Search for Gamma-Ray Spectral Lines from Dark Matter Annihilation up to 100 TeV toward the Galactic Center with MAGIC.

Linelike features in TeV γ rays constitute a "smoking gun" for TeV-scale particle dark matter and new physics. Probing the Galactic Center region with ground-based Cherenkov telescopes enables the search for TeV spectral features in immediate association with a dense dark matter reservoir at a sensitivity out of reach for satellite γ-ray detectors, and direct detection and collider experiments. We report on 223 hours of observations of the Galactic Center region with the MAGIC stereoscopic telescope system reaching γ-ray energies up to 100 TeV. We improved the sensitivity to spectral lines at high energies using large-zenith-angle observations and a novel background modeling method within a maximum-likelihood analysis in the energy domain. No linelike spectral feature is found in our analysis. Therefore, we constrain the cross section for dark matter annihilation into two photons to ⟨σv⟩≲5×10^{-28} cm^{3} s^{-1} at 1 TeV and ⟨σv⟩≲1×10^{-25} cm^{3} s^{-1} at 100 TeV, achieving the best limits to date for a dark matter mass above 20 TeV and a cuspy dark matter profile at the Galactic Center. Finally, we use the derived limits for both cuspy and cored dark matter profiles to constrain supersymmetric wino models.

Bounds on Lorentz Invariance Violation from MAGIC Observation of GRB 190114C.

On January 14, 2019, the Major Atmospheric Gamma Imaging Cherenkov telescopes detected GRB 190114C above 0.2 TeV, recording the most energetic photons ever observed from a gamma-ray burst. We use this unique observation to probe an energy dependence of the speed of light in vacuo for photons as predicted by several quantum gravity models. Based on a set of assumptions on the possible intrinsic spectral and temporal evolution, we obtain competitive lower limits on the quadratic leading order of speed of light modification.

Influence of ovarian cancer type I and type II microenvironment on the phenotype and function of monocyte-derived dendritic cells

PURPOSE. The aim of this study was to evaluate the influence of ovarian cancer cell lysates isolated from type I or type II ovarian cancer (OC) on the phenotype of monocyte-derived dendritic cells (Mo-DCs) and the cytokine profile. We also determined whether the Mo-DCs and tumor microenvironment, reflected by peritoneal fluid (PF) from type I or II ovarian cancer, could promote regulatory T cell (Tregs) differentiation from naive CD4+ lymphocytes in vitro. RESULTS. Our results show a significant role of the ovarian cancer microenvironment reflected by PF from type I or II OC in the inhibition of the DC differentiation process. Interestingly, the percentage of cells co-expressing CD45 and CD14 antigens in the cultures stimulated with PF from both type I and type II OC was higher than in the control. Furthermore, the percentage of cells expressing CD1a, i.e., a marker of immature DCs, was significantly reduced in the cultures stimulated with PF from type I and type II OC. The results obtained show that ovarian cancer type II lysates induce differentiation of monocytes into macrophage-like cells with a CD1a+/HLA-DR+/CD83− phenotype and significantly higher CD86/HLA-DR expression. We show that ovarian cancer type II Mo-DCs are able to prevent an immune response by release of IL-10, whereas OC type I Mo-DCs can promote the generation of Tregs. CONCLUSIONS. We demonstrate that each type of ovarian cancer can induce a unique phenotype of DCs and differentiation of Tregs, both associated with immune-suppressive function, which may be an obstacle while developing effective anticancer dendritic cell vaccination (AU)

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Influence of ovarian cancer type I and type II microenvironment on the phenotype and function of monocyte-derived dendritic cells.

PURPOSE: The aim of this study was to evaluate the influence of ovarian cancer cell lysates isolated from type I or type II ovarian cancer (OC) on the phenotype of monocyte-derived dendritic cells (Mo-DCs) and the cytokine profile. We also determined whether the Mo-DCs and tumor microenvironment, reflected by peritoneal fluid (PF) from type I or II ovarian cancer, could promote regulatory T cell (Tregs) differentiation from naive CD4+ lymphocytes in vitro. RESULTS: Our results show a significant role of the ovarian cancer microenvironment reflected by PF from type I or II OC in the inhibition of the DC differentiation process. Interestingly, the percentage of cells co-expressing CD45 and CD14 antigens in the cultures stimulated with PF from both type I and type II OC was higher than in the control. Furthermore, the percentage of cells expressing CD1a, i.e., a marker of immature DCs, was significantly reduced in the cultures stimulated with PF from type I and type II OC. The results obtained show that ovarian cancer type II lysates induce differentiation of monocytes into macrophage-like cells with a CD1a+/HLA-DR+/CD83- phenotype and significantly higher CD86/HLA-DR expression. We show that ovarian cancer type II Mo-DCs are able to prevent an immune response by release of IL-10, whereas OC type I Mo-DCs can promote the generation of Tregs. CONCLUSIONS: We demonstrate that each type of ovarian cancer can induce a unique phenotype of DCs and differentiation of Tregs, both associated with immune-suppressive function, which may be an obstacle while developing effective anticancer dendritic cell vaccination.

Macrophage-derived chemokine CCL22 and regulatory T cells in ovarian cancer patients.

The study was undertaken to evaluate macrophage-derived chemokine (CCL22) levels in the peritoneal fluid (PF) and plasma of patients with ovarian cancer (n = 93) in relation to regulatory T cells (Tregs; n = 75). The peritoneal fluid CCL22 concentrations were significantly higher in epithelial ovarian cancer (EOC) patients than in patients with benign tumors-serous cystadenoma (n = 32). There was no difference in plasma levels of CCL22 in EOC patients compared with the non-cancer and healthy volunteers (n = 10). There were no significant differences in the plasma and PF CCL22 levels based on tumor grade. However, women with stage IV FIGO (International Federation of Gynecologists and Obstetricians) had significantly higher plasma CCL22 levels than patients with stages I and III. Women with stage I FIGO had significantly higher PF CCL22 levels than patients with stages II and III. Women with endometrioid cystadenocarcinoma had higher PF CCL22 levels than women with undifferentiated carcinoma. The percentage of tumor-infiltrating Tregs (11.06 %) was significantly higher compared to PF (3.05 %) and peripheral blood (PB) (2.01 %). Moreover, the percentage of Tregs was higher in the PF than in the PB of EOC patients. There were no significant differences in the PB, PF, and tumor-infiltrating Tregs percentage based on tumor stage, grade, or histology. Elevated levels of CCL22 found in the ascites could create a chemokine gradient aiding in Treg cells migration. Increased Tregs percentage in the local microenvironment of ovarian cancer might be an important mechanism of immunosuppression.

Black hole physics. Black hole lightning due to particle acceleration at subhorizon scales.

Supermassive black holes with masses of millions to billions of solar masses are commonly found in the centers of galaxies. Astronomers seek to image jet formation using radio interferometry but still suffer from insufficient angular resolution. An alternative method to resolve small structures is to measure the time variability of their emission. Here we report on gamma-ray observations of the radio galaxy IC 310 obtained with the MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov) telescopes, revealing variability with doubling time scales faster than 4.8 min. Causality constrains the size of the emission region to be smaller than 20% of the gravitational radius of its central black hole. We suggest that the emission is associated with pulsar-like particle acceleration by the electric field across a magnetospheric gap at the base of the radio jet.

Phenotype of dendritic cells generated from peripheral blood monocytes of patients with ovarian cancer.

OBJECTIVES: The aim of our study was to generate dendritic cells (DCs) from peripheral blood monocytes (PBMC) of patients suffering from ovarian cancer. MATERIALS AND METHODS: Immature DCs were generated from PBMC cultured in RPMI 1640 medium with 2% human serum albumin (HSA), supplemented with recombinant human (rh) granulocyte macrophage colony stimulating factor (GM-CSF) and rh interleukin (IL)-4. After 5 days of culture, DC maturation was induced by the addition of an ovarian cancer cell line (CAOV3) lysate and after 6 days of rh tumor necrosis factor (TNF)-α for a further 2 days. The phenotype of the generated cells was assessed by flow cytometry for the expressions of human leukocyte antigen (HLA)-DR, costimulatory molecules (e.g., CD86, CD80), CD83, CD1a, and CD14. PBMC cultured in 2% HSA without rhIL-4, rhGM-CSF, rh-TNF-α, or tumor cell lysate formed the control group. RESULTS: The 2.41% (interquartile range, 1.51%-3.52%) of CD45+/CD14+ cells in cultures with rhIL-4, rhGM-CSF, rhTNF-α and tumor cell lysate was significantly lower than in the control group (31.10%; interquartile range, 11.11%-64.06%). Cultures with rhIL-4, rhGM-CSF, rhTNF-α, and tumor cell lysate showed a higher percentage (19.96%; interquartile range, 9.30%-24.42%) of fully mature CD83+/CD1a-/HLA-DR+ DCs compared with control culture (6.02%; interquartile range, 3.01%-7.37%). There was no significant difference in the expression of the immature DC marker (CD1a) between the cultures. The expression of co-stimulatory markers (CD80, CD86, HLA-DR) was greater (24.29%; interquartile range, 18.68%-33.95%) on DCs from cultures with rhIL-4, rhGM-CSF, TNF-α, and tumor cell lysate versus controls (4.93%; interquartile range, 2.67%-9.09%). CONCLUSION: Our data demonstrated that immature and mature DCs can be generated from adherent human PBMC from ovarian cancer patients cultured with rhIL-4, rhGM-CSF, rhTNF-α, and tumor cell lysates.

Observation of pulsed gamma-rays above 25 GeV from the Crab pulsar with MAGIC.

One fundamental question about pulsars concerns the mechanism of their pulsed electromagnetic emission. Measuring the high-end region of a pulsar's spectrum would shed light on this question. By developing a new electronic trigger, we lowered the threshold of the Major Atmospheric gamma-ray Imaging Cherenkov (MAGIC) telescope to 25 giga-electron volts. In this configuration, we detected pulsed gamma-rays from the Crab pulsar that were greater than 25 giga-electron volts, revealing a relatively high cutoff energy in the phase-averaged spectrum. This indicates that the emission occurs far out in the magnetosphere, hence excluding the polar-cap scenario as a possible explanation of our measurement. The high cutoff energy also challenges the slot-gap scenario.

Very-high-energy gamma rays from a distant quasar: how transparent is the universe?

The atmospheric Cherenkov gamma-ray telescope MAGIC, designed for a low-energy threshold, has detected very-high-energy gamma rays from a giant flare of the distant Quasi-Stellar Radio Source (in short: radio quasar) 3C 279, at a distance of more than 5 billion light-years (a redshift of 0.536). No quasar has been observed previously in very-high-energy gamma radiation, and this is also the most distant object detected emitting gamma rays above 50 gigaelectron volts. Because high-energy gamma rays may be stopped by interacting with the diffuse background light in the universe, the observations by MAGIC imply a low amount for such light, consistent with that known from galaxy counts.

Dendritic cell subsets in the peritoneal fluid and peripheral blood of women suffering from ovarian cancer.

BACKGROUND: Evaluation of immature myeloid and lymphoid dendritic cells (DCs) in the peritoneal fluid (PF) and peripheral blood (PB) mononuclears of women with ovarian carcinoma (n = 47) and benign ovarian tumors (n = 37). METHODS: Mononuclear cells were isolated from PF and PB, stained with monoclonal antibodies (mAbs) against DC antigens (anti-BDCA-1, anti-BDCA-2), and estimated using flow cytometry. RESULTS: The percentage of PF myeloid DC (MDC) in mononuclears was significantly lower in patients with ovarian cancer in comparison to the group of nonmalignant ovarian tumors (0.65% and 6.95%). The percentage of PF lymphoid DCs (LDCs) was higher in patients with ovarian cancer than in the reference group (0.64% and 0.09%). The percentage of PB MDCs and LDCs did not differ significantly between studied groups. In women suffering from ovarian cancer the percentage of both MDCs and LDCs was higher in the PF than in the PB. In the reference group the percentage of MDCs was higher but that of LDCs was lower in the PF than in the PB. In women with ovarian cancer, PF MDCs/LDCs ratio was lower in comparison to patients with serous cystadenoma. In PB the ratio of MDCs to LDCs did not differ significantly between studied groups. CONCLUSIONS: We concluded that MDCs population may be affected by the presence of malignant disease. LDC subsets may have influence on the local immune response in the PF of women with malignant tumors of the ovary. (c) 2008 Clinical Cytometry Society.

Variable very-high-energy gamma-ray emission from the microquasar LS I +61 303.

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and can be used to elucidate the physics of relativistic jets. We report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I 61 + 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, which suggests that the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or absorption processes.

[Difficulties in differential diagnosis of adnexal masses during pregnancy: the role of greyscale and color doppler sonography]. / Trudnosci diagnostyki róznicowej guzów przydatkowych w ciazy: rola ultrasonografu z kolorowym Dopplerem.

We have attempted to determine the accuracy of greyscale and color Doppler ultrasound in the differentiation of adnexal masses in pregnancy. The studied group included 2245 pregnant women from low risk population. Following criteria were evaluated: maximal diameter and volume of the tumor, echogenicity, presence of septa and papillary projections in grey scale sonography. Color Doppler analysis included blood vessel presence and arrangement and blood flow characteristics with the use of pulsatility (PI), resistive (RI) and systolic/diastolic (S/D) indices. Preoperative CA-125 serum levels were available in 11 patients. In 66 (2.94%) patients adnexal tumors were detected during routine ultrasound scan at the end of the first trimester. Twenty-seven masses (1.2%) persisted beyond 16 weeks of gestation and were subsequently surgically removed. Pathological diagnosis confirmed 19 serous cystadenomas, 4 endometriomas and 2 dermoids, one pedunculated myoma and one fibrothecoma. Mean size of the tumors was 79 Jmm (range: 43-245 mm), mean volume 166. lml (range: 30-1320 ml). Doppler indices values presented as mean, SD and range were as follows: PI = 1.26 +/- 0.71 (range: 0.57-3.84); RI = 0.61 +/- 0.15 (range: 0.33-0.89) and S/D = 2.62 +/- 0.98 (range: 1.17-4.91). Median serum concentration of CA-125 was 17 IU/ml (range: 8.4-1247 IU/ml). Only 3 of these women had elevated (> 35 IU/ml) levels: 2 endometriomas (344 IU/ml and 1247 IU/ml) and one myoma (37 IU/ml), respectively. Based on the sonographic findings two solid tumors were incorrectly classified as probably malignant (fibrothecoma and subserous myoma). Negative predictive value of ultrasound diagnosis in the studied population was therefore 92.6% (25 of 27). We conclude that although prenatal sonography has the potential to correctly classify most of adnexal masses, caution in risk assessment is needed especially when persistent solid tumor is found.

[The influence of hypoxia on the proliferation of endothelial cells originating from human umbilical vein (HUVEC)--an in vitro study]. / Wplyw niedotlenienia na proliferacje komórek sródblonka z naczyn pepowiny ludzkiej (HUVEC) in vitro.

In this study we took for culture the early-passage human umbilical vein endothelial cells during 12, 24 and 36 hours of hypoxia. To assess the relative contributions of hypoxia, we compared the rates of BrDU incorporation into DNA of proliferating endothelial cells under normoxix and hypoxic conditions. Significant differences in proliferation rates were found only between 24 hours hypoxic group and the control group. Our results support the hypothesis that increased proliferation of human umbilical vein endothelial cells may reflect an adaptation of fetoplacental circulation to hypoxic conditions.

[Color and power doppler ultrasonographic measurement of the uterine blood flow in subfertile women with unstimulated cycles]. / Ocena przeplywu naczyniowego wewnatrz i wokól blony sluzowej macicy kobiet z obnizona plodnoscia przy zastosowaniu sonoangiografii z kolorowym i "power" Dopplerem.

We have assessed the usefulness of color and power Doppler velocimetry in uterine and radial arteries in a group of subfertile women who were referred for infertility treatment. The study group comprised of 44 women monitored at 7-10th, 11-14th and 15-18th day of unstimulated cycle. The control group comprised of 14 women who were monitored for the intrauterine insemination due to male factor and who had normal pelvis on laparoscopy and ovulatory cycles. Following study groups were evaluated: 11 women with endometriosis, 10 women with tubal factor, 12 patients with anovulatory cycles and 11 women with unexplained infertility. We have found a significant increase in uterine artery PI in early luteal phase of the cycle in women with endometriosis, with tubal factor and with unexplained infertility. Elevated uterine artery PI was also found in women with anovulatory cycles between 7th and 10th day of the study. Using power Doppler sonography we were able to detect subendometrial blood flow in 92% of control women and in 75% to 91% of patients in other studied groups. Significant increase in radial artery PI was found between 15th and 18th day of cycle in women with unexplained infertility and with anovulatory cycles. The present results suggest that increased impedance to blood flow may be regarded as possible cause of infertility. Larger studies with comparison to conception rates are needed to validate clinically this hypothesis.

[Personal observations concerning surgical treatment of urinary stress incontinence in women]. / Wlasne spostrzezenia dotyczace operacyjnego leczenia wysilkowego nietrzymania moczu u kobiet.

Own observations concerning surgical treatment of urinary stress incontinence based upon the clinical follow-up of 82 treated women are presented. Depending on the method of surgical treatment, patients with urinary stress incontinence have been divided into 3 groups: I group-(42 women), where retropubic colpo-uretero-pexy has been performed following the rules previously suggested by Tanagho, Sprogis et al., with 92.8% of positive result, II group-(34 women), where Mieszczerski or Fothergill type of surgery has been performed, with 88.2% of positive results, and III group-(6 women), where vaginal vault has been suspended to the musculo-fascial flap, with positive results in all treated patients. The obtained results suggest that in every case of urinary stress incontinence the conservative approach should be the primary strategy of treatment. Analysis of the results revealed that retropubic colpo-uretero-pexy was an effective surgical method of urinary stress incontinence treatment in women with no cystocele and with proper uterine statics. In patients with correct uterine statics but with coexisting cystocoele, even of a minor grade, retropubical kolpouretropexy should be joined with the surgery from a vaginal access.

[Influence of betamethasone on the vascular resistance in human placenta perfused in vitro]. / Wplyw betametazonu na opór naczyniowy lozyska ludzkiego perfundowanego in vitro.

The study was carried out on 48 human placentas perfused in vitro. Betamethasone was administered into the arterial system in the following single doses: 0.4 mg, 2 mg, 10 mg. It was found that betamethasone decreases the pressure of perfusion in different ways depending on the dose. A statistically significant decrease in perfusion pressure was observed in 30th minute of the experiment after administering 2 mg while a dose of 10 mg induced a significant perfusion pressure in 30th and 60th minute of the experiment. The relaxation of the blood vessels of the placenta under the influence of betamethasone was attributed to the action of dopamine on the dopaminergic receptors of the vessels and glucocorticoids modifying this action. The results of the experiments point to a positive action of betamethasone on the blood vessels of human placenta.

[Energetic metabolism of the placenta and vascular blood flow as criteria for the choice of drugs in risk pregnancy--results of our investigations]. / Der energetische Metabolismus der Plazenta und der Gefässdurchfluss als Kriterien für die Wahl der Arzneimittel bei der Risikoschwangerschaft--Ergebnisse eigener Untersuchungen.

Object of this paper was to estimate the vascular resistances of the placenta and the lactate/pyruvate-quotient influenced by 8 and 40 mu/min orciprenaline and 320 micrograms/min papaverine. 38 placentas were tested in extraorganic circulation. The content of lactic acid and pyruvic acid was determined in the perfusion solution flowing out of the umbilical vein. Pressure was registered with cymograph. Infusion of 8 micrograms/min orciprenaline diminishes the lactate/pyruvate-quotient and the vascular resistances. 40 micrograms/min orciprenaline causes spasm of placental vessels in the terminal phase of examination. In this group the processes of oxygenation were limited by the oxygen content in the perfusion solution. Papaverine turned the metabolism of the placenta to an anaerob way and the antispasmodic effect was shortlasting.--Therefore the drug effect results out of a metabolic and a spasmolytic component. In risk pregnancy there has to be considered in addition to the spasmolytic the metabolic effects, too.