On 27 August 2016, the Juno spacecraft acquired science observations of Jupiter, passing less than 5000 kilometers above the equatorial cloud tops. Images of Jupiter's poles show a chaotic scene, ...unlike Saturn's poles. Microwave sounding reveals weather features at pressures deeper than 100 bars, dominated by an ammonia-rich, narrow low-latitude plume resembling a deeper, wider version of Earth's Hadley cell. Near-infrared mapping reveals the relative humidity within prominent downwelling regions. Juno's measured gravity field differs substantially from the last available estimate and is one order of magnitude more precise. This has implications for the distribution of heavy elements in the interior, including the existence and mass of Jupiter's core. The observed magnetic field exhibits smaller spatial variations than expected, indicative of a rich harmonic content.
On 29 September 2022 the Juno spacecraft flew within 354 km of Europa's surface while several instruments probed the moon's surroundings. During the close flyby, radio occultations were performed by ...collecting single‐frequency Doppler measurements. These investigations are essential to the study of Europa's ionosphere and represent the first repeat sampling of any set of conditions since the Galileo era. Ingress measurements resulted in a marginal detection with a peak ionospheric density of 4,000 ± 3,700 cm−3 (3σ) at 22 km altitude. A more significant detection emerged on egress, with a peak density of 6,000 ± 3,000 cm−3 (3σ) at 320 km altitude. Comparison with Galileo measurements reveals a consistent picture of Europa's ionosphere, and confirms its dependence on illumination conditions and position within Jupiter's magnetosphere. However, the overall lower densities measured by Juno suggest a dependence on time of observation, with implications for the structure of the neutral atmosphere.
Plain Language Summary
On 29 September 2022, NASA's Juno spacecraft flew very close to Jupiter's moon Europa. During the encounter, a radio occultation experiment was performed, where radio signals are exchanged between the spacecraft and ground stations as the former sets behind or rises from the moon as seen from the Earth. The scope of this experiment was studying the ionosphere of Europa, a layer of electrons and ions surrounding the moon. The Juno measurements confirmed the presence of the layer, with a structure similar to the one observed by the Galileo mission in the late 1990s.
Key Points
Europa's ionosphere was detected from Juno's X‐band Doppler data via NASA's Deep Space Network during a close encounter in 2022
Peak densities were 4,000 ± 3,700 cm−3 (3σ) at 22 km altitude during ingress and 6,000 ± 3,000 cm−3 (3σ) at 320 km during egress
The Juno ionospheric profiles are consistent with Galileo measurements, and show a dependence on solar zenith and magnetospheric ram angles
In June 2021, the Juno spacecraft executed a close flyby of Ganymede. During the encounter, Juno passed behind Ganymede for 15 min as observed from Earth, providing the geometry to conduct a radio ...occultation experiment to probe Ganymede's tenuous ionosphere. X‐band and Ka‐band radio links were transmitted from Juno to antennas at the Deep Space Network. Electrons encountered along the radio propagation path advance the signal's phase and a linear combination the two frequencies allows for a direct measurement of the electron content along the propagation path. On occultation ingress, an ionosphere peak of 2,000 ± 500 (1‐σ) cm−3 near the surface was observed. On occultation egress, no statistically significant ionosphere was detected. Ingress observation viewed where Ganymede's intrinsic magnetic field lines are open whereas egress observation viewed where the field lines are closed, implying electron impact ionization plays a key role in the generation of the ionosphere.
Plain Language Summary
Juno conducted a flyby of Ganymede, the largest Galilean moon of Jupiter, on 7 June 2021. During the flyby, the Juno spacecraft set behind Ganymede as observed by the Earth. Juno's radio signals were captured by the Deep Space Network during this time to make radio occultation measurements of Ganymede's ionosphere. Elevated electron density was measured on occultation ingress but no statistically significant ionosphere was detected on egress. These results are consistent with Galileo's radio occultation observations and provide insight into the generation mechanisms of Ganymede's ionosphere.
Key Points
A dual‐frequency radio occultation experiment of Ganymede's ionosphere was conducted with the Juno spacecraft on 7 June 2021
Ingress observed an ionosphere with peak density 2,000 ± 500 (1‐σ) cm−3 but no statistically significant signature was detected on egress
Ingress detection occurred in the open field line region, where higher electron impact ionization rates may increase the electron density
Ovarian cancer is the leading cause of mortality from gynecological malignancies, often undetectable in early stages. The difficulty of detecting the disease in its early stages and the propensity of ...ovarian cancer cells to develop resistance to known chemotherapeutic treatments dramatically decreases the 5-year survival rate. Chemotherapy with paclitaxel after surgery increases median survival only by 2 to 3 years in stage IV disease highlights the need for more effective drugs. The human immunodeficiency virus (HIV) infection is characterized by increased risk of several solid tumors due to its inherent nature of weakening of immune system. Recent observations point to a lower incidence of some cancers in patients treated with protease inhibitor (PI) cocktail treatment known as HAART (Highly Active Anti-Retroviral Therapy).
Here we show that ritonavir, a HIV protease inhibitor effectively induced cell cycle arrest and apoptosis in ovarian cell lines MDH-2774 and SKOV-3 in a dose dependent manner. Over a 3 day period with 20 muM ritonavir resulted in the cell death of over 60% for MDAH-2774 compared with 55% in case of SKOV-3 cell line. Ritonavir caused G1 cell cycle arrest of the ovarian cancer cells, mediated by down modulating levels of RB phosphorylation and depleting the G1 cyclins, cyclin-dependent kinase and increasing their inhibitors as determined by gene profile analysis. Interestingly, the treatment of ritonavir decreased the amount of phosphorylated AKT in a dose-dependent manner. Furthermore, inhibition of AKT by specific siRNA synergistically increased the efficacy of the ritonavir-induced apoptosis. These results indicate that the addition of the AKT inhibitor may increase the therapeutic efficacy of ritonavir.
Our results demonstrate a potential use of ritonavir for ovarian cancer with additive effects in conjunction with conventional chemotherapeutic regimens. Since ritonavir is clinically approved for human use for HIV, drug repositioning for ovarian cancer could accelerate the process of traditional drug development. This would reduce risks, limit the costs and decrease the time needed to bring the drug from bench to bedside.
Abstract Background Opportunities exist to revise the current residency selection process to capture desirable candidate competencies. We examined the extent to which components of the American ...College of Surgeons/Association for Surgical Education simulation-based medical student curriculum combined with a teamwork activity could be used as potential screening method. Methods Students participated in a workshop consisting of training/evaluation of knot tying, suturing, airway management, gowning/gloving, and teamwork. Surveys were given to students (MS) and faculty observers (FRS) to examine their opinions about the residency screening process, the most critical competencies to assess, and the effectiveness of each station for candidate evaluation. Results Communication (FRS 4.86±.35;MS 4.93±.26) leadership (FRS 4.41±.80;MS 4.5±.76), judgment (FRS 4.62 ±.74;MS 4.67±.62), professionalism (FRS 4.64 ±.73;MS 5.00±.00), integrity (FRS 4.71±.78;MS 4.87±.35), and grit/resilience (FRS 4.71±.78; MS 4.53±.74) were considered most valuable for candidate screening. The simulation-based curriculum for evaluation of residency candidates were rated lowest by both groups. Open response comments indicated positive perceptions of this process. Conclusions Employing simulation to assess candidates may be most beneficial for examining non-technical attributes. Future work should continue to explore this area.
Parathyroid carcinoma (PC) is rare and often diagnosed incidentally after local resection (LR) for other indications. Although recommended treatment has traditionally been radical surgery (RS), more ...recent guidelines suggest that LR alone may be adequate. We sought to further investigate outcomes of RS versus LR for localized PC.
PC patients from 2004 to 2015 with localized disease were identified from the National Cancer Database, then stratified by surgical therapy: LR or RS. Demographic and clinicopathologic data were compared. Cox proportional hazard models were constructed to estimate associations of variables with overall survival (OS). OS was estimated from time of diagnosis using Kaplan-Meier curves.
A total of 555 patients were included (LR = 522, RS = 33). The groups were comparable aside from LR patients having higher rates of unknown nodal status (66.9% versus 39.4%; p = 0.003). By multivariable analysis, RS did not have a significant association with OS (hazard ratio (HR) = 0.43, 95% confidence interval (95%CI) = 0.10, 1.83; p = 0.255), nor did positive nodal status (HR = 0.66, 95%CI = 0.09, 5.03; p = 0.692) and unknown nodal status (HR = 1.30, 95%CI = 0.78, 2.17; p = 0.311). There was no difference in OS between the LR and RS groups, with median survival not reached by either group at 10 years (median follow-up = 60.4 months; p = 0.20).
There was no difference in OS between LR and RS for localized PC. RS and nodal status may not impact survival as previously identified, and LR should remain a valid initial surgical approach. Future higher-powered studies are necessary to assess the effects of surgical approaches on morbidity and oncologic outcomes.
The aims of this study were to investigate telomere function in normal and Barrett's esophageal adenocarcinoma (BEAC) cells purified by laser capture microdissection and to evaluate the effect of ...telomerase inhibition in cancer cells in vitro and in vivo.
Epithelial cells were purified from surgically resected esophagi. Telomerase activity was measured by modified telomeric repeat amplification protocol and telomere length was determined by real-time PCR assay. To evaluate the effect of telomerase inhibition, adenocarcinoma cell lines were continuously treated with a specific telomerase inhibitor (GRN163L) and live cell number was determined weekly. Apoptosis was evaluated by Annexin labeling and senescence by beta-galactosidase staining. For in vivo studies, severe combined immunodeficient mice were s.c. inoculated with adenocarcinoma cells and following appearance of palpable tumors, injected i.p. with saline or GRN163L.
Telomerase activity was significantly elevated whereas telomeres were shorter in BEAC cells relative to normal esophageal epithelial cells. The treatment of adenocarcinoma cells with telomerase inhibitor, GRN163L, led to loss of telomerase activity, reduction in telomere length, and growth arrest through induction of both the senescence and apoptosis. GRN163L-induced cell death could also be expedited by addition of the chemotherapeutic agents doxorubicin and ritonavir. Finally, the treatment with GRN163L led to a significant reduction in tumor volume in a subcutaneous tumor model.
We show that telomerase activity is significantly elevated whereas telomeres are shorter in BEAC and suppression of telomerase inhibits proliferation of adenocarcinoma cells both in vitro and in vivo.
MicroRNA-101 (miR-101) expression is negatively associated with tumor growth and proliferation in several solid epithelial cancers. Enhancer of zeste homolog 2 (EzH2) appears to be a functional ...target of miR-101. We explore the role of miR-101 and its interaction with EzH2 in epithelial ovarian carcinoma (EOC).
In situ hybridization (ISH) for miR-101 was performed on EOC patient tissues and normal controls. EOC cell lines were transfected with miR-101 and subjected to growth analysis and clonogenic assays. Cell motility was assessed by Boyden chamber and wound-healing assays. P21(waf1/cip1) and EzH2 interaction was assessed by Chromatin Immunoprecipitation (ChIP) assay in MDAH-2774 cells. SCID mice were assessed for tumor burden after injection with miR-101 or control vector-treated MDAH-2774 cells.
ISH analysis revealed a decrease in miR-101 expression in EOC compared with normal tissue. MiR-101 re-expression in EOC cell lines resulted in increased apoptosis, decreased cellular proliferation, invasiveness, and reduced growth of tumor xenografts. CHIP assays revealed that re-expression of miR-101 inhibited the interaction of EzH2 with p21(waf1/cip1) promoter.
MiR-101 re-expression appears to have antitumor effects, providing a better understanding of the role of miR-101 in EOC.
Abstract Background Pericytes (PCs) have a synergistic relationship with endothelial cells (MVEC) in regulating capillary permeability. PCs express Toll-like receptor-4 (TLR-4). We hypothesize one ...mechanism of MVEC/PC co-culture permeability is regulated through lipopolysaccharide (LPS) activation of pericyte TLR-4. Methods Rat PCs were harvested and cultured. PCs were transfected with siRNA targeted to TLR-4. Western blotting was used to confirm gene silencing of TLR-4. A previously described co-culture permeability assay was performed after LPS treatment. Results Western blot confirmed successful silencing of TLR-4 in PCs, which was sustained for 7 days. A dose- and time-dependent effect of LPS on albumin clearance was seen in MVEC/PC co-cultures. Co-cultures with TLR-4 silenced in PCs eliminated the LPS dose-dependent increase in albumin clearance. Conclusions TLR-4 regulates pericyte mediated capillary leak seen with LPS exposure. Our TLR-4 silencing model can be used to further investigate TLR-4’s role in pericyte mediated capillary leak.
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