Multiplicity one for LL-functions and applications

We give conditions for when two Euler products are the same given that they satisfy a functional equation and their coefficients satisfy a partial Ramanujan bound and do not differ by too much. Additionally, we prove a number of multiplicity one type results for the number-theoretic objects attached to $L$-functions. These results follow from our main result about $L$-functions

Characterizations of the Saito-Kurokawa lifting: a survey

There are a variety of characterizations of Saito-Kurokawa lifts from elliptic modular forms to Siegel modular forms of degree 2. In addition to giving a survey of known characterizations, we apply a recent result of Weissauer to provide a number of new and simpler characterizations of Saito-Kurokawa lifts

Dynamics of confined water reconstructed from inelastic x-ray scattering measurements of bulk response functions

Nanoconfined water and surface-structured water impacts a broad range of fields. For water confined between hydrophilic surfaces, measurements and simulations have shown conflicting results ranging from “liquidlike” to “solidlike” behavior, from bulklike water viscosity to viscosity orders of magnitude higher. Here, we investigate how a homogeneous fluid behaves under nanoconfinement using its bulk response function: The Green's function of water extracted from a library of S(q,ω) inelastic x-ray scattering data is used to make femtosecond movies of nanoconfined water. Between two confining surfaces, the structure undergoes drastic changes as a function of surface separation. For surface separations of ≈9 Å, although the surface-associated hydration layers are highly deformed, they are separated by a layer of bulklike water. For separations of ≈6 Å, the two surface-associated hydration layers are forced to reconstruct into a single layer that modulates between localized “frozen’ and delocalized “melted” structures due to interference of density fields. These results potentially reconcile recent conflicting experiments. Importantly, we find a different delocalized wetting regime for nanoconfined water between surfaces with high spatial frequency charge densities, where water is organized into delocalized hydration layers instead of localized hydration shells, and are strongly resistant to `freezing' down to molecular distances (<6 Å)

Axillary surgery in women with sentinel node-positive operable breast cancer: a systematic review with meta-analyses

Traditionally, women with node-positive operable breast cancer have received complete axillary lymph node dissection (ALND), which is associated with significant morbidity, but recently less invasive alternatives have been explored. We conducted a systematic review of randomised controlled trials assessing alternative approaches to axillary surgery in patients with pathologically-confirmed sentinel node-positive operable breast cancer. We searched on 16/3/15 the Specialized Register of the Cochrane Breast Cancer group; CENTRAL; MEDLINE; PreMEDLINE; EMBASE; WHO International Clinical Trials Registry Portal; ClinicalTrials.gov; conference proceedings from ASCO and the San Antonio Breast Cancer meetings; checked reference lists and contacted authors to identify relevant studies. Double, independent study sifting, extraction, appraisal and summarising were undertaken using standard Cochrane Collaboration methodology. We included three studies (2020 patients) comparing ALND with sentinel lymph node dissection (SLND) to SLND alone, and two studies (1899 patients) comparing ALND to axillary radiotherapy (aRT). No differences in survival or recurrence were observed between ALND and SLND or aRT, but morbidity may have been increased in ALND, and all the results were subject to different biases, such as recruitment bias, performance bias, and outcome-reporting bias. Whilst it is encouraging that there appears to be no adverse effect on recurrence or survival, it will be appropriate to confirm these findings and provide additional data confirming quality of life effects and long term outcomes

Two interdependent mechanisms of antimicrobial activity allow for efficient killing in nylon-3-based polymeric mimics of innate immunity peptides

AbstractNovel synthetic mimics of antimicrobial peptides have been developed to exhibit structural properties and antimicrobial activity similar to those of natural antimicrobial peptides (AMPs) of the innate immune system. These molecules have a number of potential advantages over conventional antibiotics, including reduced bacterial resistance, cost-effective preparation, and customizable designs. In this study, we investigate a family of nylon-3 polymer-based antimicrobials. By combining vesicle dye leakage, bacterial permeation, and bactericidal assays with small-angle X-ray scattering (SAXS), we find that these polymers are capable of two interdependent mechanisms of action: permeation of bacterial membranes and binding to intracellular targets such as DNA, with the latter necessarily dependent on the former. We systemically examine polymer-induced membrane deformation modes across a range of lipid compositions that mimic both bacteria and mammalian cell membranes. The results show that the polymers' ability to generate negative Gaussian curvature (NGC), a topological requirement for membrane permeation and cellular entry, in model Escherichia coli membranes correlates with their ability to permeate membranes without complete membrane disruption and kill E. coli cells. Our findings suggest that these polymers operate with a concentration-dependent mechanism of action: at low concentrations permeation and DNA binding occur without membrane disruption, while at high concentrations complete disruption of the membrane occurs. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova

Self-assembling dipeptide antibacterial nanostructures with membrane disrupting activity.

Peptide-based supramolecular assemblies are a promising class of nanomaterials with important biomedical applications, specifically in drug delivery and tissue regeneration. However, the intrinsic antibacterial capabilities of these assemblies have been largely overlooked. The recent identification of common characteristics shared by antibacterial and self-assembling peptides provides a paradigm shift towards development of antibacterial agents. Here we present the antibacterial activity of self-assembled diphenylalanine, which emerges as the minimal model for antibacterial supramolecular polymers. The diphenylalanine nano-assemblies completely inhibit bacterial growth, trigger upregulation of stress-response regulons, induce substantial disruption to bacterial morphology, and cause membrane permeation and depolarization. We demonstrate the specificity of these membrane interactions and the development of antibacterial materials by integration of the peptide assemblies into tissue scaffolds. This study provides important insights into the significance of the interplay between self-assembly and antimicrobial activity and establishes innovative design principles toward the development of antimicrobial agents and materials

Functional Characteristics of the Gut Microbiome in C57BL/6 Mice Differentially Susceptible to Plasmodium yoelii

C57BL/6 mice are widely used for in vivo studies of immune function and metabolism in mammals. In a previous study, it was observed that when C57BL/6 mice purchased from different vendors were infected with Plasmodium yoelii, a causative agent of murine malaria, they exhibited both differential immune responses and significantly different parasite burdens: these patterns were reproducible when gut contents were transplanted into gnotobiotic mice. To gain insight into the mechanism of resistance, we removed whole ceca from mice purchased from two vendors, Taconic Biosciences (low parasitemia) and Charles River Laboratories (high parasitemia), to determine the combined host and microflora metabolome and metatranscriptome. With the exception of two Charles River samples, we observed 90% similarity in overall bacterial gene expression within vendors and 80% similarity between vendors. In total 33 bacterial genes were differentially expressed in Charles River mice (p-value \u3c 0.05) relative to the mice purchased from Taconic. Included among these, fliC, ureABC, and six members of the nuo gene family were overrepresented in microbiomes susceptible to more severe malaria. Moreover, 38 mouse genes were differentially expressed in these purported genetically identical mice. Differentially expressed genes included basigin, a cell surface receptor required for P. falciparum invasion of red blood cells. Differences in metabolite pools were detected, though their relevance to malaria infection, microbial community activity, or host response is not yet understood. Our data have provided new targets that may connect gut microbial activity to malaria resistance and susceptibility phenotypes in the C57BL/6 model organism