KMT-2016-BLG-1107: A New Hollywood-Planet Close/Wide Degeneracy

We show that microlensing event KMT-2016-BLG-1107 displays a new type of degeneracy between wide-binary and close-binary Hollywood events in which a giant-star source envelops the planetary caustic. The planetary anomaly takes the form of a smooth, two-day "bump" far out on the falling wing of the light curve, which can be interpreted either as the source completely enveloping a minor-image caustic due to a close companion with mass ratio $q=0.036$, or partially enveloping a major-image caustic due to a wide companion with $q=0.004$. The best estimates of the companion masses are both in the planetary regime ($3.3^{+3.5}_{-1.8}\,M_{\rm jup}$ and $0.090^{+0.096}_{-0.037}\,M_{\rm jup}$) but differ by an even larger factor than the mass ratios due to different inferred host masses. We show that the two solutions can be distinguished by high-resolution imaging at first light on next-generation ("30m") telescopes. We provide analytic guidance to understand the conditions under which this new type of degeneracy can appear.Comment: 23 pages, 7 figures, accepted for publication in A

A SEER database retrospective cohort of 547 patients with penile non-squamous cell carcinoma: demographics, clinical characteristics, and outcomes

IntroductionLittle research has investigated the prevalence and distribution of the diverse pathologies of non-squamous cell carcinoma (non-SCC) of the penis. Although rare in clinical practice, these cancers have become a focus of greater importance among patients, clinicians, and researchers, particularly in developing countries. The principal objective of this study was to analyze the major types of penile non-SCC, elucidate common treatment pathways, and highlight outcomes including 5-year survival.Materials/methodsThe Surveillance, Epidemiology, and End Results (SEER) database was queried between 2000 and 2018 to identify a retrospective cohort of patients with penile non-SCC. Demographic information, cancer characteristics, diagnostic methods, treatments administered, and survival were investigated.ResultsA total of 547 cases of penile non-SCC were included in the analysis. The most prevalent non-SCC cancers included epithelial neoplasms, not otherwise specified (NOS) (15.4%), unspecified neoplasms (15.2%), basal cell neoplasms (13.9%), blood vessel tumors (13.0%), nevi and melanomas (11.7%), and ductal and lobular neoplasms (9.9%). Over half (56.7%) of patients elected to undergo surgical intervention. Patients rarely received systemic therapy (3.8%) or radiation (4.0%). Five-year survival was 35.5%. Patients who underwent surgery had greater annual survival for 0–10 years compared to those who did not have surgery. Significant differences in survival were found between patients who had regional, localized, and distant metastases (p < 0.05). A significant difference in survival was found for patients married at diagnosis versus those who were unmarried at diagnosis (p < 0.05). Lower survival rates were observed for patients older than 70 years.DiscussionAlthough less prevalent than SCC, penile non-SCC encompasses a diverse set of neoplasms. Patients in this cohort had a high utilization of surgical management leading to superior outcomes compared to those not receiving surgery. Radiation is an uncommonly pursued treatment pathway. Patient demographics and socioeconomic variables such as marital status may be valuable when investigating cancer outcomes. This updated database analysis can help inform diagnosis, management, and clinical outcomes for this rare group of malignancies

KMT-2018-BLG-1990Lb: A Nearby Jovian Planet From A Low-Cadence Microlensing Field

We report the discovery and characterization of KMT-2018-BLG-1990Lb, a Jovian planet $(m_p=0.57_{-0.25}^{+0.79}\,M_J)$ orbiting a late M dwarf $(M=0.14_{-0.06}^{+0.20}\,M_\odot)$, at a distance (D_L=1.23_{-0.43}^{+1.06}\,\kpc), and projected at $2.6\pm 0.6$ times the snow line distance, i.e., a_{\rm snow}\equiv 2.7\,\au (M/M_\odot), This is the second Jovian planet discovered by KMTNet in its low cadence ($0.4\,{\rm hr}^{-1}$) fields, demonstrating that this population will be well characterized based on survey-only microlensing data.Comment: 24 pages, 7 figures, 4 table

Survival Is Worse in Patients Completing Immunotherapy Prior to SBRT/SRS Compared to Those Receiving It Concurrently or After

PURPOSE/OBJECTIVES: The abscopal effect could theoretically be potentiated when combined with immunomodulating drugs through increased antigen production. The optimal dosing and schedule of radiotherapy with immunotherapy are unknown, although they are actively investigated in laboratory and clinical models. Clinical data in patients treated for metastatic disease with both modalities may guide future studies. MATERIALS AND METHODS: This is a single-institution retrospective review of all patients treated with stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS) and immunomodulating therapy within 6 months before or after SBRT/SRS for metastatic cancer. Clinical and tumor characteristics were recorded, as well as SBRT/SRS details, immunotherapy details, and survival. Log-rank tests on Kaplan–Meier curves for overall survival (OS) that were calculated from the end of SBRT/SRS were used in univariate analysis and Cox proportional hazards regression for multivariate analysis. RESULTS: A total of 125 patients were identified who met the inclusion criteria; 70 received SBRT, and 57 received SRS. Eighty-three patients were treated for non-small cell lung cancer, 7 patients for small cell lung cancer, and 35 patients for other cancers, with the most common one being melanoma. Fifty-three percent of patients received nivolumab, 29% pembrolizumab, 13% atezolizumab, 5% other. Twenty percent received immunotherapy before SBRT/SRS, 39% during SBRT/SRS, 41% after. Eighty-six patients had died by the time of the analysis; the median OS for the whole cohort was 9.7 months. Patients who had completed immunotherapy prior to SBRT/SRS had worse OS than those who received concurrent therapy or immunotherapy after SBRT/SRS, with a difference in median OS of 3.6 months vs. 13.0 months (p = 0.010) that was retained on multivariate analysis (p = 0.011). There was no significant difference in OS between patients receiving SRS vs. SBRT (p = 0.20), sex (p = 0.53), age >62 years (p = 0.76), or lung primary vs. others (p = 0.73) on univariate or multivariate analysis. When comparing before/concurrent to after/concurrent administration, there is a difference in survival with after/concurrent survival of 8.181 months and before survival of 13.010 months, but this was not significant (p = 0.25). CONCLUSIONS: OS appears to be worse in patients who complete immunotherapy prior to SBRT/SRS compared to those receiving it concurrently or after. The design of this retrospective review may be prone to lead time bias, although the difference in median survival is longer than the 6-month window before SBRT/SRS and could only account for part of this difference. Further analysis into causes of death and toxicity and prospective studies are needed to confirm the results of this analysis

KMT-2018-BLG-1292: A Super-Jovian Microlens Planet in the Galactic Plane

We report the discovery of KMT-2018-BLG-1292Lb, a super-Jovian $M_{\rm planet} = 4.5\pm 1.3\,M_J$ planet orbiting an F or G dwarf $M_{\rm host} = 1.5\pm 0.4\,M_\odot$, which lies physically within {\cal O}(10\,\pc) of the Galactic plane. The source star is a heavily extincted $A_I\sim 5.2$ luminous giant that has the lowest Galactic latitude, $b=-0.28^\circ$, of any planetary microlensing event. The relatively blue blended light is almost certainly either the host or its binary companion, with the first explanation being substantially more likely. This blend dominates the light at $I$ band and completely dominates at $R$ and $V$ bands. Hence, the lens system can be probed by follow-up observations immediately, i.e., long before the lens system and the source separate due to their relative proper motion. The system is well characterized despite the low cadence $\Gamma=0.15$--$0.20\,{\rm hr^{-1}}$ of observations and short viewing windows near the end of the bulge season. This suggests that optical microlensing planet searches can be extended to the Galactic plane at relatively modest cost.Comment: 35 pages, 3 Tables, 8 figure

Structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.

Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific γ-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8 Å resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-γ-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and γ-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-γ-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site

OGLE-2018-BLG-0532Lb: Cold Neptune With Possible Jovian Sibling

We report the discovery of the planet OGLE-2018-BLG-0532Lb, with very obvious signatures in the light curve that lead to an estimate of the planet-host mass ratio $q=M_{\rm planet}/M_{\rm host}\simeq 1\times10^{-4}$. Although there are no obvious systematic residuals to this double-lens/single-source (2L1S) fit, we find that $\chi^2$ can be significantly improved by adding either a third lens (3L1S, $\Delta\chi^2=81$) or second source (2L2S, $\Delta\chi^2=65$) to the lens-source geometry. After thorough investigation, we conclude that we cannot decisively distinguish between these two scenarios and therefore focus on the robustly-detected planet. However, given the possible presence of a second planet, we investigate to what degree and with what probability such additional planets may affect seemingly single-planet light curves. Our best estimates for the properties of the lens star and the secure planet are: a host mass $M\sim 0.25\,M_\odot$, system distance $D_L\sim 1\,$kpc and planet mass $m_{p,1}= 8\,M_\oplus$ with projected separation $a_{1,\perp}=1.4\,$au. However, there is a relatively bright $I=18.6$ (and also relatively blue) star projected within $<50\,$mas of the lens, and if future high-resolution images show that this is coincident with the lens, then it is possible that it is the lens, in which case, the lens would be both more massive and more distant than the best-estimated values above.Comment: 48 pages, 9 figures, 7 table

Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation.

The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation