A Feynman integral in Lifshitz-point and Lorentz-violating theories in R^D ⨁ R<i>^m</i>

We evaluate a 1-loop, 2-point, massless Feynman integral ID,m(p,q) relevant for perturbative field theoretic calculations in strongly anisotropic d=D+m dimensional spaces given by the direct sum RD ⨁ Rm . Our results are valid in the whole convergence region of the integral for generic (noninteger) codimensions D and m. We obtain series expansions of ID,m(p,q) in terms of powers of the variable X:=4p2/q4, where p=|p|, q=|q|, p Є RD, q Є Rm, and in terms of generalised hypergeometric functions 3F2(−X), when X&lt;1. These are subsequently analytically continued to the complementary region X≥1. The asymptotic expansion in inverse powers of X1/2 is derived. The correctness of the results is supported by agreement with previously known special cases and extensive numerical calculations

Simulating `Complex' Problems with Quantum Monte Carlo

We present a new quantum Monte Carlo algorithm suitable for generically complex problems, such as systems coupled to external magnetic fields or anyons in two spatial dimensions. We find that the choice of gauge plays a nontrivial role, and can be used to reduce statistical noise in the simulation. Furthermore, it is found that noise can be greatly reduced by approximate cancellations between the phases of the (gauge dependent) statistical flux and the external magnetic flux.Comment: Revtex, 11 pages. 3 postscript files for figures attache

The a-theorem and conformal symmetry breaking in holographic RG flows

We study holographic models describing an RG flow between two fixed points driven by a relevant scalar operator. We show how to introduce a spurion field to restore Weyl invariance and compute the anomalous contribution to the generating functional in even dimensional theories. We find that the coefficient of the anomalous term is proportional to the difference of the conformal anomalies of the UV and IR fixed points, as expected from anomaly matching arguments in field theory. For any even dimensions the coefficient is positive as implied by the holographic a-theorem. For flows corresponding to spontaneous breaking of conformal invariance, we also compute the two-point functions of the energy-momentum tensor and the scalar operator and identify the dilaton mode. Surprisingly we find that in the simplest models with just one scalar field there is no dilaton pole in the two-point function of the scalar operator but a stronger singularity. We discuss the possible implications.Comment: 50 pages. v2: minor changes, added references, extended discussion. v3: we have clarified some of the calculations and assumptions, results unchanged. v4: published version in JHE

Maturation-Induced Cloaking of Neutralization Epitopes on HIV-1 Particles

To become infectious, HIV-1 particles undergo a maturation process involving proteolytic cleavage of the Gag and Gag-Pol polyproteins. Immature particles contain a highly stable spherical Gag lattice and are impaired for fusion with target cells. The fusion impairment is relieved by truncation of the gp41 cytoplasmic tail (CT), indicating that an interaction between the immature viral core and gp41 within the particle represses HIV-1 fusion by an unknown mechanism. We hypothesized that the conformation of Env on the viral surface is regulated allosterically by interactions with the HIV-1 core during particle maturation. To test this, we quantified the binding of a panel of monoclonal antibodies to mature and immature HIV-1 particles by immunofluorescence imaging. Surprisingly, immature particles exhibited markedly enhanced binding of several gp41-specific antibodies, including two that recognize the membrane proximal external region (MPER) and neutralize diverse HIV-1 strains. Several of the differences in epitope exposure on mature and immature particles were abolished by truncation of the gp41 CT, thus linking the immature HIV-1 fusion defect with altered Env conformation. Our results suggest that perturbation of fusion-dependent Env conformational changes contributes to the impaired fusion of immature particles. Masking of neutralization-sensitive epitopes during particle maturation may contribute to HIV-1 immune evasion and has practical implications for vaccine strategies targeting the gp41 MPER

Primary fallopian tube carcinoma: review of MR imaging findings

Objectives To review the epidemiological and clinical features of primary fallopian tube carcinoma (PFTC), and to illustrate the spectrum of MRI findings, with pathological confirmation. Methods This article reviews the relevant literature on the epidemiological, clinical, and imaging features of primary fallopian tube carcinoma, with pathological confirmation, using illustrations from the authors' teaching files. Results Primary fallopian tube carcinoma came under focus over the last few years due to its possible role on the pathogenesis of high-grade serous epithelial ovarian and peritoneal cancers. Typical symptoms, together with the presence of some of the most characteristic MRI signs, such as a "sausage-shaped" pelvic mass, hydrosalpinx, and hydrometra, may signal the presence of primary fallopian cancer, and allow the radiologist to report it as a differential diagnosis. Conclusions Primary fallopian tube carcinoma has a constellation of clinical symptoms and magnetic resonance imaging features, which may be diagnostic. Although these findings are not present together in the majority of cases, radiologists who are aware of them may include the diagnosis of primary fallopian tube cancer in their report more frequently and with more confidence. Teaching Points PFTC may be more frequent than previously thought PFTC has specific clinical and MRI characteristics Knowledge of typical PFTC signs enables its inclusion in the differential diagnosis PFTC is currently staged under the 2013 FIGO system PFTC is staged collectively with ovarian and peritoneal neoplasmsinfo:eu-repo/remantics/publishedVersio

Flip-Flop of Phospholipids in Proteoliposomes Reconstituted from Detergent Extract of Chloroplast Membranes: Kinetics and Phospholipid Specificity

Eukaryotic cells are compartmentalized into distinct sub-cellular organelles by lipid bilayers, which are known to be involved in numerous cellular processes. The wide repertoire of lipids, synthesized in the biogenic membranes like the endoplasmic reticulum and bacterial cytoplasmic membranes are initially localized in the cytosolic leaflet and some of these lipids have to be translocated to the exoplasmic leaflet for membrane biogenesis and uniform growth. It is known that phospholipid (PL) translocation in biogenic membranes is mediated by specific membrane proteins which occur in a rapid, bi-directional fashion without metabolic energy requirement and with no specificity to PL head group. A recent study reported the existence of biogenic membrane flippases in plants and that the mechanism of plant membrane biogenesis was similar to that found in animals. In this study, we demonstrate for the first time ATP independent and ATP dependent flippase activity in chloroplast membranes of plants. For this, we generated proteoliposomes from Triton X-100 extract of intact chloroplast, envelope membrane and thylakoid isolated from spinach leaves and assayed for flippase activity using fluorescent labeled phospholipids. Half-life time of flipping was found to be 6±1 min. We also show that: (a) intact chloroplast and envelope membrane reconstituted proteoliposomes can flip fluorescent labeled analogs of phosphatidylcholine in ATP independent manner, (b) envelope membrane and thylakoid reconstituted proteoliposomes can flip phosphatidylglycerol in ATP dependent manner, (c) Biogenic membrane ATP independent PC flipping activity is protein mediated and (d) the kinetics of PC translocation gets affected differently upon treatment with protease and protein modifying reagents

The Bacterial Defensin Resistance Protein MprF Consists of Separable Domains for Lipid Lysinylation and Antimicrobial Peptide Repulsion

Many bacterial pathogens achieve resistance to defensin-like cationic antimicrobial peptides (CAMPs) by the multiple peptide resistance factor (MprF) protein. MprF plays a crucial role in Staphylococcus aureus virulence and it is involved in resistance to the CAMP-like antibiotic daptomycin. MprF is a large membrane protein that modifies the anionic phospholipid phosphatidylglycerol with l-lysine, thereby diminishing the bacterial affinity for CAMPs. Its widespread occurrence recommends MprF as a target for novel antimicrobials, although the mode of action of MprF has remained incompletely understood. We demonstrate that the hydrophilic C-terminal domain and six of the fourteen proposed trans-membrane segments of MprF are sufficient for full-level lysyl-phosphatidylglycerol (Lys-PG) production and that several conserved amino acid positions in MprF are indispensable for Lys-PG production. Notably, Lys-PG production did not lead to efficient CAMP resistance and most of the Lys-PG remained in the inner leaflet of the cytoplasmic membrane when the large N-terminal hydrophobic domain of MprF was absent, indicating a crucial role of this protein part. The N-terminal domain alone did not confer CAMP resistance or repulsion of the cationic test protein cytochrome c. However, when the N-terminal domain was coexpressed with the Lys-PG synthase domain either in one protein or as two separate proteins, full-level CAMP resistance was achieved. Moreover, only coexpression of the two domains led to efficient Lys-PG translocation to the outer leaflet of the membrane and to full-level cytochrome c repulsion, indicating that the N-terminal domain facilitates the flipping of Lys-PG. Thus, MprF represents a new class of lipid-biosynthetic enzymes with two separable functional domains that synthesize Lys-PG and facilitate Lys-PG translocation. Our study unravels crucial details on the molecular basis of an important bacterial immune evasion mechanism and it may help to employ MprF as a target for new anti-virulence drugs

Genome-Wide Association between Branch Point Properties and Alternative Splicing

The branch point (BP) is one of the three obligatory signals required for pre-mRNA splicing. In mammals, the degeneracy of the motif combined with the lack of a large set of experimentally verified BPs complicates the task of modeling it in silico, and therefore of predicting the location of natural BPs. Consequently, BPs have been disregarded in a considerable fraction of the genome-wide studies on the regulation of splicing in mammals. We present a new computational approach for mammalian BP prediction. Using sequence conservation and positional bias we obtained a set of motifs with good agreement with U2 snRNA binding stability. Using a Support Vector Machine algorithm, we created a model complemented with polypyrimidine tract features, which considerably improves the prediction accuracy over previously published methods. Applying our algorithm to human introns, we show that BP position is highly dependent on the presence of AG dinucleotides in the 3′ end of introns, with distance to the 3′ splice site and BP strength strongly correlating with alternative splicing. Furthermore, experimental BP mapping for five exons preceded by long AG-dinucleotide exclusion zones revealed that, for a given intron, more than one BP can be chosen throughout the course of splicing. Finally, the comparison between exons of different evolutionary ages and pseudo exons suggests a key role of the BP in the pathway of exon creation in human. Our computational and experimental analyses suggest that BP recognition is more flexible than previously assumed, and it appears highly dependent on the presence of downstream polypyrimidine tracts. The reported association between BP features and the splicing outcome suggests that this, so far disregarded but yet crucial, element buries information that can complement current acceptor site models