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We report a new test of modified gravity theories using the large-scale structure of the Universe. This paper is the first attempt to (1) apply a joint analysis of the anisotropic components of galaxy two- and three-point correlation functions (2 and 3PCFs) to actual galaxy data and (2) constrain the nonlinear effects of degenerate higher-order scalar-tensor (DHOST) theories on cosmological scales. Applying this analysis to the Baryon Oscillation Spectroscopic Survey (BOSS) data release 12, we obtain the lower bounds of $-1.655 < \xi_{\rm t}$ and $-0.504 < \xi_{\rm s}$ at the $95\%$ confidence level on the parameters characterising the time evolution of the tidal and shift terms of the second-order velocity field. These constraints are consistent with GR predictions of $\xi_{\rm t}=15/1144$ and $\xi_{\rm s}=0$. Moreover, they represent a $35$-fold and $20$-fold improvement, respectively, over the joint analysis with only the isotropic 3PCF. We ensure the validity of our results by investigating various quantities, including theoretical models of the 3PCF, window function corrections, cumulative ${\rm S/N}$, Fisher matrices, and statistical scattering effects of mock simulation data. We also find statistically significant discrepancies between the BOSS data and the Patchy mocks for the 3PCF measurement. Finally, we package all of our 3PCF analysis codes under the name \textsc{HITOMI} and make them publicly available so that readers can reproduce all the results of this paper and easily apply them to ongoing future galaxy surveys., Comment: 60 pages, 21 figures, 22 tables; a set of codes for data analysis is publicly available at https://github.com/naonori/hitomi.git

Escherichia albertii is an emerging zoonotic foodborne pathogen. Several outbreaks of E. albertii have occurred particularly in Japan. Although birds have been considered as one of the most important reservoirs of this bacterium, information regarding the prevalence in birds is still scanty. We performed a survey of E. albertii in wild birds in Japan, and examined characteristics of the isolates. E. albertii specific gene was detected in 5 cloacal swabs out of 156 birds by PCR. Four E. albertii were isolated from a swallow with 2 different E. albertii strains and 2 pigeons in a flock by XRM-MacConkey agar. These isolates were assigned to biogroup 3, shown no resistance to any antimicrobials tested, and classified into 2 EAO-genotypes (EAOg2 and EAOg33) and untypable. Similar to clinical E. albertii strains, these isolates carried virulence genes including eae (n=4), paa (n=4), Eccdt-I (n=2) and stx2f (n=1) in addition to Eacdt. Interestingly, stx2f genes in a strain were located on an inducible bacteriophage, which can confer the ability to produce Stx2f to E. coli. In conclusion, Japanese wild birds carried E. albertii at the similar levels to the reported prevalence in birds. These isolates may have a potential to cause gastroenteritis in humans.

Purpose In contrast-enhanced abdominopelvic CT (CE-APCT) for oncologic follow-up, ultrahigh-resolution CT (UHRCT) may improve depiction of fine lesions and low-dose scans are desirable for minimizing the potential adverse effects by ionizing radiation. We compared image quality and radiologists’ acceptance of model-based iterative (MBIR) and deep learning (DLR) reconstructions of low-dose CE-APCT by UHRCT. Methods Using our high-resolution (matrix size: 1024) and low-dose (tube voltage 100 kV; noise index: 20–40 HU) protocol, we scanned phantoms to compare the modulation transfer function and noise power spectrum between MBIR and DLR and assessed findings in 36 consecutive patients who underwent CE-APCT (noise index: 35 HU; mean CTDIvol: 4.2 ± 1.6 mGy) by UHRCT. We used paired t-test to compare objective noise and contrast-to-noise ratio (CNR) and Wilcoxon signed-rank test to compare radiologists’ subjective acceptance regarding noise, image texture and appearance, and diagnostic confidence between MBIR and DLR using our routine protocol (matrix size: 512; tube voltage: 120 kV; noise index: 15 HU) for reference. Results Phantom studies demonstrated higher spatial resolution and lower low-frequency noise by DLR than MBIR at equal doses. Clinical studies indicated significantly worse objective noise, CNR, and subjective noise by DLR than MBIR, but other subjective characteristics were better (P Conclusion Image quality, except regarding noise characteristics, and acceptance by radiologists were better by DLR than MBIR in low-dose CE-APCT by UHRCT. Graphical abstract

We present a root-cause analysis of severe lost circulation and creation of its risk map in an offshore oil field, Abu Dhabi. Lost circulation of more than 100 barrel per hour (BPH) has occurred in sixteen (16) boreholes through the carbonate reservoir. Four (4) out of them experienced total loss. The authors investigated spatial distribution of lost circulation and allowable maximum overbalance based on review of drilling operation in nearly two hundred (200) boreholes. The critical overbalance to reactivate the natural fractures for the tensile-opening or shear-slip failures was analyzed by using geomechanical model. The present study clarified that most of severe lost circulations occurred at the specific sub-layers of the reservoir. The core observation showed that lost circulation occurred in the intervals in which fragmented rocks (rubbles) and fractures were distributed together. The fracture stability analysis revealed that the conductive fractures interpreted by borehole imager were geomechanically stable under conventional overbalance applied in drilling through the reservoir sections. Namely, the planer fractures were geomechanically stable under the current in-situ stress condition. The study concluded that the predominant root-cause of severe lost circulations in the carbonate reservoir was cave-related rocks (cave facies) and excessive overbalance applied to reservoir pressure. The cave facies were supposed to be formed by flank-margin cave system and its collapse due to deposition of overburden formations. A risk map of lost circulation defined the five areas with its potential risk. The risk map indicated not only the risk level of lost circulation but also practical recommendations on the depth to set casing and allowable maximum overbalance. It functions as a practical guide for the design of boreholes in the ongoing drilling campaign.

Dihydromaniwamycin E (

A rare actinomycetal strain of the genus Actinomycetospora was found to produce a new tryptophan derivative, designated mycetoindole (1). The structure of 1 was determined to be N-3-methylcrotonoyl (Z)-dehydrotryptophan by NMR and MS analytical methods. Compound 1 reduced the root growth of lettuce Lactuca sativa seedlings at concentrations above 0.1 μM and almost completely inhibited seed germination at 10 μM.

Three new tetronate-class polyketides, nomimicins B, C, and D, along with nomimicin, hereafter named nomimicin A, were isolated from the culture extract of Actinomadura sp. AKA43 collected from floating particles in the deep-sea water of Sagami Bay, Japan. The structures of nomimicins B, C, and D were elucidated through the interpretation of NMR and MS analytical data, and the absolute configuration was determined by combination of NOESY/ROESY and ECD analyses. Nomimicins B, C, and D showed antimicrobial activity against Gram-positive bacteria, Kocuria rhizophila and Bacillus subtilis, with MIC values in the range of 6.5 to 12.5 μg/mL. Nomimicins B and C also displayed cytotoxicity against P388 murine leukemia cells with IC50 values of 33 and 89 μM, respectively.

Prostate cancer (PC) is a leading cause of cancer-related death in men in Western countries. Androgen receptor (AR) signaling is a major driver of PC; therefore, androgen deprivation by medical and surgical castration is the standard treatment for patients with PC. However, over time, most patients will progress to metastatic castration-resistant PC. Enzalutamide is the only AR antagonist approved by the Food and Drug Administration for the treatment of metastatic castration-resistant PC. However, resistance to enzalutamide also develops in most patients with castration-resistant PC. Thus, there is an urgent need to develop new AR antagonists with new structures. For this purpose, we conducted both in silico and natural product screenings. From the in silico screening, we obtained T5853872 and more potent compound, STK765173. From the natural product screening, the novel compound arabilin was isolated from Streptomyces sp. MK756-CF1. Unlike STK765173, arabilin could overcome resistance to enzalutamide. Furthermore, we also extracted a novel compound, antarlide A, and its geometric isomers from Streptomyces sp. BB47. Antarlides A-F have novel 22-membered-ring macrocyclic structures, while antarlides G and H have 20-membered-ring structures. Both antarlides B and G showed potent AR antagonist activity in prostate cancer cells and could overcome resistance to enzalutamide.

WW domain-containing transcription regulator 1 (WWTR1) is one of the primary effectors in the Hippo pathway, which plays essential roles in cell differentiation into trophectoderm (TE) and inner cell mass cell lineages at the blastocyst stage. However, little is known about the roles of WWTR1 in preimplantation development. The present study aimed to explore the significance of WWTR1 expression in preimplantation development using an mRNA knockdown (KD) system in bovine embryos. We first quantitated WWTR1 expression at protein and mRNA levels from fertilization to blastocyst stage. WWTR1 proteins gradually shifted from extranuclear localization during the 16-cell stage to nuclear localization by morula stage. WWTR1 mRNA expression was also transiently upregulated at the 16-cell stage. WWTR1 KD efficiently repressed WWTR1 expression at protein and mRNA levels. The WWTR1 KD embryos developed to the blastocyst stage at rates equivalent to those of controls, but TE cell numbers were significantly decreased. Representative TE-expressed genes, including CDX2 and IFNT were also significantly decreased in WWTR1 KD blastocysts. These results provide the first demonstration that WWTR1 expression is responsible for normal TE cell development in preimplantation embryos. (c) 2021 Elsevier Inc. All rights reserved.

The thermotolerant strain Streptomyces sp. HR41 was found to produce compound 1 only in a 45 °C culture, and not at the standard temperature. We previously designated this type of compound as a "heat shock metabolite" (HSM). NMR and MS analytical techniques were used to determine that the chemical structure of 1 comprised a methylated-oxazole ring and a linear chain moiety modified with a terminal amide group. Thus, 1 was shown to be a new curromycin analog, which we have designated noaoxazole (1). Compound 1 weakly activated Notch signal reporter activity without exhibiting cytotoxicity against assay cells at the same concentration.

Aside from the well-studied conventional actinomycetes such as Streptomyces, the less investigated genera of actinomycetes also represent a promising source of natural products. Genome mining indicated that members of the underexplored genus Pseudosporangium, from which no secondary metabolites have been reported to date, may harbor the biosynthetic machinery for the formation of novel natural products. The strain RD062863, that is available at a public culture collection, was obtained and subjected to metabolite analysis, which resulted in the discovery of a novel cyclopeptide, pseudosporamide (1), along with three new oligomycin-class polyketides, pseudosporamicins A–C (2–4). The unusual structure of compound 1, featured by a biaryl-bond bridging across a tripeptide scaffold, N-acetyl-ʟ-Tyr-ʟ-Pro-ʟ-Trp, was determined by a combination of spectroscopic analyses, chemical derivatization, ECD calculation, and DFT-based theoretical chemical shift calculation, revealing the presence of an (Sa)-axial chirality around the biaryl bond. Compounds 2–4 lacked hydroxylation on the side chain of the spiroacetal rings, which showed clear contrast to other oligomycin congeners and related polyketides with ring-truncation or expansion. The new macrolides 2–4 displayed potent antimicrobial activity against the Gram-positive bacterium Kocuria rhizohpila and the plant pathogenic fungus Glomerella cingulata. All compounds showed moderate cytotoxicity against P388 murine leukemia cells with IC50 values in the micromolar to submicromolar ranges. These results exemplified the validity of phylogeny-focused strain selection combined with biosynthetic gene-directed genome mining for the efficient discovery of new natural products.

Star-forming galaxies with strong nebular and collisional emission lines are privileged target galaxies in forthcoming cosmological large galaxy redshift surveys. We use the COSMOS2015 photometric catalog to model galaxy spectral energy distributions and emission-line fluxes. We adopt an empirical but physically-motivated model that uses information from the best-fitting spectral energy distribution of stellar continuum to each galaxy. The emission-line flux model is calibrated and validated against direct flux measurements in subsets of galaxies that have 3D-HST or zCOSMOS-Bright spectra. We take a particular care in modelling dust attenuation such that our model can explain both H$\alpha$ and [OII] observed fluxes at different redshifts. We find that a simple solution to this is to introduce a redshift evolution in the dust attenuation fraction parameter, $f=E_{\rm star}(B-V)/E_{\rm gas}(B-V)$, as $f(z)=0.44+0.2z$. From this catalog, we derive the H$\alpha$ and [OII] luminosity functions up to redshifts of about 2.5 after carefully accounting for emission line flux and redshift errors. This allows us to make predictions for H$\alpha$ and [OII] galaxy number counts in next-generation cosmological redshift surveys. Our modeled emission lines and spectra in the COSMOS2015 catalog shall be useful to study the target selection for planned next-generation galaxy redshift surveys and we make them publicly available as `EL-COSMOS' on the ASPIC database., Comment: 21 pages, 22 figures, accepted for publication in MNRAS. Our catalog is available as "EL-COSMOS" on the ASPIC database, http://cesam.lam.fr/aspic/. A few typos corrected

Although 4-Me2NC5H4N (DMAP) is a standard base for esterification of (2-Me-6-NO2-C6H3CO)2O (MNBA), N-methylimidazole (NMI) was examined for the condensation of acids with 1-stearoyl-lysophosphatidylcholine because of the non-tailing nature of NMI on silica gel. Acids tested were EPA, α-linolenic acid, TBS ethers of 18-HEPE and ricinoleic acid, acid-labile epoxy acids, and a phenyldiynyl acid. The condensation proceeded well with these acids, and chromatographic separation of resulting phosphatidylcholines and remaining NMI was easily performed. During the characterization of the products by 13C NMR spectroscopy, 13C–14N and 13C–31P couplings were observed.

Background: Mitochondrial morphology reversibly changes between fission and fusion. As these changes (mitochondrial dynamics) reflect the cellular condition, they are one of the simplest indicators of cell state and predictors of cell fate. However, it is currently difficult to classify them using a simple and objective method. Objective: The present study aimed to evaluate mitochondrial morphology using Deep Learning (DL) technique. Methods: Mitochondrial images stained by MitoTracker were acquired from HeLa and MC3T3-E1 cells using fluorescent microscopy and visually classified into four groups based on fission or fusion. The intra- and inter-rater reliabilities for visual classification were excellent [(ICC(1,3), 0.961 for rater 1; and 0.981 for rater 2) and ICC(1,3), respectively]. The images were divided into test and train images, and a 50-layer ResNet CNN architecture (ResNet-50) using MATLAB software was used to train the images. The datasets were trained five times based on five-fold cross-validation. Result: The mean of the overall accuracy for classifying mitochondrial morphology was 0.73±0.10 in HeLa. For the classification of mixed images containing two types of cell lines, the overall accuracy using mixed images of both cell lines for training was higher (0.74±0.01) than that using different cell lines for training. Conclusion: We developed a classifier to categorize mitochondrial morphology using DL.

Notch signaling plays crucial roles in cell differentiation and proliferation, but aberrant activation of this signaling results in tumorigenesis and cancer progression. Notch signaling is thus a promising drug target for oncotherapy, and the development of Notch signaling inhibitors is eagerly awaited. Notch inhibitory activity-guided fractionation of a Spilanthes acmella extract led to the identification of five sesquiterpene lactones: tagitinin A (1), 1β,2α-epoxytagitinin C (2), tagitinin C (3), orizabin (4), and 2α-hydroxytirotundin (5). 1β,2α-Epoxytagitinin C (2) exhibited Notch signaling inhibition, with an IC50 of 25.6 μM, and was further evaluated for its activity against HPB-ALL, a Notch-activated leukemia cell line. Compound 2 showed potent cytotoxicity against HPB-ALL (IC50 1.7 μM) and arrested the cell cycle at the G2/M phase, but did not induce apoptotic cell death. Notch inhibitory mechanism analysis suggested that compound 2 transcriptionally suppresses Notch1 mRNA. In addition, we found that oxidative stress induction is critical for Notch signaling inhibition and the cytotoxicity of compound 2. This is the first mechanism of small molecule Notch inhibition. Our results demonstrate that 1β,2α-epoxytagitinin C (2) is a potential anti-leukemia agent and further investigation of this compound is warranted.

Blastocyst formation gives rise to the inner cell mass (ICM) and trophectoderm (TE) and is followed by the differentiation of the epiblast (Epi) and primitive endoderm (PrE) within the ICM. Although these two-round cell lineage differentiations underpin proper embryogenesis in every mammal, their spatiotemporal dynamics are quite diverse among species. Here, molecular details of the blastocyst stage in cattle were dissected using an optimized in vitro culture method. Blastocyst embryos were placed on agarose gel filled with nutrient-rich media to expose embryos to both gaseous and liquid phases. Embryos derived from this "on-gel" culture were transferred to surrogate mothers on day (D) 10 after fertilization and successfully implanted. Immunofluorescent studies using on-gel-cultured embryos revealed that the proportion of TE cells expressing the pluripotent ICM marker, OCT4, which was beyond 80% on D8, was rapidly reduced after D9 and reached 0% on D9.5. This first lineage segregation process was temporally parallel with the second one, identified by the spatial separation of Epi cells expressing SOX2 and PrE cells expressing SOX17. RNA-seq comparison of TE cells from D8 in vitro fertilized embryos and D14 in vivo embryos revealed that besides drastic reduction of pluripotency-related genes, TE cells highly expressed Wnt, FGF, and VEGF signaling pathways-related genes to facilitate the functional maturation required for feto-maternal interaction. Quantitative PCR analysis of TE cells derived from on-gel culture further confirmed time-dependent increments in the expression of key TE markers. Altogether, the present study provides platforms to understand species-specific strategies for mammalian preimplantation development.

We present zELDA(redshift Estimator for Line profiles of Distant Lyman-Alpha emitters), an open source code to fit Lyman-Alpha (Lya) line profiles. The main motivation is to provide the community with an easy to use and fast tool to analyze Lya line profiles uniformly to improve the understating of Lya emitting galaxies. zELDA is based on line profiles of the commonly used 'shell-model' pre-computed with the full Monte Carlo radiative transfer code LyaRT. Via interpolation between these spectra and the addition of noise, we assemble a suite of realistic Lya spectra which we use to train a deep neural network. We show that the neural network can predict the model parameters to high accuracy (e.g.,.0.34 dex HI column density for R=12000) and thus allows for a significant speedup over existing fitting methods. As a proof of concept, we demonstrate the potential of zELDA by fitting 97 observed Lya line profiles from the LASD data base. Comparing the fitted value with the measured systemic redshift of these sources, we find that Lya determines their rest frame Lya wavelength with a remarkable good accuracy of 0.3A (75 km/s). Comparing the predicted outflow properties and the observed Lya luminosity and equivalent width, we find several possible trends. For example, we find an anticorrelation between the Lya luminosity and the outflow neutral hydrogen column density, which might be explained by the radiative transfer process within galaxies, 34 pages, 23 figures. zELDA's tutorial and installation guide: https://lya-zelda.readthedocs.io/en/latest/

Escherichia albertii is an emerging zoonotic foodborne pathogen. Several outbreaks of E. albertii have occurred, particularly in Japan. Although birds have been considered as one of the most important reservoirs of this bacterium, information regarding its prevalence in birds is still scarce. We performed a survey of E. albertii in wild birds in Japan and examined the characteristics of these isolates. E. albertii-specific genes were detected in five cloacal swabs from 156 birds by PCR. Four E. albertii strains were isolated from a swallow with two different E. albertii strains and two pigeons in a flock using XRM-MacConkey agar. These isolates were assigned to biogroup 3, showed no resistance to any tested antimicrobials, and were classified into two EAO-genotypes (EAOg2 and EAOg33) and were untypable. Similar to clinical E. albertii strains, these isolates carried virulence genes, including eae (n = 4), paa (n = 4), Eccdt-I (n = 2), and stx2f (n = 1), as well as Eacdt. Furthermore, stx2f genes in a strain were located on an inducible bacteriophage, which can confer the ability to produce Stx2f in E. coli. In conclusion, Japanese wild birds carried E. albertii at levels similar to the reported prevalence in birds. These isolates may have the potential to cause gastroenteritis in humans.

We conduct intensity mapping to probe for extended diffuse Lyα emission around Lyα emitters (LAEs) at z ∼2−7, exploiting very deep (∼26 mag at 5σ) and large-area (∼4.5 deg2) Subaru/Hyper Suprime-Cam narrowband (NB) images and large LAE catalogs consisting of a total of 1540 LAEs at z = 2.2, 3.3, 5.7, and 6.6 obtained by the HSC-SSP and CHORUS projects. We calculate the spatial correlations of these LAEs with ∼1–2 billion pixel flux values of the NB images, deriving the average Lyα surface brightness (SBLyα ) radial profiles around the LAEs. By carefully estimating systematics such as fluctuations of sky background and point-spread functions, we detect Lyα emission at 100–1000 comoving kpc around z = 3.3 and 5.7 LAEs at the 3.2σ and 3.7σ levels, respectively, and tentatively (=2.0σ) at z = 6.6. The emission is as diffuse as ∼10−20–10−19 erg s−1 cm−2 arcsec−2 and extended beyond the virial radius of a dark matter halo with a mass of 1011 M ⊙. While the observed SBLyα profiles have similar amplitudes at z = 2.2–6.6 within the uncertainties, the intrinsic SBLyα profiles (corrected for the cosmological dimming effect) increase toward high redshifts. This trend may be explained by increasing hydrogen gas density due to the evolution of the cosmic volume. Comparisons with theoretical models suggest that extended Lyα emission around an LAE is powered by resonantly scattered Lyα photons in the CGM and IGM that originate from the inner part of the LAE and/or neighboring galaxies around the LAE.

A rare actinomycetal strain of the genus Actinomycetospora was found to produce a new tryptophan derivative, designated mycetoindole (1). The structure of 1 was determined to be N-3-methylcrotonoyl (Z)-dehydrotryptophan by NMR and MS analytical methods. Compound 1 reduced the root growth of lettuce Lactuca sativa seedlings at concentrations above 0.1 μM and almost completely inhibited seed germination at 10 μM.

As an extension of the study on the Hudrlik–Peterson reaction of trans-TMS-epoxy alcohols with lithium acetylides, four cis-TMS-epoxy alcohols possessing different alkyl substituents were subjected to the reaction with TMS-acetylide. The reaction completed in 1 h at 0 °C to afford cis-enynyl alcohols in good yields. The results indicated that cis-TMS-epoxy alcohols had higher reactivity than the trans-isomers. Anions derived from 1-heptyne and phenylacetylene participated in the reaction as well. The reaction was applied to optically active cis-TMS-epoxy alcohols, and the resulting enynyl alcohols were transformed to the synthetic intermediates of protectin D1, maresin 1, resolvin E1, and leukotriene B4.

14S,22-Dihydroxy-docosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (maresin-L1) and 14R,22-dihydroxy-docosa-4Z,7Z,10Z, 12E,16Z,19Z-hexaenoic acid (maresin-L2) were chemically synthesized. They were identical to activated macrophage-produced counterparts and their total synthesis was highly stereoselective, as revealed by chiral LC-UV-MS/MS analysis. The synthesis involved the following steps: (1) kinetic resolution of a racemic allylic alcohol by the asymmetric epoxidation; (2) transformation of the epoxy alcohol to γ-hydroxyenal derivative; and (3) the Wittig reaction to furnish the Z-olefin.

Cellular differentiation induces various morphological changes, including elongation, in mitochondria. Preimplantation embryos have round-shaped mitochondria, characteristic of undifferentiated cells. However, there is controversy regarding the precise mitochondrial morphology in blastocyst embryos, which are generated from two cell lineages: undifferentiated inner cell mass (ICM) and differentiated trophectoderm (TE). This study attempted to precisely determine mitochondrial morphology in these two blastocyst regions. Transmission electron microscopy analyses were conducted using more than 1000 mitochondria from blastocyst embryos. No significant differences were observed in the configuration of mitochondrial cristae and frequencies of hooded mitochondria, which are specific to embryos of livestock animals, between the ICM and TE. To accurately compare mitochondrial roundness between the ICM and TE, oblateness was calculated based on both the major and minor axes. Average oblateness was significantly greater in the TE than in the ICM (P < 0.01). These results indicate tissue-specific mitochondrial maturation with complete elongation in the TE at the blastocyst stage. Since mitochondrial elongation is closely associated with cellular metabolism and differentia-tion, the present study provides new insights for better understanding of early embryonic develop-ment in cattle. (c) 2021 Elsevier Inc. All rights reserved.

The density field reconstruction technique has been widely used for recovering the Baryon Acoustic Oscillation (BAO) feature in galaxy surveys that has been degraded due to nonlinearities. Recent studies advocated adopting iterative steps to improve the recovery much beyond that of the standard technique. In this paper, we investigate the performance of a few selected iterative reconstruction techniques focusing on the BAO and the broadband-shape of the two-point clustering. We include redshift-space distortions, halo bias, and shot noise and inspect the components of the reconstructed field in Fourier space and in configuration space using both density field-based reconstruction and displacement field-based reconstruction. We find that the displacement field reconstruction becomes quickly challenging in the presence of non-negligible shot noise and therefore present surrogate methods that can be practically applied to a much more sparse field such as galaxies. For a galaxy field, implementing a debiasing step to remove the Lagrangian bias appears crucial for the displacement field reconstruction. We show that the iterative reconstruction does not substantially improve the BAO feature beyond an aggressively optimized standard reconstruction with a small smoothing kernel. However, we find taking iterative steps allows us to use a small smoothing kernel more `stably', i.e., without causing a substantial deviation from the linear power spectrum on large scales. In one specific example we studied, we find that a deviation of 13\% in $P( k \sim 0.1h/Mpc)$ with an aggressive standard reconstruction can reduce to 3-4\% with iterative steps., Comment: 17 pages, 12 figures, 2 tables. Corrected for minor inconsistencies related to bias and RSD treatment during iterative reconstruction. All relevant figures are updated, while the results stay almost the same

We explore how to mitigate the clustering distortions in Lyman-$\alpha$ emitters (LAEs) samples caused by the miss-identification of the Lyman-$\alpha$ (Ly$\alpha$) wavelength in their Ly$\alpha$ line profiles. We use the Ly$\alpha$ line profiles from our previous LAE theoretical model that includes radiative transfer in the interstellar and intergalactic mediums. We introduce a novel approach to measure the systemic redshift of LAEs from their Ly$\alpha$ line using neural networks. In detail, we assume that, for a fraction of the whole LAE population their systemic redshift is determined precisely through other spectral features. We then use this subset to train a neural network that predicts the Ly$\alpha$ wavelength given a Ly$\alpha$ line profile. We test two different training sets: i) the LAEs are selected homogeneously and ii) only the brightest LAEs are selected. In comparison with previous approaches in the literature, our methodology improves significantly both accuracy and precision in determining the Ly$\alpha$ wavelength. In fact, after applying our algorithm in ideal Ly$\alpha$ line profiles, we recover the clustering unperturbed down to 1cMpc/h. Then, we test the performance of our methodology in realistic Ly$\alpha$ line profiles by downgrading their quality. The machine learning techniques work well even if the Ly$\alpha$ line profile quality is decreased considerably. We conclude that LAE surveys such as HETDEX would benefit from determining with high accuracy the systemic redshift of a subpopulation and applying our methodology to estimate the systemic redshift of the rest of the galaxy sample., Comment: 24 Pages, 16 figures, a lot of fun

Purpose To assess the outcomes of high-dose-rate (HDR) brachytherapy and hypofractionated external beam radiation therapy (EBRT) combined with long-term androgen deprivation therapy (ADT) in very-high-risk (VHR) versus high-risk (HR) prostate cancer (PCa), as defined in the National Comprehensive Cancer Network (NCCN) criteria. Methods Data from 338 consecutive HR or VHR PCa patients who had undergone this tri-modal therapy between 2005 and 2018 were retrospectively analyzed. Biochemical recurrence (BCR)-free, progression-free, overall, and cancer-specific survival (BCRFS/PFS/OS/CSS) rates were analyzed using the Kaplan–Meier method and Wilcoxon test. Cox regression models were used to evaluate candidate prognostic factors for survival. C‑indexes were used to assess model discrimination. Results Within a median follow-up of 84 months, 68 patients experienced BCR, 58 had disease progression including only 3 with local progression, 27 died of any cause, and 2 died from PCa. The 5‑year BCRFS, PFS, OS, and CSS rates were 82.2% (HR 86.5%; VHR 70.0%), 90.0% (HR 94.3%; VHR 77.6%), 95.7% (HR, 97.1%; VHR, 91.8%), and 99.6% (HR, 100%; VHR, 98.0%), respectively. In multivariable analyses that adjusted for standard clinicopathologic features, the risk subclassification was associated both PFS and OS (p = 0.0003 and 0.001, respectively). Adding the risk subclassification improved the accuracy of models in predicting BCRFS, PFS, and OS. Conclusion While the outcome of this trimodal approach appears favorable, VHR PCa patients had significantly worse oncological outcomes than those with HR PCa. The NCCN risk subclassification should be integrated into prognostic tools to guide risk stratification, treatment, and follow-up for unfavorable PCa patients receiving this trimodal therapy.

We present the results of cosmological simulations of large-scale structure formation with massive neutrinos. The phase-space distribution of the cosmic relic neutrinos is followed, for the first time, by directly integrating the six-dimensional Vlasov-Poisson equations. Our novel approach allows us to represent free streaming and clustering of neutrinos, and their gravitational interaction with cold dark matter accurately. We thus obtain solutions for the collisionless dynamics independent of conventional N-body methods. We perform a suite of hybrid N-body/Vlasov simulations with varying the neutrino mass, and systematically examine the dynamical effects of massive neutrinos on large-scale structure formation. Our simulations show characteristic large-scale clustering of the neutrinos and their coherent streaming motions relative to dark matter. The effective local neutrino "temperature" around massive galaxy clusters varies by several percent with respect to the cosmic mean; the neutrinos in clusters can be hotter or colder depending on the neutrino mass. We study a number of statistics of the large-scale structure and of dark matter halos in comparison with those obtained by N-body simulations and/or by perturbation theory. Our simulations mark an important milestone in numerical cosmology, and pave a new way to study cosmic structure formation with massive neutrinos., 21 pages, accepted for publication in ApJ