Deflagrations in hybrid CONe white dwarfs: a route to explain the faint Type Iax supernova 2008ha

Stellar evolution models predict the existence of hybrid white dwarfs (WDs) with a carbon-oxygen core surrounded by an oxygen-neon mantle. Being born with masses ~1.1 Msun, hybrid WDs in a binary system may easily approach the Chandrasekhar mass (MCh) by accretion and give rise to a thermonuclear explosion. Here, we investigate an off-centre deflagration in a near-MCh hybrid WD under the assumption that nuclear burning only occurs in carbon-rich material. Performing hydrodynamics simulations of the explosion and detailed nucleosynthesis post-processing calculations, we find that only 0.014 Msun of material is ejected while the remainder of the mass stays bound. The ejecta consist predominantly of iron-group elements, O, C, Si and S. We also calculate synthetic observables for our model and find reasonable agreement with the faint Type Iax SN 2008ha. This shows for the first time that deflagrations in near-MCh WDs can in principle explain the observed diversity of Type Iax supernovae. Leaving behind a near-MCh bound remnant opens the possibility for recurrent explosions or a subsequent accretion-induced collapse in faint Type Iax SNe, if further accretion episodes occur. From binary population synthesis calculations, we find the rate of hybrid WDs approaching MCh to be on the order of 1 percent of the Galactic SN Ia rate.Comment: 9 pages, 7 figures, 2 tables, accepted for publication in MNRA

Kidney autotransplantation after nephrectomy and work bench surgery as an ultimate approach to nephron-sparing surgery

Kidney autotransplantation (KAT) is the ultimate approach for nephron-sparing surgery. It is a rarely used method in renal tumor surgery today as minimal invasive and open techniques for nephron-sparing surgery improve constantly. In this publication, the complication rate and the long-term functional and oncological outcome at a single center are analyzed.Methods A prospectively constructed database of patients with renal tumors who underwent renal surgery was retrospectively analyzed to identify patients with KAT and describe surgical and oncological outcomes and to obtain long-term follow-up. Data collection included detailed surgical technique, complications (Clavian-Dindo), and hospital stay, as well as functional and oncological outcome and long-term follow-up.Results Between 1976 and 2013, 12 patients (median age 50.5 years) underwent KAT for highly complex renal masses: in five cases for complex renal cell carcinoma (RCC), five cases for complex upper urinary tract carcinoma (UTUC), one case for a renal metastasis, and one case for nephroblastoma. The nephrectomy or nephron-ureterectomy was performed open via a flank or transabdominal. The median surgical time was 360 min (range 270–490 min). Intraoperatively, six cases required blood transfusions (50%). Six patients (50%) developed significant postoperative complications (Clavian-Dindo > 2). In two patients, intermittent hemodialysis for delayed graft function (16.6%) was needed, and in six cases (50%), additional blood transfusions postoperatively were necessary. At discharge from hospital, all patients had functioning grafts. The median hospital stay was 29.5 days (range 18–35). At follow-up (median follow-up of 83.5 ± 40.7 months), six patients had died (50%)—all with functioning grafts (free from hemodialysis). In five cases, recurrence of primary tumor or metastatic disease was recorded. In four cases, the recurrent carcinoma could be resected; in detail, UTUC in three cases and one partial nephrectomy of the autotransplanted kidney was performed. One patient suffered from bone and lung metastasis. Two patients died finally tumor-related. Five patients (41.6%) are presently alive, without evidence of tumor relapse. One patient developed terminal renal failure requiring hemodialysis 105 months after autotransplantation. One additional patient was lost to follow-up; after 69 months, this patient had a functioning kidney and no evidence of disease-recurrence at the last follow-up. A cumulative number of 1424 months without hemodialysis was gained for these 12 patients. In the literature to date, most KAT are performed in benign disease, with minor but frequent complication. Here, we report the largest series of KAT for malignant kidney tumors. The complication rates are similar, compared to the recently reported series for benign indications with an improved graft survival rate. Since KAT requires a complex and challenging surgical approach, it should be performed by experienced kidney transplant surgeons.Conclusion In very complex cases involving renal tumors and multi-morbidity, patients should be counseled well before KAT is considered. At the same time, KAT should not be abandoned in these very rare cases, especially when a nephron-sparing approach is otherwise not feasible. KAT can maintain renal function and quality of life and extend expectancy of life

Dynamic Orienteering on a Network of Queues

Abstract We propose a stochastic orienteering problem on a network of queues with time windows at customers. While this problem is of wide applicability, we study it in the context of routing and scheduling a textbook salesperson who visits professors on campus to gain textbook adoptions. The salesperson must determine which professors to visit and how long to wait in queues at each professor. We model the problem as a Markov decision process (MDP) with the objective of maximizing expected sales. We investigate the existence of optimal control limits and examine conditions under which certain actions cannot be optimal. To solve the problem, we propose an approximate dynamic programming approach based on rollout algorithms. The method introduces a two-stage heuristic estimation that we refer to as compound rollout. In the first stage, the algorithm decides whether to stay at the current professor or go to another professor. If departing the current professor, it chooses the professor to whom to go in the second stage. We demonstrate the value of our modeling and solution approaches by comparing the dynamic policies to a-priori-route solutions with recourse actions

The P2Y12 receptor induces platelet aggregation through weak activation of the αIIbβ3 integrin – a phosphoinositide 3-kinase-dependent mechanism

AbstractHigh concentrations of adenosine-5′-diphosphate ADP are able to induce partial aggregation without shape change of P2Y1 receptor-deficient mouse platelets through activation of the P2Y12 receptor. In the present work we studied the transduction pathways selectively involved in this phenomenon. Flow cytometric analyses using R-phycoerythrin-conjugated JON/A antibody (JON/A-PE), an antibody which recognizes activated mouse αIIbβ3 integrin, revealed a low level activation of αIIbβ3 in P2Y1 receptor-deficient platelets in response to 100 μM ADP or 1 μM 2MeS-ADP. Adrenaline induced no such activation but strongly potentiated the effect of ADP in a dose-dependent manner. Global phosphorylation of 32P-labeled platelets showed that P2Y12-mediated aggregation was not accompanied by an increase in the phosphorylation of myosin light chain (P20) or pleckstrin (P47) and was not affected by the protein kinase C (PKC) inhibitor staurosporine. On the other hand, two unrelated phosphoinositide 3-kinase inhibitors, wortmannin and LY294002, inhibited this aggregation. Our results indicate that (i) the P2Y12 receptor is able to trigger a P2Y1 receptor-independent inside-out signal leading to αIIbβ3 integrin activation and platelet aggregation, (ii) ADP and adrenaline use different signaling pathways which synergize to activate the αIIbβ3 integrin, and (iii) the transduction pathway triggered by the P2Y12 receptor is independent of PKC but dependent on phosphoinositide 3-kinase

Distribution of Gold Nanoparticles in the Anterior Chamber of the Eye after Intracameral Injection for Glaucoma Therapy

In glaucoma therapy, nanoparticles (NPs) are a favorable tool for delivering drugs to the outflow tissues of the anterior chamber of the eye where disease development and progression take place. In this context, a prerequisite is an efficient enrichment of NPs in the trabecular meshwork with minimal accumulation in off-target tissues such as the cornea, lens, iris and ciliary body. We evaluated the optimal size for targeting the trabecular meshwork by using gold NPs of 5, 60, 80 and 120 nm with a bare surface (AuNPs) or coated with hyaluronic acid (HA-AuNPs). NPs were compared regarding their colloidal stability, distribution in the anterior chamber of the eye ex vivo and cellular uptake in vitro. HA-AuNPs demonstrated an exceptional colloidal stability. Even after application into porcine eyes ex vivo, the HA coating prevented an aggregation of NPs inside the trabecular meshwork. NPs with a diameter of 120 nm exhibited the highest volume-based accumulation in the trabecular meshwork. Off-target tissues in the anterior chamber demonstrated an exceptionally low gold content. Our findings are particularly important for NPs with encapsulated anti-glaucoma drugs because a higher particle volume would be accompanied by a higher drug payload

Navigating the integration of biotic interactions in biogeography

Biotic interactions are widely recognised as the backbone of ecological communities, but how best to study them is a subject of intense debate, especially at macro-ecological scales. While some researchers claim that biotic interactions need to be observed directly, others use proxies and statistical approaches to infer them. Despite this ambiguity, studying and predicting the influence of biotic interactions on biogeographic patterns is a thriving area of research with crucial implications for conservation. Three distinct approaches are currently being explored. The first approach involves empirical observation and measurement of biotic interactions' effects on species demography in laboratory or field settings. While these findings contribute to theory and to understanding species' demographies, they can be challenging to generalise on a larger scale. The second approach centers on inferring biotic associations from observed co-occurrences in space and time. The goal is to distinguish the environmental and biotic effects on species distributions. The third approach constructs extensive potential interaction networks, known as metanetworks, by leveraging existing knowledge about species ecology and interactions. This approach analyses local realisations of these networks using occurrence data and allows understanding large distributions of multi-taxa assemblages. In this piece, we appraise these three approaches, highlighting their respective strengths and limitations. Instead of seeing them as conflicting, we advocate for their integration to enhance our understanding and expand applications in the emerging field of interaction biogeography. This integration shows promise for ecosystem understanding and management in the Anthropocene era

Combustion in thermonuclear supernova explosions

Type Ia supernovae are associated with thermonuclear explosions of white dwarf stars. Combustion processes convert material in nuclear reactions and release the energy required to explode the stars. At the same time, they produce the radioactive species that power radiation and give rise to the formation of the observables. Therefore, the physical mechanism of the combustion processes, as reviewed here, is the key to understand these astrophysical events. Theory establishes two distinct modes of propagation for combustion fronts: subsonic deflagrations and supersonic detonations. Both are assumed to play an important role in thermonuclear supernovae. The physical nature and theoretical models of deflagrations and detonations are discussed together with numerical implementations. A particular challenge arises due to the wide range of spatial scales involved in these phenomena. Neither the combustion waves nor their interaction with fluid flow and instabilities can be directly resolved in simulations. Substantial modeling effort is required to consistently capture such effects and the corresponding techniques are discussed in detail. They form the basis of modern multidimensional hydrodynamical simulations of thermonuclear supernova explosions. The problem of deflagration-to-detonation transitions in thermonuclear supernova explosions is briefly mentioned.Comment: Author version of chapter for 'Handbook of Supernovae,' edited by A. Alsabti and P. Murdin, Springer. 24 pages, 4 figure

Fasudil Loaded PLGA Microspheres as Potential Intravitreal Depot Formulation for Glaucoma Therapy

Rho-associated protein kinase (ROCK) inhibitors allow for causative glaucoma therapy. Unfortunately, topically applied ROCK inhibitors suffer from high incidence of hyperemia and low intraocular bioavailability. Therefore, we propose the use of poly (lactide-co-glycolide) (PLGA) microspheres as a depot formulation for intravitreal injection to supply outflow tissues with the ROCK inhibitor fasudil over a prolonged time. Fasudil-loaded microspheres were prepared by double emulsion solvent evaporation technique. The chemical integrity of released fasudil was confirmed by mass spectrometry. The biological activity was measured in cell-based assays using trabecular meshwork cells (TM cells), Schlemm's canal cells (SC cells), fibroblasts and adult retinal pigment epithelium cells (ARPE-19). Cellular response to fasudil after its diffusion through vitreous humor was investigated by electric cell-substrate impedance sensing. Microspheres ranged in size from 3 to 67 mu m. The release of fasudil from microspheres was controllable and sustained for up to 45 days. Released fasudil reduced actin stress fibers in TM cells, SC cells and fibroblasts. Decreased collagen gel contraction provoked by fasudil was detected in TM cells (similar to 2.4-fold), SC cells (similar to 1.4-fold) and fibroblasts (similar to 1.3-fold). In addition, fasudil readily diffused through vitreous humor reaching its target compartment and eliciting effects on TM cells. No negative effects on ARPE-19 cells were observed. Since fasudil readily diffuses through the vitreous humor, we suggest that an intravitreal drug depot of ROCK inhibitors could significantly improve current glaucoma therapy particularly for patients with comorbid retinal diseases

Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

Peer reviewedPublisher PD

In-situ characterization of the Hamamatsu R5912-HQE photomultiplier tubes used in the DEAP-3600 experiment

The Hamamatsu R5912-HQE photomultiplier-tube (PMT) is a novel high-quantum efficiency PMT. It is currently used in the DEAP-3600 dark matter detector and is of significant interest for future dark matter and neutrino experiments where high signal yields are needed. We report on the methods developed for in-situ characterization and monitoring of DEAP's 255 R5912-HQE PMTs. This includes a detailed discussion of typical measured single-photoelectron charge distributions, correlated noise (afterpulsing), dark noise, double, and late pulsing characteristics. The characterization is performed during the detector commissioning phase using laser light injected through a light diffusing sphere and during normal detector operation using LED light injected through optical fibres