A Gelfand triple approach to Wigner and Husimi representations

The notion of Gelfand triples is applied to interpret mathematically a family of phase-space representations of quantum mechanics interpolating between the Wigner and Husimi representations. Gelfand triples of operators on Hilbert space, and Gelfand triples of functions on phase-space are introduced in order to get isomorphic correspondences between operators and their phase-space representations. The phasespace Gelfand triples are characterized by means of growth conditions on the analytic continuation of the functions. We give integral expressions for the sesquilinear forms belonging to the phase-space Gelfand triples. This provides mathematically rigorous phase-space analogues for quantum mechanical expectation values of bounded operators. 1

Intradermal Administration of Influenza Vaccine with Trehalose and Pullulan-Based Dissolving Microneedle Arrays

Most influenza vaccines are administered via intramuscular injection which has several disadvantages that might jeopardize the compliance of vaccinees. Intradermal administration of dissolving-microneedle-arrays (dMNAs) could serve as minimal invasive alternative to needle injections. However, during the production process of dMNAs antigens are subjected to several stresses, which may reduce their potency. Moreover, the needles need to have sufficient mechanical strength to penetrate the skin and subsequently dissolve effectively to release the incorporated antigen. Here, we investigated whether blends of trehalose and pullulan are suitable for the production of stable dMNA fulfilling these criteria. Our results demonstrate that production of trehalose/pullulan-based dMNAs rendered microneedles that were sharp and stiff enough to pierce into ex vivo human skin and subsequently dissolve within 15 min. The mechanical properties of the dMNAs were maintained well even after four weeks of storage at temperatures up to 37°C. In addition, immunization of mice with influenza antigens via both freshly prepared dMNAs and dMNAs after storage (four weeks at 4°C or 37°C) resulted in antibody titers of similar magnitude as found in intramuscularly injected mice and partially protected mice from influenza virus infection. Altogether, our results demonstrate the potential of trehalose/pullulan-based dMNAs as alternative dosage form for influenza vaccination.Drug Delivery Technolog

Toll-like receptor 2-modulating pectin-polymers in alginate-based microcapsules attenuate immune responses and support islet-xenograft survival

Encapsulation of pancreatic islets in alginate-microcapsules is used to reduce or avoid the application of life-long immunosuppression in preventing rejection. Long-term graft function, however, is limited due to varying degrees of host tissue responses against the capsules. Major graft-longevity limiting responses include inflammatory responses provoked by biomaterials and islet-derived danger-associated molecular patterns (DAMPs). This paper reports on a novel strategy for engineering alginate microcapsules presenting immunomodulatory polymer pectin with varying degrees of methyl-esterification (DM) to reduce these host tissue responses. DM18-pectin/alginate microcapsules show a significant decrease of DAMP-induced Toll-Like Receptor-2 mediated immune activation in vitro, and reduce peri-capsular fibrosis in vivo in mice compared to higher DM-pectin/alginate microcapsules and conventional alginate microcapsules. By testing efficacy of DM18-pectin/alginate microcapsules in vivo, we demonstrate that low-DM pectin support long-term survival of xenotransplanted rat islets in diabetic mice. This study provides a novel strategy to attenuate host responses by creating immunomodulatory capsule surfaces that attenuate activation of specific pro-inflammatory immune receptors locally at the transplantation site

The level and distribution of methyl-esters influence the impact of pectin on intestinal T cells, microbiota, and Ahr activation

Pectins are dietary fibres that modulate T cell immunity, microbiota composition, and fermentation profiles, but how this is influenced by the degree of methyl-esterification (DM) and degree-of-blockiness (DB) of pectin is unknown. Here, we demonstrate that supplementation of DM19(high-DB), DM49(low-DB) and DM43(high-DB) pectins at a low dose increased the frequencies of intestinal T-helper (Th)1 and Th2 cells after 1 week of pectin supplementation in mice, whereas DM18(low-DB) did not. After 4 weeks of supplementation with those pectins, Th1 and Th2 frequencies returned to control levels, whereas Rorγt+ regulatory T-cell frequencies increased. These structure-dependent effects could derive from induced shifts in microbiota composition that differed between DM18(low-DB) pectin and the other pectins. T-cell-modulating effects were not short-chain-fatty acid-dependent, but rather through an increase in Aryl-hydrocarbon-receptor-activating components. Thus, pectins with a specific combination of DM and DB have an impact on intestinal T cell-immunity in mice, when supplemented at a low dose

Response to comment on 'Amphibian fungal panzootic causes catastrophic and ongoing loss of biodiversity'

Lambert et al. question our retrospective and holistic epidemiological assessment of the role of chytridiomycosis in amphibian declines. Their alternative assessment is narrow and provides an incomplete evaluation of evidence. Adopting this approach limits understanding of infectious disease impacts and hampers conservation efforts. We reaffirm that our study provides unambiguous evidence that chytridiomycosis has affected at least 501 amphibian species

Short-Course Radiotherapy Followed by Neoadjuvant Bevacizumab, Capecitabine, and Oxaliplatin and Subsequent Radical Treatment in Primary Stage IV Rectal Cancer:Long-Term Results of a Phase II Study

Background. In a Dutch phase II trial conducted between 2006 and 2010, short-course radiotherapy followed by systemic therapy with capecitabine, oxaliplatin, and bevacizumab as neoadjuvant treatment and subsequent radical surgical treatment of primary tumor and metastatic sites was evaluated. In this study, we report the long-term results after a minimum follow-up of 6 years. Methods. Patients with histologically confirmed rectal adenocarcinoma with potentially resectable or ablatable metastases in liver or lungs were eligible. Follow-up data were collected for all patients enrolled in the trial. Overall and recurrence-free survival were calculated using the Kaplan-Meier method. Results. Follow-up data were available for all 50 patients. After a median follow-up time of 8.1 years (range 6.0-9.8), 16 patients (32.0%) were still alive and 14 (28%) were disease-free. The median overall survival was 3.8 years (range 0.5-9.4). From the 36 patients who received radical treatment, two (5.6%) had a local recurrence and 29 (80.6%) had a distant recurrence. Conclusions. Long-term survival can be achieved in patients with primary metastatic rectal cancer after neoadjuvant radio- and chemotherapy. Despite a high number of recurrences, 32% of patients were alive after a median follow-up time of 8.1 years

Limited Value of Staging Squamous Cell Carcinoma of the Anal Margin and Canal Using the Sentinel Lymph Node Procedure: A Prospective Study with Long-Term Follow-Up

Background. Selection of patients with anal cancer for groin irradiation is based on tumor size, palpation, ultrasound, and fine needle cytology. Current staging of anal cancer may result in undertreatment in small tumors and overtreatment of large tumors. This study reports the feasibility of the sentinel lymph node biopsy (SLNB) in patients with anal cancer and whether this improves the selection for inguinal radiotherapy. Methods. A total of 50 patients with squamous anal cancer were evaluated prospectively. Patients without a SLNB (n = 29) received irradiation of the inguinal lymph nodes based on lymph node status, tumor size, and location of the primary tumor. Inguinal irradiation treatment in patients with a SLNB was based on the presence of metastases in the SLN. Results. SLNs were found in all 21 patients who underwent a SLNB. There were 5 patients (24%) who had complications after SLNB and 7 patients (33%) who had a positive SLN and received inguinal irradiation. However, 2 patients with a tumor-free SLN and no inguinal irradiation developed lymph node metastases after 12 and 24 months, respectively. Conclusions. We conclude that SLNB in anal cancer is technically feasible. SLNB can identify those patients who would benefit from refrain of inguinal irradiation treatment and thereby reducing the incidence of unnecessary inguinal radiotherapy. However, because of the occurrence of inguinal lymph node metastases after a tumor-negative SLNB, introduction of this procedure as standard of care in all patients with anal carcinoma should be done with caution to avoid undertreatment of patient who otherwise would benefit from inguinal radiotherapy

Distribution of the Iberian Calopteryx Damselflies and Its Relation with Bioclimatic Belts: Evolutionary and Biogeographic Implications

Using bioclimatic belts as habitat and distribution predictors, the present study examines the implications of the potential distributions of the three Iberian damselflies, Calopteryx Leach (Odonata: Calopterygidae), with the aim of investigating the possible consequences in specific interactions among the species from a sexual selection perspective and of discussing biogeographical patterns. To obtain the known distributions, the literature on this genus was reviewed, relating the resulting distributions to bioclimatic belts. Specific patterns related to bioclimatic belts were clearly observed in the Mediterranean region. The potential distribution maps and relative frequencies might involve latitudinal differences in relative abundances, C. virgo meridionalis Sélys being the most abundant species in the Eurosiberian region, C. xanthostoma (Charpentier) in the northern half of the Mediterranean region and C. haemorrhoidalis (Vander Linden) in the rest of this region. These differences might explain some previously described latitudinal differences in secondary sexual traits in the three species. Changes in relative abundances may modulate interactions among these species in terms of sexual selection and may produce sexual character displacement in this genus. C. virgo meridionalis distribution and ecological requirements explain its paleobiogeography as a species which took refuge in Iberia during the Würm glaciation. Finally, possible consequences in species distributions and interactions are discussed within a global climate change context