Soft gamma rays from low accreting supermassive black holes and connection to energetic neutrinos.

The Universe is filled with a diffuse background of MeV gamma-rays and PeV neutrinos, whose origins are unknown. Here, we propose a scenario that can account for both backgrounds simultaneously. Low-luminosity active galactic nuclei have hot accretion flows where thermal electrons naturally emit soft gamma rays via Comptonization of their synchrotron photons. Protons there can be accelerated via turbulence or reconnection, producing high-energy neutrinos via hadronic interactions. We demonstrate that our model can reproduce the gamma-ray and neutrino data. Combined with a contribution by hot coronae in luminous active galactic nuclei, these accretion flows can explain the keV - MeV photon and TeV - PeV neutrino backgrounds. This scenario can account for the MeV background without non-thermal electrons, suggesting a higher transition energy from the thermal to nonthermal Universe than expected. Our model is consistent with X-ray data of nearby objects, and testable by future MeV gamma-ray and high-energy neutrino detectors.

Hidden Cores of Active Galactic Nuclei as the Origin of Medium-Energy Neutrinos: Critical Tests with the MeV Gamma-Ray Connection.

Mysteries about the origin of high-energy cosmic neutrinos have deepened by the recent IceCube measurement of a large diffuse flux in the 10-100 TeV range. Based on the standard disk-corona picture of active galactic nuclei (AGN), we present a phenomenological model enabling us to systematically calculate the spectral sequence of multimessenger emission from the AGN coronae. We show that protons in the coronal plasma can be stochastically accelerated up to PeV energies by plasma turbulence, and find that the model explains the large diffuse flux of medium-energy neutrinos if the cosmic rays carry only a few percent of the thermal energy. We find that the Bethe-Heitler process plays a crucial role in connecting these neutrinos and cascaded MeV gamma rays, and point out that the gamma-ray flux can even be enhanced by the reacceleration of secondary pairs. Critical tests of the model are given by its prediction that a significant fraction of the MeV gamma-ray background correlates with ∼10 TeV neutrinos, and nearby Seyfert galaxies including NGC 1068 are promising targets for IceCube, KM3Net, IceCube-Gen2, and future MeV gamma-ray telescopes.

[Comparison of open and laparoscopic minor liver resections for malignant tumours - based on the experience of the first 50 cases]. / Malignus májdaganatok miatt végzett laparoszkópos minor reszekciók eredményei az elso 50 eset kapcsán.

INTRODUCTION: Laparoscopic resection of liver malignancies is gaining acceptance. Besides the advantages of minimally-invasive techniques, publications so far show no oncologic compromise of laparoscopy. AIM: Our aim was to compare the results of our first fifty laparoscopic minor liver resections with traditional open procedures. METHOD: We investigated laparoscopic and open minor liver resections performed in our institute between 01. 01. 2013 and 31. 03. 2017. Data were analysed retrospectively. Resection of maximum two segments was considered a minor resection. We compared the number of resected segments, intraoperative blood loss, operative time, 30 day morbidity and mortality, hospital stay, R1 resection ratio and resection margin width. RESULTS: During the given period, 123 open and 55 laparoscopic minor liver resections of malignant liver tumours were performed. Open and laparoscopic groups were similar considering age, sex and health status. The ratio of bi-segmentectomies was significantly higher in the open group (p<0.001). Operation time (p = 0.91) and peri-operative transfusion ratio did not differ in the two groups (p = 0.102). 30 day morbidity and mortality were consistent (p = 0.50; p = 0.34), but patients in the laparoscopic group spent shorter time in hospital (p = 0.0001). The average width of resection margins and the ratio of R1 resections showed no difference between open and laparoscopic groups (p = 0.447; p = 0.263). CONCLUSION: Our investigation indicates that in malignant liver tumours, laparoscopic resection significantly shortens hospital stay without oncologic compromise, even though 30 day morbidity and mortality does not show difference. We conclude that laparoscopic minor resection of malignant liver tumours is safe and feasible. Orv Hetil. 2019; 160(3): 104-111.

Laparoscoppal végzett subtotalis gyomorresectio Roux-en-Y szerinti rekonstrukcióval, antralis gyomoradenocarcinoma miatt.

UNLABELLED: A 35-year-old female presented with epigastric symptoms and fatigue. Gastroscopy revealed a 2 cm ulcerated lesion in the antrum region. Biopsy confirmed an invasive intestinal type adenocc. Staging CT and EUS: cT2cN0cM0. Laparoscopic subtotal gastric resection + modified D2 lymphadenectomy was performed with Roux-en-Y reconstruction of the alimentary tract. Mobilisation of the duodenum and stomach was performed with a 5 mm Ligasure. Distal and proximal resection was performed using Endo GIA 60 mm staplers. We performed a modified D1 lymphadenectomy including the region of the coeliac axis, splenic artery and the hepato-duodenal ligament. A side-to-side retrocolic loop gastro-jejunostomy was fashioned using Endo GIA. To transform the loop jejunostomy to a Roux-n-Y setting, the efferent loop of the jejunum was divided using Endo GIA, while the open end of the stomach was sealed with this same stapler line. This way, the loop anastomosis was fashioned into Roux-Y. The end-to-side jejuno-jejunostomy component of the Roux-Y anastomosis was performed through the specimen extraction site with hand-sewn technique. Duration of surgery: 200 min. Blood loss: 100 ml. The postop period was uneventful, and the patient was discharged on day 9. HISTOLOGY: Invasive intestinal type adenocc., 27 mm diameter, pT1bpN0, HER2 2+. DISCUSSION: Laparoscopic subtotal gastric resection with Roux-Y reconstruction is feasable without oncologic compromise and with excellent functional results in early gastric cancer.

Testing Einstein's Equivalence Principle With Fast Radio Bursts.

The accuracy of Einstein's equivalence principle (EEP) can be tested with the observed time delays between correlated particles or photons that are emitted from astronomical sources. Assuming as a lower limit that the time delays are caused mainly by the gravitational potential of the Milky Way, we prove that fast radio bursts (FRBs) of cosmological origin can be used to constrain the EEP with high accuracy. Taking FRB 110220 and two possible FRB/gamma-ray burst (GRB) association systems (FRB/GRB 101011A and FRB/GRB 100704A) as examples, we obtain a strict upper limit on the differences of the parametrized post-Newtonian parameter γ values as low as [γ(1.23 GHz)-γ(1.45 GHz)]<4.36×10(-9). This provides the most stringent limit up to date on the EEP through the relative differential variations of the γ parameter at radio energies, improving by 1 to 2 orders of magnitude the previous results at other energies based on supernova 1987A and GRBs.

[Metastatic malignant melanoma of the oesophagus: case report]. / Melanoma malignum nyelocso-metastasisának operált esete.

We report a case of metastatic malignant melanoma in the oesophagus. 13 years after the wide excision of primary skin melanoma, we found a polypoid tumor in the upper third of the oesophagus. Biopsy result was melanoma malignum. After negative staging we performed transhiatal oesophagectomy with gastric conduit and cervical anastomosis. Metastatic nature of the oesophageal tumor was proven by histology. After uneventful postoperative course, the patient received adjuvant dacarbazine treatment. The patient was is in good condition, and disease free on the 18 month follow-up.

Subphotospheric neutrinos from gamma-ray bursts: the role of neutrons.

Relativistic outflows with neutrons inevitably lead to inelastic collisions, and resulting subphotospheric γ rays may explain prompt emission of γ-ray bursts. In this model, hadronuclear, quasithermal neutrinos in the 10-100 GeV range should be generated, and they may even have a high-energy tail by neutron-proton-converter or shock acceleration mechanisms. We demonstrate the importance of dedicated searches with DeepCore+IceCube, though such analyses have not been performed. Successful detections enable us to discriminate among prompt emission mechanisms, probe the jet composition, and see roles of relativistic neutrons as well as effects of cosmic-ray acceleration.

Neutron-proton-converter acceleration mechanism at subphotospheres of relativistic outflows.

We study a type of particle acceleration that operates via neutron-proton conversion in inelastic nuclear collisions. This mechanism can be expected for relativistic shocks at subphotospheres if relativistic outflows contain neutrons. Using a test-particle approximation, we numerically calculate the energy spectrum and the efficiency of accelerated particles, and show that a good energy fraction of the nucleons can be accelerated. This mechanism may be especially relevant if the shock is radiation mediated, and it would enhance the detectability of GeV-TeV neutrinos.

The function of the ATP-binding cassette (ABC) transporter ABCB1 is not susceptible to actin disruption.

Previously we have shown that the activity of the multidrug transporter ABCC1 (multidrug resistance protein 1), and its localization in lipid rafts, depends on cortical actin (Hummel I, Klappe K, Ercan C, Kok JW. Mol. Pharm. 2011 79, 229-40). Here we show that the efflux activity of the ATP-binding cassette (ABC) family member ABCB1 (P-glycoprotein), did not depend on actin, neither in ABCB1 over expressing murine National Institutes of Health (NIH) 3T3 MDR1 G185 cells nor in human SK-N-FI cells, which endogenously express ABCB1. Disruption of the actin cytoskeleton, upon treatment of the cells with latrunculin B or cytochalasin D, caused severe changes in cell and membrane morphology, and concomitant changes in the subcellular distribution of ABCB1, as revealed by confocal laser scanning and electron microscopy. Nevertheless, irrespective of actin perturbation, the cell surface pool of ABCB1 remained unaltered. In NIH 3T3 MDR1 G185 cells, ABCB1 is partly localized in detergent-free lipid rafts, which partitioned in two different density gradient regions, both enriched in cholesterol and sphingolipids. Interestingly, disruption of the actin cytoskeleton did not change the density gradient distribution of ABCB1. Our data demonstrate that the functioning of ABCB1 as an efflux pump does not depend on actin, which is due to its distribution in both cell surface-localized non-raft membrane areas and lipid raft domains, which do not depend on actin stabilization.

Long term myriocin treatment increases MRP1 transport activity.

We investigated the effect of myriocin treatment, which extensively depletes sphingolipids from cells, on multidrug resistance-related protein 1 (MRP1) efflux activity in MRP1 expressing cells and isolated plasma membrane vesicles. Our data reveal that both short term (3 days) and long term (7 days) treatment effectively reduce the cellular sphingolipid content to the same level. Intriguingly, a two-fold increase in MRP1-mediated efflux activity was observed following long term treatment, while short term treatment had no impact. Very similar data were obtained with plasma membrane vesicles isolated from myriocin-treated cells. Exploiting the cell-free vesicle system, Michaelis-Menten analysis revealed that the intrinsic MRP1 activity remained unaltered; however, the fraction of active transporter molecules increased. We demonstrate that the latter effect is due to an enhanced recruitment of MRP1 into lipid raft fractions, thereby promoting MRP1 activity.

Gamma-ray bursts.

Gamma-ray bursts (GRBs) are bright flashes of gamma rays coming from the cosmos. They occur roughly once per day, typically last for tens of seconds, and are the most luminous events in the universe. More than three decades after their discovery, and after pioneering advances from space and ground experiments, they still remain mysterious. The launch of the Swift and Fermi satellites in 2004 and 2008 brought in a trove of qualitatively new data. In this Review, we survey the interplay between these recent observations and the theoretical models of the prompt GRB emission and the subsequent afterglow.

The toolbox of vesicle sidedness determination.

Vesicles prepared from cellular plasma membranes are widely used in science for different purposes. The outer membrane leaflet differs from the inner membrane leaflet of the vesicle, and during vesicle preparation procedures two types of vesicles will be generated: right-side-out vesicles, of which the outer leaflet is topologically equivalent to the outer monolayer of the cellular plasma membrane, and inside-out vesicles. Because two populations of vesicles exist, sidedness information of the vesicle preparation is indispensable. This note focuses on the ins and outs of sidedness determination of vesicles and compares various methodologies used to establish this ratio.

Function of MRP1/ABCC1 is not dependent on cholesterol or cholesterol-stabilized lipid rafts.

MRP1 (multidrug-resistance-related protein 1)/ABCC1 (ATP-binding cassette transporter C1) has been localized in cholesterol-enriched lipid rafts, which suggests a role for these lipid rafts and/or cholesterol in MRP1 function. In the present study, we have shown for the first time that nearly complete oxidation of free cholesterol in the plasma membrane of BHK-MRP1 (MRP1-expressing baby hamster kidney) cells did not affect MRP1 localization in lipid rafts or its efflux function, using 5-carboxyfluorescein diacetate as a substrate. Inhibition of cholesterol biosynthesis, using lovastatin in combination with RO 48-8071, an inhibitor of oxidosqualene cyclase, resulted in a shift of MRP1 out of lipid raft fractions, but did not affect MRP1-mediated efflux in Neuro-2a (neuroblastoma) cells. Short-term methyl-ß-cyclodextrin treatment was equally effective in removing free cholesterol from Neuro-2a and BHK-MRP1 cells, but affected MRP1 function only in the latter. The kinetics of loss of both MRP1 efflux function and lipid raft association during long-term methyl-ß-cyclodextrin treatment did not match the kinetics of free cholesterol removal in both cell lines. Moreover, MRP1 activity was measured in vesicles consisting of membranes isolated from BHK-MRP1 cells using the substrate cysteinyl leukotriene C4 and was not changed when the free cholesterol level of these membranes was either decreased or increased. In conclusion, MRP1 activity is not correlated with the level of free cholesterol or with localization in cholesterol-dependent lipid rafts.

Gamma-ray bursts prompt emission spectrum: an analysis of a photosphere model.

A thermal radiative component is likely to accompany the first stages of the prompt emission of gamma-ray bursts (GRBs) and X-ray flashes. We analyse the effect of such a component on the observable spectrum, assuming that the observable effects are due to a dissipation process occurring below or near the thermal photosphere. For comparable energy densities in the thermal and leptonic components, the dominant emission mechanism is Compton scattering. This leads to a nearly flat energy spectrum (nuFnu proportional, 0) above the thermal peak at approximately 10-100 keV and below 10-100 MeV, for a wide range of optical depths 0.03 less, similar tau less, similar 100, regardless of the details of the dissipation mechanism or the strength of the magnetic field. For higher values of the optical depth, a Wien peak is formed at 100 keV to 1 MeV. In particular, these results are applicable to the internal shock model of GRBs, as well as to slow dissipation models, e.g. as might be expected from reconnection, if the dissipation occurs at a sub-photospheric radii. We conclude that dissipation near the thermal photosphere can naturally explain (i) clustering of the peak energy at sub-MeV energies at early times, (ii) steep slopes observed at low energies, and (iii) a flat spectrum above 10 keV at late times. Our model thus provides an alternative scenario to the optically thin synchrotron-synchrotron self-Compton model.

[In vitro methods suitable for the prediction of drug and ABC transporter, especially ABCG2 interactions]. / ABC transzporterek-különös tekintettel az ABCG2-re--és gyógyszerjelölt molekulák kölcsönhatásának predikciójára alkalmas in vitro módszerek.

ABCG2, a transporter of the ATP-binding cassette family, is known to play a prominent role in the absorption, distribution, metabolism, and excretion of xenobiotics. Drug-transporter interactions are commonly screened by in vitro systems using transfected insect and/or human cell lines.

TeV neutrinos from core collapse supernovae and hypernovae.

A fraction of core-collapse supernovae of type Ib/c are associated with gamma-ray bursts, which are thought to produce highly relativistic jets. Recently, it has been hypothesized that a larger fraction of core-collapse supernovae produce slower jets, which may contribute to the disruption and ejection of the supernova envelope, and explain the unusually energetic hypernovae. We explore the TeV neutrino signatures expected from such slower jets, and calculate the expected detection rates with upcoming Gigaton Cherenkov experiments. We conclude that individual jetted supernovae may be detectable from nearby galaxies.

High energy neutrinos from gamma-ray bursts with precursor supernovae.

The high energy neutrino signature from proton-proton and photo-meson interactions in a supernova remnant shell ejected prior to a gamma-ray burst provides a test for the precursor supernova, or supranova, model of gamma-ray bursts. Protons in the supernova remnant shell and photons entrapped from a supernova explosion or a pulsar wind from a fast-rotating neutron star remnant provide ample targets for protons escaping the internal shocks of the gamma-ray burst to interact and produce high energy neutrinos. We calculate the expected neutrino fluxes, which can be detected by current and future experiments.