Resonant instabilities mediated by drag and electrostatic interactions in laboratory and astrophysical dusty plasmas

Dusty plasmas are known to support a diverse range of instabilities, including both generalizations of standard plasma instabilities and ones caused by effects specific to dusty systems. It has been recently demonstrated that a novel broad class of streaming instabilities, termed resonant drag instabilities (RDIs), can be attributed to a particular resonance phenomenon caused by defective eigenvalues of the linearized dust/fluid system. In this work, it is demonstrated that this resonance phenomenon is not unique to RDIs and can be used as a framework to understand a wider range of instabilities, termed resonant instabilities. Particular attention is given to the filamentary ionization instability seen in laboratory dusty plasmas and to the two-stream instability. It is shown that, due to the commonalities in underlying physics between the dust-ion-acoustic two-stream instability and the acoustic RDI, these instabilities should be relevant in strongly overlapping regimes in astrophysical dusty plasmas. It is proposed that a similar overlap in the experimental accessibility of these modes (and of the filamentary instability) allows for the possibility of experimental investigation of complex and astrophysically relevant instability dynamics.Comment: 18 pages, 15 figure

EUV Debris Mitigation using Magnetic Nulls

Next generation EUV sources for photolithography use light produced by laser-produced plasmas (LPP) from ablated tin droplets. A major challenge for extending the lifetime of these devices is mitigating damage caused by deposition of tin debris on the sensitive collection mirror. Especially difficult to stop are high energy (up to 10 keV) highly charged tin ions created in the plasma. Existing solutions include the use of stopping gas, electric fields, and magnetic fields. One common configuration consists of a magnetic field perpendicular to the EUV emission direction, but such a system can result in ion populations that are trapped rather than removed. We investigate a previously unconsidered mitigation geometry consisting of a magnetic null by performing full-orbit integration of the ion trajectories in an EUV system with realistic dimensions, and optimize the coil locations for the null configuration. The magnetic null prevents a fraction of ions from hitting the mirror comparable to that of the perpendicular field, but does not trap any ions due to the chaotic nature of ion trajectories that pass close to the null. This technology can potentially improve LPP-based EUV photolithography system efficiency and lifetime, and may allow for a different, more efficient formulation of buffer gas

α-Synuclein Expression Selectively Affects Tumorigenesis in Mice Modeling Parkinson's Disease

Alpha Synuclein (α-Syn) is a protein implicated in mechanisms of neuronal degeneration in Parkinson's disease (PD). α-Syn is primarily a neuronal protein, however, its expression is found in various tumors including ovarian, colorectal and melanoma tumors. It has been hypothesized that neurodegeneration may share common mechanisms with oncogenesis. We tested whether α-Syn expression affects tumorigenesis of three types of tumors. Specifically, B16 melanoma, E0771 mammary gland adenocarcinoma and D122 Lewis lung carcinoma. For this aim, we utilized transgenic mice expression the human A53T α-Syn form. We found that the in vivo growth of B16 and E0771 but not D122 was enhanced in the A53T α-Syn mice. The effect on tumorigenesis was not detected in age-matched APP/PS1 mice, modeling Alzheimer's disease (AD), suggesting a specific effect for α-Syn- dependent neurodegeneration. Importantly, transgenic α-Syn expression was detected within the three tumor types. We further show uptake of exogenously added, purified α-Syn, by the cultured tumor cells. In accord, with the affected tumorigenesis in the young A53T α-Syn mice, over- expression of α-Syn in cultured B16 and E0771 cells enhanced proliferation, however, had no effect on the proliferation of D122 cells. Based on these results, we suggest that certain forms of α-Syn may selectively accelerate cellular mechanisms leading to cancer

Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling

Obesity is a global epidemic causing morbidity and impaired quality of life. The melanocortin receptor 4 (MC4R) is at the crux of appetite, energy homeostasis, and body-weight control in the central nervous system and is a prime target for anti-obesity drugs. Here, we present the cryo-EM structure of the human MC4R-Gs signaling complex bound to the agonist setmelanotide, a cyclic peptide recently approved for the treatment of obesity. The work reveals the mechanism of MC4R activation, highlighting a molecular switch that initiates satiation signaling. In addition, our findings indicate that Ca2+ is required for agonist but not antagonist efficacy. These results fill a gap in understanding MC4R activation and could guide the design of future weight management drugs

Development and validation of novel algorithms to identify patients with inflammatory bowel diseases in Israel: an epi-IIRN group study

Mira Y Friedman,1,2 Maya Leventer-Roberts,3 Joseph Rosenblum,4 Nir Zigman,4 Iris Goren,4 Vered Mourad,4 Natan Lederman,5 Nurit Cohen,5 Eran Matz,6 Doron Z Dushnitzky,6 Nirit Borovsky,6 Moshe B Hoshen,3 Gili Focht,1 Malka Avitzour,1 Yael Shachar,1 Yehuda Chowers,7 Rami Eliakim,8 Shomron Ben-Horin,8 Shmuel Odes,9 Doron Schwartz,9 Iris Dotan,10 Eran Israeli,11 Zohar Levi,10 Eric I Benchimol,12–14 Ran D Balicer,3 Dan Turner1 On behalf of the Israeli IBD Research Nucleus (IIRN) 1The Juliet Keidan Institute of Pediatric Gastroenterology and Nutrition, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel; 2Braun School of Public and Community Medicine, The Hebrew University – Hadassah Medical Center, Jerusalem, Israel; 3Clalit Research Institute, Chief’s Office, Clalit Health Services, Tel Aviv, Israel; 4Maccabi Healthcare Services, Tel Aviv, Israel; 5Meuhedet Health Services, Tel Aviv, Israel; 6Leumit Health Services, Tel Aviv, Israel; 7Department of Gastroenterology, Rambam Health Care Campus, Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel; 8Department of Gastroenterology, Chaim Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; 9Department of Gastroenterology and Hepatology, Soroka Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel; 10Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel; 11Institute of Gastroenterology and Liver Diseases, Hadassah Medical Center, Hebrew University, Jerusalem, Israel; 12CHEO Inflammatory Bowel Disease Centre, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada; 13Department of Pediatrics and School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada; 14Institute for Clinical Evaluative Sciences, Ottawa, ON, Canada Background: Before embarking on administrative research, validated case ascertainment algorithms must be developed. We aimed at developing algorithms for identifying inflammatory bowel disease (IBD) patients, date of disease onset, and IBD type (Crohn’s disease [CD] vs ulcerative colitis [UC]) in the databases of the four Israeli Health Maintenance Organizations (HMOs) covering 98% of the population. Methods: Algorithms were developed on 5,131 IBD patients and 2,072 controls, following independent chart review (60% CD and 39% UC). We reviewed 942 different combinations of clinical parameters aided by mathematical modeling. The algorithms were validated on an independent cohort of 160,000 random subjects. Results: The combination of the following variables achieved the highest diagnostic accuracy: IBD-related codes, alone if more than five to six codes or combined with purchases of IBD-related medications (at least three purchases or ≥3 months from the first to last purchase) (sensitivity 89%, specificity 99%, positive predictive value [PPV] 92%, negative predictive value [NPV] 99%). A look-back period of 2–5 years (depending on the HMO) without IBD-related codes or medications best determined the date of diagnosis (sensitivity 83%, specificity 68%, PPV 82%, NPV 70%). IBD type was determined by the majority of CD/UC codes of the three recent contacts or the most recent when less than three contacts were recorded (sensitivity 92%, specificity 97%, PPV 97%, NPV 92%). Applying these algorithms, a total of 38,291 IBD patients were residing in Israel, corresponding to a prevalence rate of 459/100,000 (0.46%). Conclusion: The application of the validated algorithms to Israel’s administrative databases will now create a large and accurate ongoing population-based cohort of IBD patients for future administrative studies. Keywords: inflammatory bowel diseases, Crohn’s disease, ulcerative colitis, search algorithms, validation, case ascertainment, Israel, administrative database researc