Extraction of timelike entanglement from the quantum vacuum

An intriguing property of the massless quantum vacuum state is that it contains entanglement between both spacelike and timelike separated regions of space-time. The implications of timelike entanglement and its connection to standard entanglement, however, are unexplored. Here we show that timelike entanglement can be extracted from the massless Minkowski vacuum and converted into standard entanglement "at a given time" between two inertial, two-state detectors at the same spatial location: one coupled to the field in the past and the other coupled to the field in the future. The procedure used here demonstrates a time correlation as a requirement for extraction; e. g., if the past detector was active at a quarter to 12:00, then the future detector must wait to become active at precisely a quarter past 12:00 in order to achieve entanglement

Autologous hematopoietic stem cell transplantation for mantle cell lymphoma

AbstractThis study evaluated the outcomes of patients who underwent high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (autoHSCT) for mantle cell non-Hodgkin's lymphoma and the effect of clinical and treatment characteristics. The clinical outcome and prognostic factors in 40 patients who underwent HDC and autoHSCT for mantle cell lymphoma between June 1991 and August 1998 were analyzed. With a median follow-up of 24 months for the surviving patients (range, 4-68 months), the 2-year overall survival was 65% and the 2-year event-free survival (EFS) was 36%. In univariate analysis, characteristics predictive of a poor EFS were blastic morphology (P = .019) and the patient having received 3 or more prior chemotherapy regimens (P = .004). In a multivariate analysis, the only factor associated with a poor EFS was the number of prior chemotherapy regimens. Those patients who received 3 or more prior therapies had a 2-year EFS of 0%, and those who received <3 therapies had a 2-year EFS of 45% (P = .004). Patients with mantle cell lymphoma can obtain prolonged EFS with HDC and autoHSCT; however, this strategy for prolonged EFS appears to work optimally in patients who are less heavily pretreated. Whether this therapy will increase the overall survival or EFS in patients receiving transplants in first complete remission will need to be tested in prospective randomized clinical trials.Biol Blood Marrow Transplant 2000;6(6):640-5

Kinetic and structural analysis of a bacterial protein tyrosine phosphatase-like myo-inositol polyphosphatase. Protein Sci

Abstract PhyA from Selenomonas ruminantium (PhyAsr), is a bacterial protein tyrosine phosphatase (PTP)-like inositol polyphosphate phosphatase (IPPase) that is distantly related to known PTPs. PhyAsr has a second substrate binding site referred to as a standby site and the P-loop (HCX 5 R) has been observed in both open (inactive) and closed (active) conformations. Site-directed mutagenesis and kinetic and structural studies indicate PhyAsr follows a classical PTP mechanism of hydrolysis and has a broad specificity toward polyphosphorylated myo-inositol substrates, including phosphoinositides. Kinetic and molecular docking experiments demonstrate PhyAsr preferentially cleaves the 3-phosphate position of Ins P 6 and will produce Ins(2)P via a highly ordered series of sequential dephosphorylations: D-Ins(1,2,4,5,6)P 5 , Ins(2,4,5,6)P 4 , D-Ins(2,4,5)P 3 , and D-Ins(2,4)P 2 . The data support a distributive enzyme mechanism and suggest the PhyAsr standby site is involved in the recruitment of substrate. Structural studies at physiological pH and high salt concentrations demonstrate the &apos;&apos;closed&apos;&apos; or active P-loop conformation can be induced in the absence of substrate. These results suggest PhyAsr should be reclassified as a D-3 myo-inositol hexakisphosphate phosphohydrolase and suggest the PhyAsr reaction mechanism is more similar to that of PTPs than previously suspected. Keywords: inositol polyphosphate phosphatase; protein tyrosine phosphatase; phosphoinositide phosphatase; phytase; myo-inositol; P-loop; hydrolysis pathway Supplemental material: see www.proteinscience.org Protein tyrosine phosphatase (PTP) superfamily enzymes have been discovered in a range of prokaryotes, and most appear to serve roles that mimic their better-known eukaryotic counterparts as regulators of cellular function The X-ray crystallographic structure of PhyAsr Article published online ahead of print. Article and publication date are at http://www.proteinscience.org/cg

Genome-wide miRNAprofiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis

miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1–positive MCL (n = 30) and cyclin D1–negative MCL (n =7) and compared them with small lymphocytic leukemia/ lymphoma (n =12), aggressive B-cell lymphomas (n =138), normal B-cell subsets, and stromal cells.We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNAclassifier showed consistent results in formalinfixed paraffin-embedded tissues and was able to distinguish cyclin D1–negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from small lymphocytic leukemia/lymphoma, dominated by 23 up-regulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL patients demonstrated a cluster characterized by high expression of miRNAs from the polycistronic miR17-92 cluster and its paralogs, miR-106a-363 and miR-106b-25, and associated with high proliferation gene signature. The other clusters showed enrichment of stroma-associated miRNAs, and also had higher expression of stroma-associated genes. Our clinical outcome analysis in the present study suggested that miRNAs can serve as prognosticators

Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse lymphomagenesis

DNA methyltransferase 3B (Dnmt3b) belongs to a family of enzymes responsible for methylation of cytosine residues in mammals. DNA methylation contributes to the epigenetic control of gene transcription and is deregulated in virtually all human tumors. To better understand the generation of cancer-specific methylation patterns, we genetically inactivated Dnmt3b in a mouse model of MYC-induced lymphomagenesis. Ablation of Dnmt3b function using a conditional knockout in T cells accelerated lymphomagenesis by increasing cellular proliferation, which suggests that Dnmt3b functions as a tumor suppressor. Global methylation profiling revealed numerous gene promoters as potential targets of Dnmt3b activity, the majority of which were demethylated in Dnmt3b–/– lymphomas, but not in Dnmt3b–/– pretumor thymocytes, implicating Dnmt3b in maintenance of cytosine methylation in cancer. Functional analysis identified the gene Gm128 (which we termed herein methylated in normal thymocytes [Ment]) as a target of Dnmt3b activity. We found that Ment was gradually demethylated and overexpressed during tumor progression in Dnmt3b–/– lymphomas. Similarly, MENT was overexpressed in 67% of human lymphomas, and its transcription inversely correlated with methylation and levels of DNMT3B. Importantly, knockdown of Ment inhibited growth of mouse and human cells, whereas overexpression of Ment provided Dnmt3b+/+ cells with a proliferative advantage. Our findings identify Ment as an enhancer of lymphomagenesis that contributes to the tumor suppressor function of Dnmt3b and suggest it could be a potential target for anticancer therapies

One-dimension cubic-quintic Gross-Pitaevskii equation in Bose-Einstein condensates in a trap potential

By means of new general variational method we report a direct solution for the quintic self-focusing nonlinearity and cubic-quintic 1D Gross Pitaeskii equation (GPE) in a harmonic confined potential. We explore the influence of the 3D transversal motion generating a quintic nonlinear term on the ideal 1D pure cigar-like shape model for the attractive and repulsive atom-atom interaction in Bose Einstein condensates (BEC). Also, we offer a closed analytical expression for the evaluation of the error produced when solely the cubic nonlinear GPE is considered for the description of 1D BEC.Comment: 6 pages, 3 figure

Molecular Diagnosis of Primary Mediastinal B Cell Lymphoma Identifies a Clinically Favorable Subgroup of Diffuse Large B Cell Lymphoma Related to Hodgkin Lymphoma

Using current diagnostic criteria, primary mediastinal B cell lymphoma (PMBL) cannot be distinguished from other types of diffuse large B cell lymphoma (DLBCL) reliably. We used gene expression profiling to develop a more precise molecular diagnosis of PMBL. PMBL patients were considerably younger than other DLBCL patients, and their lymphomas frequently involved other thoracic structures but not extrathoracic sites typical of other DLBCLs. PMBL patients had a relatively favorable clinical outcome, with a 5-yr survival rate of 64% compared with 46% for other DLBCL patients. Gene expression profiling strongly supported a relationship between PMBL and Hodgkin lymphoma: over one third of the genes that were more highly expressed in PMBL than in other DLBCLs were also characteristically expressed in Hodgkin lymphoma cells. PDL2, which encodes a regulator of T cell activation, was the gene that best discriminated PMBL from other DLBCLs and was also highly expressed in Hodgkin lymphoma cells. The genomic loci for PDL2 and several neighboring genes were amplified in over half of the PMBLs and in Hodgkin lymphoma cell lines. The molecular diagnosis of PMBL should significantly aid in the development of therapies tailored to this clinically and pathogenetically distinctive subgroup of DLBCL

Molecular diagnosis of Burkitt\u27s lymphoma.

BACKGROUND: The distinction between Burkitt\u27s lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt\u27s lymphoma from diffuse large-B-cell lymphoma. METHODS: Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation. RESULTS: A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt\u27s lymphoma. Burkitt\u27s lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target genes, the expression of a subgroup of germinal-center B-cell genes, and the low level of expression of major-histocompatibility-complex class I genes and nuclear factor-kappaB target genes. Eight specimens with a pathological diagnosis of diffuse large-B-cell lymphoma had the typical gene-expression profile of Burkitt\u27s lymphoma, suggesting they represent cases of Burkitt\u27s lymphoma that are difficult to diagnose by current methods. Among 28 of the patients with a molecular diagnosis of Burkitt\u27s lymphoma, the overall survival was superior among those who had received intensive chemotherapy regimens instead of lower-dose regimens. CONCLUSIONS: Gene-expression profiling is an accurate, quantitative method for distinguishing Burkitt\u27s lymphoma from diffuse large-B-cell lymphoma

Taxation and market power

"We analyze the incidence and welfare effects of unit sales taxes in experimental monopoly and Bertrand markets. We find, in line with economic theory, that firms with no market power are able to shift a high share of a tax burden on to consumers, independent of whether buyers are automated or human players. In monopoly markets, a monopolist bears a large share of the burden of a tax increase. With human buyers, however, this share is smaller than with automated buyers as the presence of human buyers constrains the pricing behavior of a monopolist." (author's abstract)"Dieser Artikel untersucht Inzidenz- und Wohlfahrtseffekte einer Mengensteuer in experimentellen Monopol- und Bertrand-Märkten. Im Einklang mit der ökonomischen Theorie sind Firmen ohne Marktmacht in der Lage, einen großen Anteil der Last einer Steuererhöhung an die Konsumenten weiterzugeben. Dies gilt unabhängig davon, ob die Käufer simuliert sind oder die Kaufentscheidungen durch reale Käufer getroffen werden. In Monopolmärkten trägt der Monopolist einen großen Anteil der Last einer Steuererhöhung. Werden die Kaufentscheidungen durch reale Käufer getroffen, ist dieser Anteil jedoch kleiner als mit simulierten Käufern, da reale Käufer im Experiment das Preissetzungsverhalten des Monopolisten einschränken." (Autorenreferat