An E3-like Factor that Promotes SUMO Conjugation to the Yeast Septins

AbstractCovalent attachment of the ubiquitin-related protein SUMO to other proteins participates in many processes including signal transduction, transcriptional regulation, and growth control. We report the characterization of Siz1 as an E3-like factor in the SUMO pathway. Siz1 is required for SUMO attachment to the S. cerevisiae septins in vivo and strongly stimulates septin sumoylation in vitro. Siz1 and the related protein Siz2 promote SUMO conjugation to different substrates at different stages of the cell cycle and, together, are required for most SUMO conjugation in yeast. Siz1, Siz2, and the PIAS (protein inhibitor of activated STAT) proteins form a conserved family defined by an unusual RING-related motif. Our results suggest that this family functions by promoting SUMO conjugation to specific substrates

Impact of tidal environment on galaxy populations using GAMA

We present constraints on models of the galaxy distribution in the cosmic web using a magnitude limited sample from the Galaxy and Mass Assembly (GAMA) survey. We model the redshift-space behaviour of the 2-point correlation function (2pcf) and the recently proposed Voronoi volume function (VVF) -- which includes information beyond 2-point statistics. We extend the standard halo occupation distribution model by introducing extra satellite degrees of freedom, and also by including two assembly bias parameters, $\alpha_{\rm cen}$ and $\alpha_{\rm sat}$, which respectively correlate the occupation numbers of central and satellite galaxies with their host halo's tidal environment. We measure $\alpha_{\rm sat}=1.44^{+0.25}_{-0.43}$ and $\alpha_{\rm cen}=-0.79^{+0.29}_{-0.11}$ using a combination of 2pcf and VVF measurements. These represent a detection of assembly bias at the 3.3$\sigma$ (2.4$\sigma$) significance level for satellite (central) galaxies, a result that remains robust to possible anisotropies in the halo-centric distribution of satellites as well as technicalities of estimating the data covariance. We show that the growth rate ($f\sigma_8$) deduced using models with assembly bias is about 7\% (i.e. $1.5\sigma$) lower than if assembly bias is ignored. Projecting $f\sigma_8$ onto the $\Omega_m$-$\sigma_8$ plane, we find that the model constraints without assembly bias overlap with Planck expectations, but that allowing assembly bias introduces significant tension with Planck, preferring either a lower $\Omega_m$ or a lower $\sigma_8$. We also study the effect of assembly bias on the weak lensing signal. While the all-galaxy lensing signal is unaffected, both central and satellite sub-populations individually show significantly different signals in the presence of assembly bias. [abridged]Comment: 17 pages, 14 figures, 2 tables, submitted for revie

The Spatial Averaging Limit of Covariant Macroscopic Gravity - Scalar Corrections to the Cosmological Equations

It is known that any explicit averaging scheme of the type essential for describing the large scale behaviour of the Universe, must necessarily yield corrections to the Einstein equations applied in the Cosmological setting. The question of whether or not the resulting corrections to the Einstein equations are significant, is still a subject of debate, partly due to possible ambiguities in the averaging schemes available. In particular, it has been argued in the literature that the effects of averaging could be gauge artifacts. We apply the formalism of Zalaletdinov's Macroscopic Gravity (MG) which is a fully covariant and nonperturbative averaging scheme, in an attempt to construct gauge independent corrections to the standard Friedmann-Lemaitre-Robertson-Walker (FLRW) equations. We find that whereas one cannot escape the problem of dependence on \emph{one} gauge choice -- which is inherent in the assumption of large scale homogeneity and isotropy -- it is however possible to construct \emph{spacetime scalar} corrections to the standard FLRW equations. This partially addresses the criticism concerning the corrections being gauge artifacts. For a particular initial choice of gauge which simplifies the formalism, we explicitly construct these scalars in terms of the underlying inhomogeneous geometry, and incidentally demonstrate that the formal structure of the corrections with this gauge choice is identical to that of analogous corrections derived by Buchert in the context of spatial averaging of scalars.Comment: 18 pages, no figures, revtex4; v2 - minor clarifications added; v3 - minor changes in presentation to improve clarity, reference added, to appear in Phys. Rev.

Proximal Hypospadias

Hypospadias results from abnormal development of the penis that leaves the urethral meatus proximal to its normal glanular position. Meatal position may be located anywhere along the penile shaft, but more severe forms of hypospadias may have a urethral meatus located at the scrotum or perineum. The spectrum of abnormalities may also include ventral curvature of the penis, a dorsally redundant prepuce, and atrophic corpus spongiosum. Due to the severity of these abnormalities, proximal hypospadias often requires more extensive reconstruction in order to achieve an anatomically and functionally successful result. We review the spectrum of proximal hypospadias etiology, presentation, correction, and possible associated complications

Recurrence Risk Stratification for Women with FIGO Stage I Uterine Endometrioid Carcinoma Who Underwent Surgical Lymph Node Evaluation

Purpose/Objective(s): To estimate the recurrence risk based on the number of prognostic factors in women with FIGO stage I uterine endometrioid carcinoma (EC) in a large cohort of patients who underwent surgical staging including surgical lymph node evaluation (SLNE) and were managed with no adjuvant therapy. Materials/Methods: We queried our in-house prospectively maintained uterine cancer database for patients with FIGO stage I EC underwent surgical staging including SLNE between 1/1990-12/2020. Patients with synchronous ovarian and breast cancer diagnosis were excluded as well as those who received adjuvant therapy of any form. Patient\u27s demographics and pathologic variables were analyzed. We used multivariate analysis (MVA) with Stepwise Model Selection to determine risk factors for 5-year recurrence-free survival (RFS). Study population was then stratified based on the number of risk factors identified (0, 1 or 2). The resultant groups were compared for RFS, disease-specific survival (DSS) and overall survival (OS) using log-rank test and Kaplan-Meier curves. Additionally, independent predictors of DSS and overall OS were estimated. Results: 706 patients were identified who met our inclusion criteria with a median age of 60 years (range, 30-93) and a median follow-up of 120 months. All patients had at least pelvic SLNE with a median number of examined lymph node (LN) of 8 (range, 1-66): 66 patients (11%) had a sentinel LN sampling and 43% had paraaortic SLNE. 639 patients (91%) were stage IA and lymphovascular space invasion (LVSI) was detected in 6% (n=41). Recurrence was diagnosed in 44 patients (6%). Independent predictors of 5-year RFS include age ≥ 60 years (p=0.038), grade 2 vs. 1 (p=0.003), and grade 3 vs 1 (p\u3c0.001). 5-year RFS for group-0 (age \u3c 60 years and grade 1) was 98% vs. 92% for group-1 (either: age ≥ 60 years or grade 2/3) vs 84% for group-2 (both: age ≥ 60 years and grade 2/3), respectively (p\u3c0.001). 5- year DSS for the three groups was (100% vs 98% vs 95%, p=0.012) and 5-year OS was (98% vs 90% vs 81%, p\u3c0.001), respectively. On MVA, stage IB vs IA was deterministic for DSS (p=0.02); whereas age ≥ 60 years (p\u3c0.001) and grade 3 vs grade 1 (p=0.004) were predictors for worse OS. Conclusion: In patients with stage I endometrioid carcinoma who had surgical staging including SLNE and no adjuvant therapy, only age ≥ 60 years and high tumor grade were independent predictors of cancer recurrence and hence can be used to quantify individualized recurrence risk. Surprisingly, LVSI was not an independent prognostic factor in this study cohort with SLNE

Backreaction of Cosmological Perturbations in Covariant Macroscopic Gravity

The problem of corrections to Einstein's equations arising from averaging of inhomogeneities ("backreaction") in the cosmological context, has gained considerable attention recently. We present results of analysing cosmological perturbation theory in the framework of Zalaletdinov's fully covariant Macroscopic Gravity. We show that this framework can be adapted to the setting of cosmological perturbations in a manner which is free from gauge related ambiguities. We derive expressions for the backreaction which can be readily applied in \emph{any} situation (not necessarily restricted to the linear perturbations considered here) where the \emph{metric} can be brought to the perturbed FLRW form. In particular these expressions can be employed in toy models studying nonlinear structure formation, and possibly also in N-body simulations. Additionally, we present results of example calculations which show that the backreaction remains negligible well into the matter dominated era.Comment: 17 pages, 5 figures, revtex4; v2 -- typos fixed, 1 reference updated, to appear in Phys Rev

The Prognostic Significance of the Depth of Cervical Stromal Invasion in Women with FIGO Stage II Uterine Endometrioid Carcinoma

Purpose/Objective(s): To explore the prognostic significance of the depth of cervical stromal invasion (CSI) on survival endpoints in women with FIGO stage II uterine endometrioid adenocarcinoma. Materials/Methods: A total of 117 patients were included in this retrospective review. Between 1990 and 2021, all patients with FIGO stage II endometrial cancer (EC) underwent hysterectomy and oophorectomy at our institution, with or without lymph node dissection. Patients with synchronous ovarian or breast cancer, as well as those who had undergone adjuvant systemic chemotherapy for EC, were excluded from the study. Pathologic slides were retrieved for these patients and were reviewed by a gynecologic pathologist to determine stromal thickness and the depth of CSI. The depth of CSI was then measured as a percentage of invasion (% CSI) and used in the analysis as a continuous or dichotomous variable (\u3c 50% vs \u3e = 50%). Patients\u27 demographics, pathologic, and treatment characteristics were analyzed using univariate and multivariate analysis to calculate recurrence-free (RFS) and disease-specific (DSS) rates. Results: The median age for the study cohort was 65 years (range, 34–96), and the median follow-up was 131 months (range, 9–334). A total of 90 patients (77%) had lymph node dissection, with a median of 8 examined lymph nodes (range 0-18). Adjuvant radiation therapy (RT) with pelvic or vaginal cuff HDR brachytherapy, or a combination of the two, was completed in 92 patients (79 percent). The median % CSI was 27% (range, 1-100) with 68% of patients having ≥ 50% CSI. While there was a trend for a worse 5-year RFS and DSS for women with ≥ 50% CSI (69% vs. 83%, p = 0.093) and (78% vs. 91%, p = 0.034), respectively, the depth of CSI was not statistically significant as an independent predictor of 5-year RFS, DSS, or OS. The depth of CSI was not associated with a difference in the recurrence pattern (vaginal cuff, pelvic, paraaortic, or distant). In multivariate analysis, FIGO grade was the only predictor of 5-year OS. FIGO grade and the presence of lympho-vascular space invasion (LVSI) were independent predictors of 5-year RFS and DSS. Conclusion: Deep cervical stromal invasion does not appear to be an independent predictive factor for survival endpoints in women with stage II uterine endometroid cancer, according to our findings. The presence of LVSI and tumor grade were both independent predictors of recurrence-free and disease-specific survival. Pooled data analysis may be needed to validate our study findings

Intelligent Motion Detection and Tracking System

The rapid development in the field of digital image processing made motion detection and tracking an attractive research topic. Until recent years, real-time video applications were inapplicable due to the expense computational time. An intelligent method to analyze the motion in a stream video line using the methods of background subtraction, temporal differencing, and optical flow, methods are proposed. The new method solves the computational time problem by using a reliable technique that is called Fast Pixels Selection. A low cost tracking system is proposed. This tracking system consist of camera, PC, motor and data acquisition card. This system is designed to detect and track any moving target automatically

Systematic Review and Regression Modeling of the Effects of Age, Body Size, and Exercise on Cardiovascular Parameters in Healthy Adults

Purpose Blood pressure, cardiac output, and ventricular volumes correlate to various subject features such as age, body size, and exercise intensity. The purpose of this study is to quantify this correlation through regression modeling. Methods We conducted a systematic review to compile reference data of healthy subjects for several cardiovascular parameters and subject features. Regression algorithms used these aggregate data to formulate predictive models for the outputs—systolic and diastolic blood pressure, ventricular volumes, cardiac output, and heart rate—against the features—age, height, weight, and exercise intensity. A simulation-based procedure generated data of virtual subjects to test whether these regression models built using aggregate data can perform well for subject-level predictions and to provide an estimate for the expected error. The blood pressure and heart rate models were also validated using real-world subject-level data. Results The direction of trends between model outputs and the input subject features in our study agree with those in current literature. Conclusion Although other studies observe exponential predictor-output relations, the linear regression algorithms performed the best for the data in this study. The use of subject-level data and more predictors may provide regression models with higher fidelity. Significance Models developed in this study can be useful to clinicians for personalized patient assessment and to researchers for tuning computational models

Quantitative microarray profiling of DNA-binding molecules

A high-throughput Cognate Site Identity (CSI) microarray platform interrogating all 524 800 10-base pair variable sites is correlated to quantitative DNase I footprinting data of DNA binding pyrrole-imidazole polyamides. An eight-ring hairpin polyamide programmed to target the 5 bp sequence 5'-TACGT-3' within the hypoxia response element (HRE) yielded a CSI microarray-derived sequence motif of 5'-WWACGT-3' (W = A,T). A linear beta-linked polyamide programmed to target a (GAA)_3 repeat yielded a CSI microarray-derived sequence motif of 5'-AARAARWWG-3' (R = G,A). Quantitative DNase I footprinting of selected sequences from each microarray experiment enabled quantitative prediction of K_a values across the microarray intensity spectrum