for their description and yielding a unified approach to their quantification. We show in particular that, under a few intuitive and physically motivated assumptions on the set of free states, no Gaussian quantum resource can be distilled with free Gaussian operations, even when an unlimited supply of the resource state is available. This places fundamental constraints on state manipulations in all such Gaussian resource theories. We discuss in particular the applications to quantum entanglement, where we extend previously known results by showing that Gaussian entanglement cannot be distilled even with Gaussian operations preserving the positivity of the partial transpose, as well as to other Gaussian resources such as steering and optical nonclassicality. A comprehensive semidefinite programming representation of all these resources is explicitly provided. *

We investigate the ultimate precision achievable in Gaussian quantum metrology. We derive general analytical expressions for the quantum Fisher information matrix and for the measurement compatibility condition, ensuring asymptotic saturability of the quantum Cramér-Rao bound, for the estimation of multiple parameters encoded in multimode Gaussian states. We then apply our results to the joint estimation of a phase shift and two parameters characterizing Gaussian phase covariant noise in optical interferometry. In such a scheme, we show that two-mode displaced squeezed input probes with optimally tuned squeezing and displacement fulfil the measurement compatibility condition and enable the simultaneous estimation of all three parameters, with an advantage over individual estimation schemes that quickly rises with increasing mean energy of the probes.

The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) shuttles between the cytoplasm and nucleus and plays important roles in RNA metabolism. Whereas nuclear hnRNP A1 has been shown to bind intronic sequences and modulate splicing, cytoplasmic hnRNP A1 is associated with poly(A) ؉ RNA, indicating different RNA ligand specificity. Previous studies indicated that cytoplasmic hnRNP A1 is capable of high-affinity binding of reiterated AUUUA sequences (ARE) that have been shown to modulate mRNA turnover and translation. Through a combination of two-dimensional gel and proteolysis studies, we establish hnRNP A1 (or structurally related proteins that are post-translationally regulated in an identical manner) as the dominant cytoplasmic protein in human T lymphocytes capable of interacting with the ARE contained within the context of full-length granulocyte-macrophage colony-stimulating factor mRNA. We additionally demonstrate that cytoplasmic hnRNP A1 preferentially binds ARE relative to pre-mRNAs in both cross-linking and mobility shift experiments. RNA polymerase II inhibition increased the binding of ARE (AUBP activity) and poly(U)-Sepharose by cytoplasmic hnRNP A1, while nuclear hnRNP A1 binding was unaffected. Nuclear and cytoplasmic hnRNP A1 could be distinguished by the differential sensitivity of their RNA binding to diamide and N-ethylmaleimide. The increase in AUBP activity of cytoplasmic hnRNP A1 following RNA polymerase II inhibition correlated with serine-threonine dephosphorylation, as determined by inhibitor and metabolic labeling studies. Thus, cytoplasmic and nuclear hnRNP A1 exhibit different RNA binding profiles, perhaps transduced through serine-threonine phosphorylation. These findings are relevant to the specific ability of hnRNP A1 to serve distinct roles in post-transcriptional regulation of gene expression in both the nucleus and cytoplasm.The heterogeneous nuclear ribonucleoproteins (hnRNP) 1 were originally defined as the proteins constituting the 40 S complexes isolated from nuclei following nuclease treatment (reviewed in Refs. 1 and 2). The hnRNP proteins range in mass from 30 to 120 kDa and associate with pre-mRNA as a complex (1, 2). Studies of hnRNP-RNA interactions have demonstrated sequence-specific binding, both in vitro and in vivo (3-5), as well as roles in pre-mRNA splicing and splice-site selection (2, 6, 7). Consistent with this latter observation, native hnRNP A1 and C proteins have been reported to bind a polypyrimidine stretch bordered by AG at the 3Ј end of introns (7,8). Similar findings have been made with recombinant hnRNP A1 (9, 10), which demonstrated equivalent binding to 5Ј-and 3Ј-intronic splice sites (9). These findings are of functional interest because hnRNP A1 has been shown to modulate the effects of splicing factor 2 (SF2/ASF), and promote distal 5Ј-splice site selection (8,(11)(12)(13).The role of hnRNP A1 in mRNA metabolism expanded with demonstration that hnRNP A1 shuttles between the nucleus and the cytoplasm (14). With inhibition of RNA polymerase II t...

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Glycogenosis type II is a recessively inherited disorder caused by mutations in the acid maltase (GAA) gene. Clinically, three different phenotypes are recognized: Infantile, juvenile and adult forms. A majority of compound heterozygous adult-onset patients carry a t-13g mutation in intron 1 associated with splicing out the first coding exon (exon 2). We have studied the mechanism of this mutation in a model system with wild-type and mutant minigenes expressed in a GAA deficient cell line. We have demonstrated that the mutation does not prevent normal splicing; low levels of correctly spliced mRNA are generated with the mutant construct. The data explain why the mutation is restricted to a milder, adult-onset phenotype. We also demonstrate that splicing out of exon 2 occurs with the wild-type construct, and thus represents alternative splicing which takes place in normal cells. Three splice variants (SV1, SV2 and SV3) are made with both the mutant and the wild-type constructs. Furthermore, as shown by RNAse protection assay, these mRNA variants are less abundant with the mutant construct. Thus, a major effect of the mutation appears to be a low splicing efficiency, since the total amount of all the transcripts generated from the mutant construct is reduced compared with the wild type. The removal of approximately 90% of the intron 1 (2.6 kb) sequence resulted in a dramatic increase in the levels of correctly spliced mRNA, indicating that the intron may contain a powerful transcriptional repressor.

The macrophage is critical to the innate immune response and contributes to human diseases, including inflammatory arthritis and plaque formation in atherosclerosis. Vascular endothelial growth factor (VEGF) is an angiogenic cytokine that is produced by macrophages. To study the regulation of VEGF production in macrophages we show that stimulation of monocyte‐macrophage‐like RAW‐264.7 cells by lipopolysaccharide (LPS) increases expression of VEGF mRNA and protein. Three alternative splicing VEGF mRNA isoforms are produced, and the stability of VEGF mRNA increases following cellular activation. To study post‐transcriptional regulation of the VEGF gene the 3′‐untranslated region (3′ UTR) was introduced into the 3′ UTR of the luciferase gene in a reporter construct. In both RAW‐264.7 cells and thioglycollate‐elicited macrophages, the 3′ UTR sequence dramatically reduces reporter expression. Treatment with activators of macrophages, including LPS, lipoteichoic acid, and VEGF protein, stimulates expression of 3′ UTR reporters. Finally, mapping studies of the 3′ UTR of VEGF mRNA show that deletion of the heterogeneous nuclear ribonucleoprotein l binding site affects basal reporter expression in RAW‐264.7 cells, but does not affect reporter activation with LPS. Together these results demonstrate that a post‐transcriptional mechanism contributes to VEGF gene expression in activated macrophage cells.

We introduce a genetic algorithm that designs quantum optics experiments for engineering quantum states with specific properties. Our algorithm is powerful and flexible, and can easily be modified to find methods of engineering states for a range of applications. Here we focus on quantum metrology. First, we consider the noise-free case, and use the algorithm to find quantum states with a large quantum Fisher information (QFI). We find methods, which only involve experimental elements that are available with current or near-future technology, for engineering quantum states with up to a 100-fold improvement over the best classical state, and a 20-fold improvement over the optimal Gaussian state. Such states are a superposition of the vacuum with a large number of photons (around 80), and can hence be seen as Schrödinger-cat-like states. We then apply the two most dominant noise sources in our setting -photon loss and imperfect heralding -and use the algorithm to find quantum states that still improve over the optimal Gaussian state with realistic levels of noise. This will open up experimental and technological work in using exotic non-Gaussian states for quantum-enhanced phase measurements. Finally, we use the Bayesian mean square error to look beyond the regime of validity of the QFI, finding quantum states with precision enhancements over the alternatives even when the experiment operates in the regime of limited data.PACS numbers: