Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.

SS 433 is a binary system containing a supergiant star that is overflowing its Roche lobe with matter accreting onto a compact object (either a black hole or neutron star)1-3. Two jets of ionized matter with a bulk velocity of approximately 0.26c (where c is the speed of light in vacuum) extend from the binary, perpendicular to the line of sight, and terminate inside W50, a supernova remnant that is being distorted by the jets2,4-8. SS 433 differs from other microquasars (small-scale versions of quasars that are present within our own Galaxy) in that the accretion is believed to be super-Eddington9-11, and the luminosity of the system is about 1040 ergs per second2,9,12,13. The lobes of W50 in which the jets terminate, about 40 parsecs from the central source, are expected to accelerate charged particles, and indeed radio and X-ray emission consistent with electron synchrotron emission in a magnetic field have been observed14-16. At higher energies (greater than 100 gigaelectronvolts), the particle fluxes of γ-rays from X-ray hotspots around SS 433 have been reported as flux upper limits6,17-20. In this energy regime, it has been unclear whether the emission is dominated by electrons that are interacting with photons from the cosmic microwave background through inverse-Compton scattering or by protons that are interacting with the ambient gas. Here we report teraelectronvolt γ-ray observations of the SS 433/W50 system that spatially resolve the lobes. The teraelectronvolt emission is localized to structures in the lobes, far from the centre of the system where the jets are formed. We have measured photon energies of at least 25 teraelectronvolts, and these are certainly not Doppler-boosted, because of the viewing geometry. We conclude that the emission-from radio to teraelectronvolt energies-is consistent with a single population of electrons with energies extending to at least hundreds of teraelectronvolts in a magnetic field of about 16 microgauss.

Publisher Correction: Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.

In this Letter, owing to a production error, the penultimate version of the PDF was published. The HTML version was always correct. The PDF has been corrected online.

Discovery of Gamma Rays from the Quiescent Sun with HAWC.

We report the first detection of a TeV γ-ray flux from the solar disk (6.3σ), based on 6.1 years of data from the High Altitude Water Cherenkov (HAWC) observatory. The 0.5-2.6 TeV spectrum is well fit by a power law, dN/dE=A(E/1 TeV)^{-γ}, with A=(1.6±0.3)×10^{-12} TeV^{-1} cm^{-2} s^{-1} and γ=3.62±0.14. The flux shows a strong indication of anticorrelation with solar activity. These results extend the bright, hard GeV emission from the disk observed with Fermi-LAT, seemingly due to hadronic Galactic cosmic rays showering on nuclei in the solar atmosphere. However, current theoretical models are unable to explain the details of how solar magnetic fields shape these interactions. HAWC's TeV detection thus deepens the mysteries of the solar-disk emission.

Constraints on Lorentz Invariance Violation from HAWC Observations of Gamma Rays above 100 TeV.

Because of the high energies and long distances to the sources, astrophysical observations provide a unique opportunity to test possible signatures of Lorentz invariance violation (LIV). Superluminal LIV enables the decay of photons at high energy. The high altitude water Cherenkov (HAWC) observatory is among the most sensitive gamma-ray instruments currently operating above 10 TeV. HAWC finds evidence of 100 TeV photon emission from at least four astrophysical sources. These observations exclude, for the strongest of the limits set, the LIV energy scale to 2.2×10^{31} eV, over 1800 times the Planck energy and an improvement of 1 to 2 orders of magnitude over previous limits.

Multiple Galactic Sources with Emission Above 56 TeV Detected by HAWC.

We present the first catalog of gamma-ray sources emitting above 56 and 100 TeV with data from the High Altitude Water Cherenkov Observatory, a wide field-of-view observatory capable of detecting gamma rays up to a few hundred TeV. Nine sources are observed above 56 TeV, all of which are likely galactic in origin. Three sources continue emitting past 100 TeV, making this the highest-energy gamma-ray source catalog to date. We report the integral flux of each of these objects. We also report spectra for three highest-energy sources and discuss the possibility that they are PeVatrons.

Early outcome of a 31-gene expression profile test in 86 AJCC stage IB-II melanoma patients. A prospective multicentre cohort study.

BACKGROUND: The clinical and pathological features of primary melanoma are not sufficiently sensitive to accurately predict which patients are at a greater risk of relapse. Recently, a 31-gene expression profile (DecisionDx-Melanoma) test has shown promising results. OBJECTIVES: To evaluate the early prognostic performance of a genetic signature in a multicentre prospectively evaluated cohort. METHODS: Inclusion of patients with AJCC stages IB and II conducted between April 2015 and December 2016. All patients were followed up prospectively to assess their risk of relapse. Prognostic performance of this test was evaluated individually and later combined with the AJCC staging system. Prognostic accuracy of disease-free survival was determined using Kaplan-Meier curves and Cox regression analysis. Results of the gene expression profile test were designated as Class 1 (low risk) and Class 2 (high risk). RESULTS: Median follow-up time was 26 months (IQR 22-30). The gene expression profile test was performed with 86 patients; seven had developed metastasis (8.1%) and all of them were in the Class 2 group, representing 21.2% of this group. Gene expression profile was an independent prognostic factor for relapse as indicated by multivariate Cox regression analysis, adjusted for AJCC stages and age. CONCLUSIONS: This prospective multicentre cohort study, performed in a Spanish Caucasian cohort, shows that this 31-gene expression profile test could correctly identify patients at early AJCC stages who are at greater risk of relapse. We believe that gene expression profile in combination with the AJCC staging system could well improve the detection of patients who need intensive surveillance and optimize follow-up strategies.

Development and validation of an alternative procedure for quantitative quality control analysis of 99mTc-radiopharmaceuticals using a Geiger Müller counter.

BACKGROUND AND OBJECTIVES: In a hospital radiopharmacy with 2a operational level, including the preparation of radiopharmaceuticals from prepared and approved reagent kits, it is common to have a single activimeter or dose calibrator for labeling and fractionation, and to perform the quality controls of the 99mTc-radiopharmaceuticals. In certain cases, the accumulation of radioactive material or accidental contamination of the work area causes the background to exceed the limits to carry out the radiochemical purity analyses and it is necessary to look for viable alternatives. In this work, a Geiger Müller detector (equipped with a probe for measuring surface contamination) frequently used for radioprotection purposes, was validated as an alternative and its performance was compared against the activimeter for 99mTc-radiopharmaceuticals. MATERIALS AND METHODS: Using [99mTc]pertechnetate, systematic studies of error analyses and detector response to activity concentration, activity and measurement time were carried out in liquid matrices and in paper. The results were compared against an activimeter calibrated for [99mTc]Tc. RESULTS: The developed method was used to determine the radiochemical purity of the compounds [99mTc]Tc-MDP and [99mTc]Tc-MIBI by ascending paper chromatography tests, obtaining comparable values to those measured with an activimeter in the same system (within 1% uncertainty) and using the method of vial partitioning in a dedicated equipment. CONCLUSIONS: This work demonstrates that a Geiger Müller detector with a probe for measuring surface contamination can be adequately used to replace other equipment in the control of radiochemical purity in the hospital radiopharmacy.

Use of Arabidopsis thaliana to study mechanisms of control of Verticillium wilt by Pseudomonas fluorescens PICF7.

Verticillium wilt (VW), caused by Verticillium dahliae Kleb., is an important disease in many crops and its effective management has proven difficult. Among the various disease control measures to be implemented, the use of microbial antagonists (biological control agents, BCAs) constitutes an environmentally-friendly approach fitting criteria of modern sustainable agriculture. Pseudomonas fluorescens PICF7 was isolated from root tissues of nursery--propagated olive plants. Selection of this strain was based on in vitro growth inhibition of V. dahliae, colonizing ability of olive roots, endophytic lifestyle, and control of the highly-virulent defoliating (D) pathotype of V. dahliae in olive planting stocks. The mode of action by which PICF7 controls VW in olive is as yet unknown; moreover, to uncover potential biocontrol mechanisms poses additional difficulties in this pathosystem because the target is a tree. Therefore we used the model plant Arabidopsis thaliana to study: i) if PICF7 colonizes the rhizosphere of A. thaliana; ii) disease symptoms caused by V. dahliae in A. thaliana; iii) control of VW by PICF7 in different accessions and mutants of A. thaliana; and iv) if motility, antibiosis and/or siderophores are involved in control of V. dahliae by PICF7. Diverse bioassays were conducted and in all of them both the BCA and the pathogen were introduced in the rhizosphere of A. thaliana. Both D and non-defoliating isolates of V. dahliae caused disease symptoms in A. thaliana. PICF7 colonized and persisted in the rhizosphere of different Arabidopsis accessions and could control the D pathotype in some of them. PICF7 mutants affected in antibiosis significantly lost their ability to control VW in A. thaliana. We conclude that the model plant A. thaliana is useful to unravel interactions between this BCA and V. dahliae.

Genetic diversity of Chlamydia pecorum detected in sheep flocks from Mexico.

Chlamydia pecorum, an obligate intracellular bacterium, is associated with reproductive and systemic diseases in sheep, goats, pigs, cattle, and koalas. The main conditions include polyarthritis, conjunctivitis, enteritis, pneumonia, encephalomyelitis, orchitis, placentitis, and abortion. Even though there are several studies showing that C. pecorum infections are widely spread in the world, in Mexico there are no reports. During 2016, as part of a sheep restocking program in Mexico, sheep were imported from New Zealand. Briefly after their arrival in the herds in the State of Mexico, these sheep presented abortions during the last third of gestation. A total of 62 sheep vaginal swabs that had presented abortion from different municipalities of the State of Mexico were collected. Bacterial isolation was performed using L929 mouse fibroblasts, and molecular identification was achieved by 23S rRNA (Chlamydiaceae family) and ompA gene (species-specific) real-time polymerase chain reaction (PCR). In addition, the 16S rRNA subunit and ompA gene were amplified and sequenced. Seven of 62 samples were positive for C. pecorum by bacterial isolation, 23S rRNA, and ompA gene real-time PCR. The 16S rRNA subunit and ompA gene amplicons were purified and the nucleotide sequence was determined in both directions. The consensus sequences homology search was performed using BLASTn analysis and showed a 100% of homology with the C. pecorum 16S rRNA subunit and 99% with the C. pecorum ompA gene. The population structure analyses using ompA gene demonstrated 15 genetic populations or clusters of 198 sequences from GenBank and our sequences were in a particular genetic structure corresponding to genotype "O." Herein, we describe the presence of C. pecorum in sheep imported from New Zealand into Mexico. Genetic analysis of the ompA gene showed that the isolates belong to genotype O and are related to strains isolated from sheep, cattle, and koalas.

Acid leaching of LiCoO2 enhanced by reducing agent. Model formulation and validation.

In this work, a model has been formulated to describe the complex process of LiCoO2 leaching through the participation of competing reactions in acid media including the effect of H2O2 as reducing agent. The model presented here describes the extraction of Li and Co in the presence and absence of H2O2, and it takes into account the different phenomena affecting the controlling mechanisms. In this context, the model predicts the swift from kinetic control to diffusion control. The model has been implemented and solved to simulate the leaching process. To validate the model and to estimate the model parameters, a set of 12 (in triplicate) extraction experiments were carried out varying the concentration of hydrochloric acid (within the range of 0.5-2.5 M) and hydrogen peroxide (range 0-0.6%v/v). The simulation results match fairly well with the experimental data for a wide range of conditions. Furthermore, the model can be used to predict results with different solid-liquid ratios as well as different acid and oxygen peroxide concentrations. This model could be used to design or optimize a LiCoO2 extraction process facilitating the corresponding economical balance of the treatment.

Plitidepsin as a successful rescue treatment for prolonged viral SARS-CoV-2 replication in a patient with previous anti-CD20 monoclonal antibody-mediated B cell depletion and chronic lymphocytic leukemia.

BACKGROUND: There is an urgent need for highly efficacious antiviral therapies in immunosuppressed hosts who develop coronavirus disease (COVID-19), with special concern for those affected by hematological malignancies. CASE PRESENTATION: Here, we report the case of a 75-year-old male with chronic lymphocytic leukemia who was deficient in CD19+CD20+ B-lymphocyte populations due to previous treatment with anti-CD20 monoclonal antibodies. The patient presented with severe COVID-19 pneumonia due to prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and was treated with two courses of the antiviral plitidepsin on a compassionate use basis. The patient subsequently achieved an undetectable viral load, and his pneumonia resolved. CONCLUSIONS: Treatment with plitidepsin was well-tolerated without any further hematological or cardiovascular toxicities. This case further supports plitidepsin as a potential antiviral drug in SARS-CoV-2 patients affected by immune deficiencies and hematological malignancies.

Light deprivation damages monoamine neurons and produces a depressive behavioral phenotype in rats.

Light is an important environmental factor for regulation of mood. There is a high frequency of seasonal affective disorder in high latitudes where light exposure is limited, and bright light therapy is a successful antidepressant treatment. We recently showed that rats kept for 6 weeks in constant darkness (DD) have anatomical and behavioral features similar to depressed patients, including dysregulation of circadian sleep-waking rhythms and impairment of the noradrenergic (NA)-locus coeruleus (LC) system. Here, we analyzed the cell viability of neural systems related to the pathophysiology of depression after DD, including NA-LC, serotoninergic-raphe nuclei and dopaminergic-ventral tegmental area neurons, and evaluated the depressive behavioral profile of light-deprived rats. We found increased apoptosis in the three aminergic systems analyzed when compared with animals maintained for 6 weeks in 12:12 light-dark conditions. The most apoptosis was observed in NA-LC neurons, associated with a significant decrease in the number of cortical NA boutons. Behaviorally, DD induced a depression-like condition as measured by increased immobility in a forced swim test (FST). DD did not appear to be stressful (no effect on adrenal or body weights) but may have sensitized responses to subsequent stressors (increased fecal number during the FST). We also found that the antidepressant desipramine decreases these neural and behavioral effects of light deprivation. These findings indicate that DD induces neural damage in monoamine brain systems and this damage is associated with a depressive behavioral phenotype. Our results suggest a mechanism whereby prolonged limited light intensity could negatively impact mood.

Placental FTO expression relates to fetal growth.

OBJECTIVE: The fat mass and obesity-associated gene (FTO) participates in the control of postnatal weight gain. We assessed whether FTO is expressed in human placenta and whether such expression relates to prenatal weight gain and to the rs9939609 single nucleotide polymorphism (SNP) in FTO. DESIGN AND SUBJECTS: In a birth cohort study, placentas from women (n = 147) with an uncomplicated, singleton, term pregnancy were weighed at delivery. Real-time PCR was used to study, in placental tissue, the expression of FTO and of housekeeping genes (TATA box binding protein and succinate dehydrogenase complex, subunit A) and to genotype the rs9939609 SNP in FTO. Weights and lengths of the newborns were measured; circulating insulin and insulin-like growth factor-I (IGF-I) were quantified in cord blood. RESULTS: FTO was highly expressed in placenta and was associated with increased fetal weight and length (P<0.001 to P<0.0001). Maternal parity showed an interaction (P<0.001) in the association between placental FTO expression and placental weight. Placental FTO mRNA expression was associated with increased fetal-to-placental weight ratio (P<0.005) in infants from primiparous women, and was associated with increased fetal weight and length and placental weight (P<0.001 to P<0.0001) in infants from nonprimiparous women. These associations were not explained by either cord insulin or IGF-I. Placental FTO expression was unrelated to placental FTO rs9939609 SNP. CONCLUSION: FTO is expressed in the human placenta. In a maternal parity-dependent manner, placental FTO may participate either in the control of fetal weight gain or in the partitioning between placental and fetal growth.

Transanal rectocele repair using linear stapler and bioabsorbable staple line reinforcement material: short-term results of a prospective study.

PURPOSE: This study was designed to determine the short-term results of transanal rectocele repair with use of a linear stapler and Bioabsorbable Seamguard. METHODS: Ten women (median age, 56.1 y) with obstructed defecation syndrome were enrolled in the study. The preoperative study consisted of a medical history, physical examination, anoscopy, endoanal ultrasound, and defecography. All patients completed a severity score and a visual analog scale for global quality of life, and provided the postoperative dates of complications. RESULTS: Overall, the treatment significantly improved the obstructed defecation: the severity score improved from a median of 19.8 +/- 4.2 at baseline to 6.10 +/- 8.2 at one month (P < .005), 5.9 +/- 8.3 at 6 months (P < .005), and 6 +/- 8.3 at one year after the operation (P < .005). A significant improvement was observed in the visual analog scale, which improved from a median of 1.8 +/- 1.4 at baseline to 6 +/- 1.6 at one month (P < .005), 6.6 +/- 2.1 at 6 months (P < .004), and 7 +/- 2.5 at one year (P < .004). A significant improvement was also observed in various symptoms. Only 2 patients manifested urgent defecation. CONCLUSIONS: The present study demonstrates that rectocele repair using a linear stapler and Seamguard is a safe, easy procedure, with a very low rate of complications and good immediate outcome.

Method for the simultaneous determination of the most problematic families of organic pollutants in compost and compost-amended soil.

Linear alkylbenzene sulfonates (LAS), nonylphenol ethoxylates (NPE; sum of nonylphenol, nonylphenol monoethoxylate, and nonylphenol diethoxylate), and di-(2-ethylhexyl)phthalate (DEHP) are the most problematic organic pollutants in sludge owing to their high concentrations and the concentration limits of 2,600, 50, and 100 mg/kg, respectively, proposed in the European Union directive draft for land application of sludge. In this paper, an analytical method for the simultaneous determination of the C(10), C(11), C(12), and C(13) LAS homologues, the nonylphenolic compounds nonylphenol, nonylphenol monoethoxylate, and nonylphenol diethoxylate, and di(2-ethylhexyl)phthalate in compost and compost-amended soil is proposed. The method is based on sonication-assisted extraction, cleanup by solid-phase extraction, and determination by high-performance liquid chromatography with diode-array and fluorescence detectors. The mean recoveries of LAS, NPE, and DEHP were 83, 87, and 79%, respectively, in compost samples, and 77, 96, and 99%, respectively, in compost-amended soil samples. The limits of detection and quantification in compost samples were lower than 6.77 and 22.3 mg/kg dry matter, respectively, for LAS; lower than 7.34 and 22.8 mg/kg dry matter, respectively, for NPE; and 0.78 and 1.18 mg/kg dry matter, respectively, for DEHP. The limits of detection and quantification in compost-amended soil samples were lower than 0.03 and 0.10 mg/kg dry matter, respectively, for LAS; lower than 0.04 and 0.12 mg/kg dry matter, respectively, for NPE; and 0.03 and 0.10 mg/kg dry matter, respectively, for DEHP. The method was successfully applied to compost and compost-amended soil samples from Seville (south of Spain).

A gamma-ray burst with a high-energy spectral component inconsistent with the synchrotron shock model.

Gamma-ray bursts are among the most powerful events in nature. These events release most of their energy as photons with energies in the range from 30 keV to a few MeV, with a smaller fraction of the energy radiated in radio, optical, and soft X-ray afterglows. The data are in general agreement with a relativistic shock model, where the prompt and afterglow emissions correspond to synchrotron radiation from shock-accelerated electrons. Here we report an observation of a high-energy (multi-MeV) spectral component in the burst of 17 October 1994 that is distinct from the previously observed lower-energy gamma-ray component. The flux of the high-energy component decays more slowly and its fluence is greater than the lower-energy component; it is described by a power law of differential photon number index approximately -1 up to about 200 MeV. This observation is difficult to explain with the standard synchrotron shock model, suggesting the presence of new phenomena such as a different non-thermal electron process, or the interaction of relativistic protons with photons at the source.

Development of a structured sensory honey analysis: application to artisanal Madrid honeys.

In this work a methodology to evaluate the sensory properties of honeys has been developed. The sensory analysis was carried out by means of a quantitative descriptive analysis (QDA) method, based on several reference scales, for the coverage of the designed range for each descriptor. The peculiarity of this sensory analysis is that the reference scales have been constituted by common foodstuffs agreed upon by consensus of the panel. The main sensory attributes evaluated in the analyses were: adhesiveness, viscosity, bitterness, aroma, sweetness, acidity, color and granularity. Both the intensity and persistence of honey aromas have also been estimated, together with the classification of the identified aromatic attributes into different groups. The method was applied to 55 artisanal honeys from Madrid (Spain) with the following results: (i) the developed sensory profile sheet allowed a satisfactory description of Madrid honeys; (ii) correlations between sensory attributes of three broad groups of Madrid honeys were obtained and (iii) aroma persistence, sweetness, bitterness, color and granularity appeared as the main sensorial characteristics of honey with discrimination power between floral and honeydew honeys.

Alpha-1-acid glycoprotein, its local production and immunopathological participation in experimental pulmonary tuberculosis.

Alpha-1-acid glycoprotein (AGP) is one of the major acute-phase proteins (APPs). Hepatic production and serum concentrations increase in response to systemic injury, inflammation, or infection. We reported previously that expression of the AGP gene is induced in the liver during experimental pulmonary tuberculosis. Since AGP may also be produced at the infection site and has some immunomodulatory properties, we used a model of progressive pulmonary tuberculosis in Balb/c mice to study the kinetics of AGP production in the lung and its influence on immunopathology. We found that AGP was produced in the lung during experimental tuberculosis. Alveolar macrophages and type II pneumocytes were the most important cellular sources during early infection (days 1-14). From day 21 postinfection, during the progressive phase of the infection, foamy macrophages located in pneumonic areas were the most important source of AGP and 10-fold higher concentrations were found on day 60. In a second part of the study, AGP was inactivated during the progressive phase by the administration of specific blocking antibodies. In comparison with control infected animals, tuberculous mice treated with blocking AGP antibodies showed higher expression of interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) in association with significantly reduced bacillary loads and tissue damage. Thus, AGP is produced in the lung during experimental pulmonary tuberculosis and it has immunomodulatory activities, suppressing cell-mediated immunity and facilitating growth of bacilli and disease progression.

Electronic density distribution of Mn-N bonds by a tuning effect through partial replacement of Mn by Co or Ni in a sodium-rich hexacyanoferrate and its influence on the stability as a cathode for Na-ion batteries.

This study evaluates the effect of equimolar substitution of manganese by cobalt or nickel in hexacyanoferrate (HCF) open frameworks as electrode materials for Na-ion batteries. As the stability of Mn-N bonds is crucial to obtain long term stability and cyclability of manganese (Mn-HCF), the samples were analyzed thoroughly using several spectroscopic and structural methods. The XPS and infrared experiments reveal that the charge density around Fe is modulated by the presence of Co or Ni, which is associated with their high polarizing power, leading to decreased cell distortion as revealed by XRD. The Rietveld refinement demonstrated that the octahedra built by 3d metals and the cyanide nitrogen were distorted with the axial bond distances being larger than the equatorial distances. This octahedral distortion promotes the spin behavior of 3/2 for Mn2+ confirmed by magnetic experiments; the arising of this spin state is attributed to d orbital splitting determined by UV-Vis experiments. Therefore, the changes upon Mn substitution are related to the modification of the covalent character of Mn-N bonds, modulated by the effect of the Ni and Co polarizing power. All these properties improve the electrochemical stability of the Ni or Co substituted materials as Na-ion batteries, leading to higher capacity retention even at higher C-rates (5C) and good capacity recovery, in comparison with those obtained for Mn-HCF.

Extended gamma-ray sources around pulsars constrain the origin of the positron flux at Earth.

The unexpectedly high flux of cosmic-ray positrons detected at Earth may originate from nearby astrophysical sources, dark matter, or unknown processes of cosmic-ray secondary production. We report the detection, using the High-Altitude Water Cherenkov Observatory (HAWC), of extended tera-electron volt gamma-ray emission coincident with the locations of two nearby middle-aged pulsars (Geminga and PSR B0656+14). The HAWC observations demonstrate that these pulsars are indeed local sources of accelerated leptons, but the measured tera-electron volt emission profile constrains the diffusion of particles away from these sources to be much slower than previously assumed. We demonstrate that the leptons emitted by these objects are therefore unlikely to be the origin of the excess positrons, which may have a more exotic origin.