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Swift J1818.0−1607 is a radio-emitting magnetar that was discovered in X-ray outburst in March 2020. Starting four days after this outburst, we began a nearly five month multi-frequency observing campaign at 2.2, 8.4, and 32 GHz using telescopes in the NASA Deep Space Network. Using a dual-frequency observing mode, we were able to observe Swift J1818.0−1607 simultaneously at either 2.2 and 8.4 GHz or 8.4 and 32 GHz. Over the course of the campaign, we find that the flux density increases substantially and the spectrum changes from uncharacteristically steep (α < −2.2) to the essentially flat (α ≈ 0) spectrum typical of radio-emitting magnetars. In addition to the expected profile evolution on timescales of days to months, we find that Swift J1818.0−1607 also exhibits mode switching where the pulse profile changes between two distinct shapes on timescales of seconds to minutes. For two of the radio observations, we also had accompanying X-ray observations using the Neutron Star Interior Composition Explorer (NICER) telescope that occurred on the same day. We find a near anti-alignment (0.40 phase cycles) between the peaks of the radio and X-ray pulse profiles, which is most likely explained by an intrinsic misalignment between the X-ray and radio emitting regions.

The co-chaperone p50/Cdc37 is an important partner for Hsp90, assisting in molecular chaperone activities, particularly with regard to the regulation of protein kinases. Analysis of the structure of Hsp90-Cdc37-kinase complexes demonstrates the way in which Cdc37 interacts with and controls the folding of a large proportion of intracellular protein kinases. This co-chaperone thus stands at the hub of a multitude of intracellular signaling networks. Indeed, the influence of Cdc37 reaches beyond the housekeeping pathways of protein folding into the regulation of a wide range of cellular processes. This co-chaperone has attracted attention as a potential intermediate in carcinogenesis. Cdc37 is an attractive potential target in cancer due to (1) high expression in a number of tumor types and (2) control of multiple signaling pathways. These properties indicate (3) a potential for selectivity due to its elevated expression in malignant cells and (4) robustness, as the co-chaperone may control multiple growth signaling pathways and thus be less prone to evolution of resistance than less versatile oncoproteins. Cdc37 may also be involved in other aspects of pathophysiology and has been shown to be secreted in exosomes. Protein aggregation disorders have been linked to age-related declines in molecular chaperones and co-chaperones. Cdc37 also appears to be a potential agent in longevity due to its links to protein folding and autophagy, and it will be informative to study the role of Cdc37 maintenance/decline in aging organisms.

Epithelial-mesenchymal transition (EMT) is a reversible cellular program that transiently places epithelial (E) cells into pseudo-mesenchymal (M) cell states. The malignant progression and resistance of many types of carcinomas depends on EMT activation, partial EMT and hybrid E/M status in neoplastic cells. EMT is activated by tumor microenvironmental TGFβ signal and EMT-inducing transcription factors, such as ZEB1/2 in tumor cells. However, reverse EMT factors are less studied. We demonstrate that transcription factor SCAND1 can revert mesenchymal and hybrid E/M phenotype of cancer cells to a more epithelial, less invasive status and inhibit their proliferation and migration. SCAND1 is a SCAN domain-containing protein and hetero-oligomerizes with SCAN-zinc finger transcription factors, such as MZF1, for accessing DNA and transcriptional co-repression of target genes. We found that SCAND1-MZF1 co-expression and interaction correlated with maintaining epithelial features, whereas the simultaneous loss of SCAND1 and MZF1 correlated with mesenchymal features of tumor cells. Overexpression of SCAND1 over endogenous MZF1 in DU-145 prostate cancer cells reverted their hybrid E/M status into cobblestone morphology with increased epithelial adhesion by E-cadherin and β-catenin relocation. Consistently, co-expression analysis in TCGA PanCancer Atlas revealed that both SCAND1 and MZF1 co-express and are negatively correlated with EMT driver genes, including CTNNB1, ZEB1, ZEB2 and TGFBR, in prostate tumor specimens. In addition, SCAND1 overexpression suppressed tumor cell proliferation by reducing the MAP3K-MEK-ERK signaling pathway. Of note, SCAND1-overexpressing DU-145 cells migrated slower than control cells with decreased lymph node metastasis of prostate cancer in a mouse tumor xenograft model. Kaplan-Meyer analysis showed high expression of MZF1 and SCAND1 to correlate with better prognoses in pancreatic cancer and head and neck cancers, although with poorer prognosis in kidney cancer. Overall, these data suggest that the combination of SCAND1-MZF1 complexes may revert the EMT mechanism in cancer to establish an epithelial phenotype. These effects seem to include co-repression of EMT-driver genes and suppression of tumor cell proliferation via inhibition of the MAP3K-MEK-ERK signaling pathway.

Epithelial–mesenchymal transition (EMT) is a reversible cellular program that transiently places epithelial (E) cells into pseudo-mesenchymal (M) cell states. The malignant progression and resistance of many carcinomas depend on EMT activation, partial EMT, or hybrid E/M status in neoplastic cells. EMT is activated by tumor microenvironmental TGFβ signal and EMT-inducing transcription factors, such as ZEB1/2, in tumor cells. However, reverse EMT factors are less studied. We demonstrate that prostate epithelial transcription factor SCAND1 can reverse the cancer cell mesenchymal and hybrid E/M phenotypes to a more epithelial, less invasive status and inhibit their proliferation and migration in DU-145 prostate cancer cells. SCAND1 is a SCAN domain-containing protein and hetero-oligomerizes with SCAN-zinc finger transcription factors, such as MZF1, for accessing DNA and the transcriptional co-repression of target genes. We found that SCAND1 expression correlated with maintaining epithelial features, whereas the loss of SCAND1 was associated with mesenchymal phenotypes of tumor cells. SCAND1 and MZF1 were mutually inducible and coordinately included in chromatin with hetero-chromatin protein HP1γ. The overexpression of SCAND1 reversed hybrid E/M status into an epithelial phenotype with E-cadherin and β-catenin relocation. Consistently, the co-expression analysis in TCGA PanCancer Atlas revealed that SCAND1 and MZF1 expression was negatively correlated with EMT driver genes, including CTNNB1, ZEB1, ZEB2 and TGFBRs, in prostate adenocarcinoma specimens. In addition, SCAND1 overexpression suppressed tumor cell proliferation by reducing the MAP3K-MEK-ERK signaling pathway. Of note, in a mouse tumor xenograft model, SCAND1 overexpression significantly reduced Ki-67(+) and Vimentin(+) tumor cells and inhibited migration and lymph node metastasis of prostate cancer. Kaplan–Meier analysis showed high expression of SCAND1 and MZF1 to correlate with better prognoses in pancreatic cancer and head and neck cancers, although with poorer prognosis in kidney cancer. Overall, these data suggest that SCAND1 induces expression and coordinated heterochromatin-binding of MZF1 to reverse the hybrid E/M status into an epithelial phenotype and, inhibits tumor cell proliferation, migration, and metastasis, potentially by repressing the gene expression of EMT drivers and the MAP3K-MEK-ERK signaling pathway.

The current generation of all-sky surveys is rapidly expanding our ability to study variable and transient sources. These surveys, with a variety of sensitivities, cadences, and fields of view, probe many ranges of time-scale and magnitude. Data from the Zwicky Transient Facility (ZTF) yields an opportunity to find variables on time-scales from minutes to months. In this paper, we present the codebase, ztfperiodic, and the computational metrics employed for the catalogue based on ZTF’s Second Data Release. We describe the publicly available, graphical-process-unit optimized period-finding algorithms employed, and highlight the benefit of existing and future graphical-process-unit clusters. We show how generating metrics as input to catalogues of this scale is possible for future ZTF data releases. Further work will be needed for future data from the Vera C. Rubin Observatory’s Legacy Survey of Space and Time.

KRAS-G12C targeting inhibitors (G12Cis), such adagrasib and sotorasib, have shown specificity and promising anti-tumor potential in non-small cell lung carcinoma (NSCLC). However, acquired resistance to these inhibitors has recently been observed in the clinic. Mechanisms of resistance to G12Cis are associated with genetic alterations of several pro-growth signaling pathways. A strategy to overcome the multifarious resistance mechanisms to G12Cis that does not require further molecular characterization is needed. To develop an all-round strategy to overcome G12Ci resistance mechanisms, we exposed NCI-H358, NCI-H1373, and MIAPaCa2 cell lines harboring KRAS-G12C mutations to increasing concentrations of sotorasib or adagrasib over 6 months. The resulting resistant cells proliferate normally in the presence of 10 μM sotorasib or adagrasib. Sotorasib-resistant cells designated as NCI-H358S-R, NCI-H1373S-R, and MIAPaCa2S-R remarkably remain sensitive to adagrasib, suggesting but not proving that the resistant cells remain dependent on mutant KRAS for survival. Adagrasib-resistant cells designated as NCI-H358A-R, NCI-H1373A-R, and MIAPaCa2A-R in contrast remain resistant to both sotorasib and adagrasib. Treatment of adagrasib-resistant cells with 500 nM adagrasib attenuated KRAS activity, however, this was compensated by activation of varied receptor tyrosine kinases (RTKs) to restore phospho-ERK levels, a surrogate marker of RAS activity. Moreover, treatment of de novo resistant NSCLC cells lines NCI-H2030, NCI-H1792, and NCI-H23 or NSCLC patient derived organoids (PDOs) with 500 nM adagrasib resulted in sustained phospho-ERK levels through activation of RTKs. These results indicate the need to simultaneously reduce both KRAS G12C and compensating RTK activity to effectively treat NSCLC. The majority of oncogenic RTKs are dependent on the molecular chaperone HSP90 to maintain stability. Therefore, a heterobifunctional chaperone mediated protein (CHAMP) degrader, RNK07421, was designed to specifically target both KRAS G12C and HSP90. RNK07421 induces an artificial ternary complex between KRAS G12C and HSP90, while also inhibiting the activity of both proteins. The RNK07421 coordinated KRAS G12C-HSP90 interaction promotes the proteasome degradation of KRAS G12C likely via HSP90 associated E3-ligases. Treatment of adagrasib resistant NSCLC cells and PDOs with RNK07421 resulted in reduced levels of KRAS G12C and phospho-ERK along with resistance enabling RTKs: EGFR, BRAF and FGFR2. Furthermore, in vivo treatment of resistant NSCLC cells with RNK07421 demonstrated dramatic tumor reduction as compared to G12Ci. Together these observations indicate that the novel mechanisms of action of RNK07421 may provide several advantages to G12Cis and possibly other targeted protein degradation agents to effectively treat KRAS G12C dependent NSCLC. Citation Format: Ines Pulido, Jennifer M. Graeber, Brianna C. Borger, Kevin P. Foley, Weiwen Ying, Chenghao Ying, Jinhua Li, Yaya Wang, Yuetong Sun, Yan Dai, Guoqiang Wang, Thomas L. Prince, Takeshi Shimamura. Overcoming KRAS G12C inhibitor resistance with chaperone-mediated protein degrader in NSCLC [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr B026.

KRAS is the most frequently mutated oncogene in cancer and is particularly common in lung, pancreatic and colorectal cancers. While KRAS has been undruggable, covalent KRAS G12C inhibitors, sotorasib and adagrasib, that bind preferentially to GDP-bound KRAS and prevent exchange for GTP and interaction with downstream effectors, have been approved for use in NSCLC. While these reagents show promising efficacy and are well-tolerated by patients, acquired drug resistance rapidly develops. The drug resistance landscape of G12C inhibitors is complex, with several mechanisms of resistance already described, ranging from reactivation of mutated RAS or other RAS isoforms, acquisition of new KRAS mutations, and genetic alterations of pro-growth signaling pathways. Thus, an ideal approach to overcoming drug resistance will need to target multiple different mechanisms. We exposed NSCLC and pancreatic cell lines (NCI-H358, NCI-H1373 and MIA PaCa-2, respectively) to increasing doses of sotorasib or adagrasib until the resulting cells grow normally in the presence of 10 µM of each inhibitor. Sotorasib-resistant cells, designated as S-R, remarkably remain sensitive to adagrasib, suggesting that the resistant cells continue to be dependent on mutant KRAS for survival. In contrast, adagrasib-resistant cells, designated as A-R, are resistant to both inhibitors. Treatment of innate and acquired adagrasib-resistant cells with 500 nM adagrasib attenuated RAS activity; however, this is compensated for by increased KRAS, HRAS and NRAS mRNA and restored p-ERK levels, a surrogate marker of RAS activity. Moreover, analysis of RTK activation in drug-resistant cells reveals that adagrasib treatment induces the activity of specific RTKs in a cell-line specific manner. Interestingly, during the acquisition of adagrasib resistance, several RTKs are strongly induced to escape drug inhibition. These results indicate the need to simultaneously reduce both KRAS G12C and compensating RTK activity to effectively treat KRAS G12C NSCLC. The majority of oncogenic RTKs are known to be dependent on the molecular chaperone HSP90 for their proper folding and stability. Therefore, a heterobifunctional chaperone-mediated protein degrader (CHAMP), RNK07421, was designed to specifically target both KRAS G12C and HSP90. RNK07421 induces an artificial ternary complex with KRAS G12C and HSP90, while also inhibiting the activity of both proteins and promoting proteasomal degradation of KRAS G12C via HSP90-associated E3-ligases. Treatment of adagrasib-resistant NSCLC cells and PDOs with RNK07421 resulted in decreased levels of KRAS G12C, p-ERK and RTKs. Furthermore, in vivo treatment with RNK07421 demonstrated dramatic tumor growth inhibition as compared to adagrasib treatment alone. Together, these observations indicate that the novel mechanisms of action of RNK07421 may provide several advantages over G12C inhibitors and possibly other targeted protein degradation agents to effectively treat KRAS G12C-dependent NSCLC. Citation Format: Ines Pulido Endrino, Qiyue Luan, Jennifer Graeber, Brianna Borger, Chenghao Ying, Jinhua Li, Zimo Yang, Zhiyong Wang, Yaya Wang, Yuetong Sun, Yan Dai, Ian Papautsky, Thomas L. Prince, Guoqiang Wang, Kevin P. Foley, Weiwen Ying, Takeshi Shimamura. Overcoming KRAS G12C inhibitor resistance with a chaperone-mediated protein degrader (CHAMP) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB231.

Covalent KRAS(G12C) inhibitors have recently shown promising efficacy in the clinic. However, the rapid development of drug resistance compromises their long-term benefits, indicating the need for additional approaches to treat KRAS-mutated cancers. Targeted protein degradation represents one such potential approach. We have therefore explored applying Chaperone-mediated Protein Degradation (CHAMP) technology to degrade KRAS(G12C) protein. CHAMPs are heterobifunctional small molecules that mediate protein degradation by inducing proximity between a target protein and the HSP90 chaperone complex, resulting in target ubiquitination and degradation by the proteasome. Due HSP90 being highly activated in cancer cells, CHAMPs also preferentially accumulate in tumors relative to normal tissues, resulting in an improved therapeutic index relative to typical inhibitors. In order to chemically induce KRAS(G12C) degradation, CHAMP compounds were synthesized by covalently coupling KRAS(G12C)- and HSP90-binding moieties through a short linker. CHAMP treatment of KRAS(G12C)-mutated cell lines resulted in formation of a KRAS(G12C)-CHAMP-HSP90 ternary complex and subsequent proteasome-dependent KRAS(G12C) degradation and inhibition of cell proliferation. In contrast, combination treatment with KRAS(G12C) and HSP90 inhibitors did not result in substantial KRAS(G12C) degradation. Importantly, CHAMPs retained potency in cell line models of resistance to covalent KRAS(G12C) inhibitors. Further, in mouse xenograft models, CHAMPs displayed prolonged pharmacokinetics in tumors relative to plasma and normal tissues and strongly inhibited tumor growth at tolerated doses. Based on these findings, KRAS(G12C)-degrading CHAMPs represents a promising approach to the treatment of KRAS(G12C)-mutated cancers. Citation Format: Kevin P. Foley, Chenghao Ying, Yaya Wang, Yan Dai, Zhiyong Wang, Jinhua Li, Zimo Yang, Yuetong Sun, Hao Xin Zhou, Thomas L. Prince, Guoqiang Wang, Weiwen Ying. Chemically induced chaperone-mediated protein degradation (CHAMP) of KRAS(G12C) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1649.

Over a dozen millisecond pulsars are ablating low-mass companions in close binary systems. In the original "black widow", the 8-hour orbital period eclipsing pulsar PSR J1959+2048 (PSR B1957+20), high energy emission originating from the pulsar is irradiating and may eventually destroy a low-mass companion. These systems are not only physical laboratories that reveal the dramatic result of exposing a close companion star to the relativistic energy output of a pulsar, but are also believed to harbour some of the most massive neutron stars, allowing for robust tests of the neutron star equation of state. Here, we report observations of ZTF J1406+1222, a wide hierarchical triple hosting a 62-minute orbital period black widow candidate whose optical flux varies by a factor of more than 10. ZTF J1406+1222 pushes the boundaries of evolutionary models, falling below the 80 minute minimum orbital period of hydrogen-rich systems. The wide tertiary companion is a rare low metallicity cool subdwarf star, and the system has a Galactic halo orbit consistent with passing near the Galactic center, making it a probe of formation channels, neutron star kick physics, and binary evolution., 63 pages, 15 figures, 2 tables, published in Nature on May 4, 2022

Of more than a thousand known cataclysmic variables (CVs), where a white dwarf is accreting from a hydrogen-rich star, only a dozen have orbital periods below 75 minutes

There is a growing concern about an impact of low-Earth-orbit (LEO) satellite constellations on ground-based astronomical observations, in particular, on wide-field surveys in the optical and infrared. The Zwicky Transient Facility (ZTF), thanks to the large field of view of its camera, provides an ideal setup to study the effects of LEO megaconstellations - such as SpaceX's Starlink - on astronomical surveys. Here, we analyze the archival ZTF observations collected between 2019 November and 2021 September and find 5301 satellite streaks that can be attributed to Starlink satellites. We find that the number of affected images is increasing with time as SpaceX deploys more and more satellites. Twilight observations are particularly affected - a fraction of streaked images taken during twilight has increased from less than 0.5% in late 2019 to 18% in 2021 August. We estimate that once the size of the Starlink constellation reaches 10,000, essentially all ZTF images taken during twilight may be affected. However, despite the increase in satellite streaks observed during the analyzed period, the current science operations of ZTF are not yet strongly affected. We also find that redesigning Starlink satellites (by installing visors intended to block sunlight from reaching the satellite antennas to prevent reflection) reduces their brightness by a factor of 4.6 +/- 0.1 with respect to the original design in g, r, and i bands., Comment: accepted for publication in ApJ Letters, full table 1 included as ancillary file

Microlensing is a powerful technique to study the Galactic population of "dark" objects such as exoplanets both bound and unbound, brown dwarfs, low-luminosity stars, old white dwarfs, neutron stars, and almost the only way to study isolated stellar-mass black holes. The majority of previous efforts to search for gravitational microlensing events have concentrated towards high-density fields such as the Galactic bulge. Microlensing events in the Galactic plane have the advantage of closer proximity and better constrained relative proper motions, leading to better constrained lens mass estimates at the expense of a lower optical depth compared to events towards the Galactic bulge. We use the Zwicky Transient Facility (ZTF) Data Release 5 (DR5) compiled from 2018--2021 to survey the Galactic plane in the region of $|b| < 20^\circ$. We find a total of 60 candidate microlensing events including three that show a strong microlensing parallax effect. The rate of events traces Galactic structure, decreasing exponentially as a function Galactic longitude with scale length $\ell_0 \sim 37^\circ$. On average, we find Einstein timescales of our microlensing events to be about three times as long ($\sim60$ days) compared to those towards the Galactic bulge ($\sim20$ days). This pilot project demonstrates that microlensing towards the Galactic plane shows strong promise for characterization of dark objects within the Galatic disk., submitted to ApJ

We present the discovery of a new double detonation progenitor system consisting of a hot subdwarf B (sdB) binary with a white dwarf companion with an P=76.34179(2) min orbital period. Spectroscopic observations are consistent with an sdB star during helium core burning residing on the extreme horizontal branch. Chimera light curves are dominated by ellipsoidal deformation of the sdB star and a weak eclipse of the companion white dwarf. Combining spectroscopic and light curve fits we find a low mass sdB star, $M_{\rm sdB}=0.383\pm0.028$ M$_\odot$ with a massive white dwarf companion, $M_{\rm WD}=0.725\pm0.026$ M$_\odot$. From the eclipses we find a blackbody temperature for the white dwarf of 26,800 K resulting in a cooling age of $\approx$25 Myrs whereas our MESA model predicts an sdB age of $\approx$170 Myrs. We conclude that the sdB formed first through stable mass transfer followed by a common envelope which led to the formation of the white dwarf companion $\approx$25 Myrs ago. Using the MESA stellar evolutionary code we find that the sdB star will start mass transfer in $\approx$6 Myrs and in $\approx$60 Myrs the white dwarf will reach a total mass of $0.92$ M$_\odot$ with a thick helium layer of $0.17$ M$_\odot$. This will lead to a detonation that will likely destroy the white dwarf in a peculiar thermonuclear supernova. PTF1 2238+7430 is only the second confirmed candidate for a double detonation thermonuclear supernova. Using both systems we estimate that at least $\approx$1% of white dwarf thermonuclear supernovae originate from sdB+WD binaries with thick helium layers, consistent with the small number of observed peculiar thermonuclear explosions., accepted for publication in ApJL, 14 pages, 5 figures, 1 table

AT2019wey (SRGA J043520.9+552226, SRGE J043523.3+552234) is a transient first reported by the ATLAS optical survey in 2019 December. It rose to prominence upon detection, three months later, by the Spektrum-Roentgen-Gamma (SRG) mission in its first all-sky survey. X-ray observations reported in Yao et al. suggest that AT2019wey is a Galactic low-mass X-ray binary (LMXB) with a black hole (BH) or neutron star (NS) accretor. Here we present ultraviolet, optical, near-infrared, and radio observations of this object. We show that the companion is a short-period (P < 16 hr) low-mass (< 1 Msun) star. We consider AT2019wey to be a candidate BH system since its locations on the L_radio--L_X and L_opt--L_X diagrams are closer to BH binaries than NS binaries. We demonstrate that from 2020 June to August, despite the more than 10 times brightening at radio and X-ray wavelengths, the optical luminosity of AT2019wey only increased by 1.3--1.4 times. We interpret the UV/optical emission before the brightening as thermal emission from a truncated disk in a hot accretion flow and the UV/optical emission after the brightening as reprocessing of the X-ray emission in the outer accretion disk. AT2019wey demonstrates that combining current wide-field optical surveys and SRG provides a way to discover the emerging population of short-period BH LMXB systems with faint X-ray outbursts., Accepted by ApJ

White dwarfs represent the last stage of evolution of stars with mass less than about eight times that of the Sun and, like other stars, are often found in binaries. If the orbital period of the binary is short enough, energy losses from gravitational-wave radiation can shrink the orbit until the two white dwarfs come into contact and merge. Depending on the component masses, the merger can lead to a supernova of type Ia or result in a massive white dwarf. In the latter case, the white dwarf remnant is expected to be highly magnetised because of the strong magnetic dynamo that should arise during the merger, and be rapidly spinning from the conservation of the orbital angular momentum. Here we report observations of a white dwarf, ZTF J190132.9+145808.7, that exhibits these properties, but to an extreme: a rotation period of 6.94 minutes, a magnetic field ranging between 600 megagauss and 900 megagauss over its surface, and a stellar radius of about 2,100 km, slightly larger than the radius of the Moon. Such a small radius implies that the star's mass is close to the maximum white-dwarf mass, or Chandrasekhar mass. ZTF J190132.9+145808.7 is likely to be cooling through the Urca processes (neutrino emission from electron capture on sodium) because of the high densities reached in its core., Comment: 37 pages, 9 figures, published in Nature on June 30, 2021

Prostate cancer (PCa) screening using serum prostate-specific antigen (PSA) testing has caused unnecessary biopsies and overdiagnosis owing to its low accuracy and reliability. Therefore, there is an increased interest in identifying better PCa biomarkers. Studies showed that trained dogs can discriminate patients with PCa from unaffected men by sniffing urine. We hypothesized that urinary volatile organic compounds (VOCs) may be the source of that odor and could be used to develop urinary VOC PCa diagnosis models.Urine samples from 55 and 53 biopsy proven PCa-positive and -negative patients respectively were initially obtained for diagnostic model development. Urinary metabolites were analyzed by gas chromatography-mass spectrometry. A PCa diagnosis model was developed and validated using innovative statistical machine-learning techniques. A second set of samples (53 PCa-positive and 22 PCa-negative patients) were used to evaluate the previously developed PCa diagnosis model.The analysis resulted in 254 and 282 VOCs for their significant association (P .05) with either PCa-positive or -negative samples respectively. Regularized logistic regression analysis and the Firth method were then applied to predict PCa prevalence, resulting in a final model that contains 11 VOCs. Under cross-validation, the area under the receiver operating characteristic curve (AUC) for the final model was 0.92 (sensitivity, 0.96; specificity, 0.80). Further evaluation of the developed model using a testing cohort yielded an AUC of 0.86. As a comparison, the PSA-based diagnosis model only rendered an AUC of 0.54.The study describes the development of a urinary VOC-based model for PCa detection.

Two high-cadence surveys aiming for rotation period measurements of asteroids have been conducted in 2019 January and October using the Zwicky Transient Facility. From the surveys, 25 large superfast rotators (SFRs) were discovered and they are all main-belt asteroids (MBAs), except for one Mars crosser. These large SFRs have a diameter ranging from 0.43 to 7.87 km and a rotation period between 0.48 and 1.95 hr. Considering their diameters and fast rotations, they cannot be explained by rubble-pile structure unless using extraordinary high bulk densities. Cohesion, if available, can conserve these large SFRs. The estimated cohesion for these large SFRs could be up to thousands of pascals, much higher than the currently estimated cohesion for asteroids and that generated by the regolith of Moon and Mars. Such high-level cohesion can be produced from fine-grain regolith, like clay. However, the availability of such fine-grain regolith for asteroids is still unknown. Although the possibility of these large SFRs being large monolithic objects cannot be ruled out, this scenario is very unlikely given that the timescale of disruptive impact for MBAs in a similar diameter range is 107–108 yr.

We present the detection of a bright radio burst at radio frequencies between 2.2--2.3 GHz with the NASA Deep Space Network (DSN) 70 m dish (DSS-63) in Madrid, Spain from FRB~20200120E. This repeating fast radio burst (FRB) was recently discovered by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst (CHIME/FRB) instrument and reported to be associated with the M81 spiral galaxy at a distance of 3.6 Mpc. The high time resolution capabilities of the recording system used in this observation, together with the small amount of scattering and intrinsic brightness of the burst, allow us to explore the burst structure in unprecedented detail. We find that the burst has a duration of roughly 30 $\mu$s and is comprised of several narrow components with typical separations of 2--3 $\mu$s. The narrowest component has a width of $\lesssim$ 100 ns, which corresponds to a light travel time size as small as 30 m, the smallest associated with an FRB to date. The peak flux density of the narrowest burst component is 270 Jy. We estimate the total spectral luminosity of the narrowest component of the burst to be 4 $\times$ 10$^{\text{30}}$ erg s$^{\text{-1}}$ Hz$^{\text{-1}}$, which is a factor of $\sim$500 above the luminosities of the so-called "nanoshots" associated with giant pulses from the Crab pulsar. This spectral luminosity is also higher than that of the radio bursts detected from the Galactic magnetar SGR 1935+2154 during its outburst in April 2020, but it falls on the low-end of the currently measured luminosity distribution of extragalatic FRBs. These results provide further support for the presence of a continuum of FRB burst luminosities., Comment: Accepted

AM CVn systems are a rare type of accreting binary that consists of a white dwarf and a helium-rich, degenerate donor star. Using the Zwicky Transient Facility (ZTF), we searched for new AM CVn systems by focusing on blue, outbursting stars. We first selected outbursting stars using the ZTF alerts. We cross-matched the candidates with $Gaia$ and Pan-STARRS catalogs. The initial selection of candidates based on the $Gaia$ $BP$-$RP$ contains 1751 unknown objects. We used the Pan-STARRS $g$-$r$ and $r$-$i$ color in combination with the $Gaia$ color to identify 59 high-priority candidates. We obtained identification spectra of 35 sources, of which 18 are high priority candidates, and discovered 9 new AM CVn systems and one magnetic CV which shows only He-II lines. Using the outburst recurrence time, we estimate the orbital periods which are in the range of 29 to 50 minutes. We conclude that targeted followup of blue, outbursting sources is an efficient method to find new AM CVn systems, and we plan to followup all candidates we identified to systematically study the population of outbursting AM CVn systems., Submitted, comments and feedback welcome

Spectroscopic detection of narrow emission lines traces the presence of circumstellar mass distributions around massive stars exploding as core-collapse supernovae. Transient emission lines disappearing shortly after the supernova explosion suggest that the material spatial extent is compact and implies an increased mass loss shortly prior to explosion. Here, we present a systematic survey for such transient emission lines (Flash Spectroscopy) among Type II supernovae detected in the first year of the Zwicky Transient Facility survey. We find that at least six out of ten events for which a spectrum was obtained within two days of the estimated explosion time show evidence for such transient flash lines. Our measured flash event fraction (>30% at 95% confidence level) indicates that elevated mass loss is a common process occurring in massive stars that are about to explode as supernovae.

We present the goals, strategy and first results of the high-cadence Galactic plane survey using the Zwicky Transient Facility (ZTF). The goal of the survey is to unveil the Galactic population of short-period variable stars, including short period binaries and stellar pulsators with periods less than a few hours. Between June 2018 and January 2019, we observed 64 ZTF fields resulting in 2990 deg$^2$ of high stellar density in ZTF-$r$ band along the Galactic Plane. Each field was observed continuously for 1.5 to 6 hrs with a cadence of 40 sec. Most fields have between 200 and 400 observations obtained over 2-3 continuous nights. As part of this survey we extract a total of $\approx$230 million individual objects with at least 80 epochs obtained during the high-cadence Galactic Plane survey reaching an average depth of ZTF-$r$ $\approx$20.5 mag. For four selected fields with 2 million to 10 million individual objects per field we calculate different variability statistics and find that $\approx$1-2% of the objects are astrophysically variable over the observed period. We present a progress report on recent discoveries, including a new class of compact pulsators, the first members of a new class of Roche Lobe filling hot subdwarf binaries as well as new ultracompact double white dwarfs and flaring stars. Finally we present a sample of 12 new single-mode hot subdwarf B-star pulsators with pulsation amplitudes between ZTF-$r$ = 20-76 mmag and pulsation periods between $P$ = 5.8-16 min with a strong cluster of systems with periods $\approx$ 6 min. All of the data have now been released in either ZTF Data Release 3 or data release 4., Comment: accepted for publication in MNRAS, 16 pages, 10 figures and 5 tables

The Zwicky Transient Facility (ZTF) has been observing the entire northern sky since the start of 2018 down to a magnitude of 20.5 (5σ for 30 s exposure) in the g, r, and i filters. Over the course of two years, ZTF has obtained light curves of more than a billion sources, each with 50–1000 epochs per light curve in g and r, and fewer in i. To be able to use the information contained in the light curves of variable sources for new scientific discoveries, an efficient and flexible framework is needed to classify them. In this paper, we introduce the methods and infrastructure that will be used to classify all ZTF light curves. Our approach aims to be flexible and modular and allows the use of a dynamical classification scheme and labels, continuously evolving training sets, and the use of different machine-learning classifier types and architectures. With this setup, we are able to continuously update and improve the classification of ZTF light curves as new data become available, training samples are updated, and new classes need to be incorporated.

Using photometry collected with the Zwicky Transient Facility (ZTF), we are conducting an ongoing survey for binary systems with short orbital periods ($P_{\rm b}, 32 pages, 12 figures, 7 tables, submitted to ApJ

(Abridged) Using the Zwicky Transient Facility alert stream, we are conducting a large campaign to spectroscopically classify all transients occurring in galaxies in the Census of the Local Universe (CLU) catalog. The aim of the experiment is to construct a spectroscopically complete, volume-limited sample of transients coincident within 100" of CLU galaxies out to 200 Mpc, and to a depth of 20 mag. We describe the survey design and spectroscopic completeness from the first 16 months of operations. We present results from a systematic search for Calcium rich gap transients in the sample of 22 low luminosity (peak absolute magnitude $M > -17$), hydrogen poor events found in the experiment (out of 754 spectroscopically classified SNe). We report the detection of eight Calcium rich gap transients, and constrain their volumetric rate to be at least $\approx 15\pm5$% of the SN Ia rate. Combining this sample with ten events from the literature, we find a likely continuum of spectroscopic properties ranging from events with SN Ia-like features (Ca-Ia objects) to SN Ib/c-like features (Ca-Ib/c objects) at peak light. Within the Ca-Ib/c events, we find two populations of events distinguished by their red ($g - r \approx 1.5$ mag) or green ($g - r \approx 0.5$ mag) spectral colors at $r$-band peak, wherein redder events show strong line blanketing signatures, slower light curves, weaker He lines and lower [Ca II]/[O I] in the nebular phase. Together, we find that the spectroscopic continuum, volumetric rates and striking old environments are consistent with the explosive burning of He shells on low mass white dwarfs. We posit that Ca-Ia and red Ca-Ib/c objects are consistent with the double detonation of He shells with high He burning efficiency, while green Ca-Ib/c objects could arise from less efficient He burning scenarios such as detonations in low density He shells or He shell deflagrations., 30 figures, 6 tables. Submitted to ApJ

White dwarfs represent the last stage of evolution for low and intermediate-mass stars (below about 8 times the mass of our Sun), and like their stellar progenitors, they are often found in binaries. If the orbital period of the binary is short enough, energy losses from gravitational wave radiation can shrink the orbit until the two white dwarfs come into contact and merge. Depending on the masses of the coalescing white dwarfs, the merger can lead to a supernova of type Ia, or it can give birth to a massive white dwarf. In the latter case, the white dwarf remnant is expected to be highly magnetised due to the strong dynamo that may arise during the merger, and rapidly rotating due to conservation of the orbital angular momentum of the binary. Here we report the discovery of a white dwarf, ZTF J190132.9+145808.7, which presents all these properties, but to an extreme: a rotation period of 6.94 minutes, one of the shortest measured for an isolated white dwarf, a magnetic field ranging between 600 MG and 900 MG over its surface, one of the highest fields ever detected on a white dwarf, and a stellar radius of 1810 km, slightly larger than the radius of the Moon. Such a small radius implies the star's mass is the closest ever detected to the white dwarf maximum mass, or Chandrasekhar mass. In fact, as the white dwarf cools and its composition stratifies, it may become unstable and collapse due to electron capture, exploding into a thermonuclear supernova or collapsing into a neutron star. Neutron stars born in this fashion could account for 10% of their total population.