Near-Zone Symmetries of Kerr Black Holes

We study the near-zone symmetries of a massless scalar field on four-dimensional black hole backgrounds. We provide a geometric understanding that unifies various recently discovered symmetries as part of an SO(4,2) group. Of these, a subset are exact symmetries of the static sector and give rise to the ladder symmetries responsible for the vanishing of Love numbers. In the Kerr case, we compare different near-zone approximations in the literature, and focus on the implementation that retains the symmetries of the static limit. We also describe the relation to spin-1 and 2 perturbations.Comment: 4+3 pages, 1 figur

AntiHunter 2.0: increased speed and sensitivity in searching BLAST output for EST antisense transcripts

An increasing number of eukaryotic and prokaryotic genes are being found to have natural antisense transcripts (NATs). There is also growing evidence to suggest that antisense transcription could play a key role in many human diseases. Consequently, there have been several recent attempts to set up computational procedures aimed at identifying novel NATs. Our group has developed the AntiHunter program for the identification of expressed sequence tag (EST) antisense transcripts from BLAST output. In order to perform an analysis, the program requires a genomic sequence plus an associated list of transcript names and coordinates of the genomic region. After masking the repeated regions, the program carries out a BLASTN search of this sequence in the selected EST database, reporting via email the EST entries that reveal an antisense transcript according to the user-supplied list. Here, we present the newly developed version 2.0 of the AntiHunter tool. Several improvements have been added to this version of the program in order to increase its ability to detect a larger number of antisense ESTs. As a result, AntiHunter can now detect, on average, >45% more antisense ESTs with little or no increase in the percentage of the false positives. We also raised the maximum query size to 3 Mb (previously 1 Mb). Moreover, we found that a reasonable trade-off between the program search sensitivity and the maximum allowed size of the input-query sequence could be obtained by querying the database with the MEGABLAST program, rather than by using the BLAST one. We now offer this new opportunity to users, i.e. if choosing the MEGABLAST option, users can input a query sequence up to 30 Mb long, thus considerably improving the possibility to analyze longer query regions. The AntiHunter tool is freely available at

Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty

Background: Frailty is an important outcome predictor in patients with aortic stenosis who are candidates for transcatheter or surgical aortic valve replacement (AVR). Growth/differentiation factor 15 (GDF15) is a cytokine playing a role in the pathophysiology of ventricular remodeling. We assessed its potential role as an independent soluble biomarker of frailty in these patients. Methods: We studied 62 patients (age, mean 79 years, 95% confidence interval (CI) 77-81; 54.8% female) with severe aortic valve stenosis and candidates for AVR. We systematically assessed pre-intervention GDF15 levels for their relationship with frailty (Katz score) and echocardiographic parameters of left ventricular dysfunction/remodeling. Fifteen hypertensive patients with left ventricular (LV) hypertrophy served as controls. Results: Patients with aortic valve stenosis featured higher GDF15 levels than controls (1773, 95% CI 1574-1971 pg/mL vs. 775, 95% CI 600-950 pg/mL, respectively, p < 0.0001). Subjects in the upper GDF15 tertile were older (p = 0.004), with a more advanced NYHA functional class (p = 0.04) and a higher prevalence of impaired renal function (p = 0.004). Such patients also showed a higher frailty score (p = 0.04) and higher indices of LV dysfunction, including reduced global longitudinal strain (p = 0.01) and a higher left ventricular mass (p = 0.001). GDF15 was significantly related to the Katz score, and predicted (OR 1.05; 95% CI 0.9-1.1; p = 0.03) a low (<5) Katz score, independent of the relationship with LV mass, age, renal function or indices of LV dysfunction. Conclusions: GDF15 is increased in patients with severe aortic stenosis and appears to be a soluble correlate of patients' frailty, independent of indices of left ventricular dysfunction

Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma

Urothelial carcinoma (UC) is a frequent cause of cancer-related deaths worldwide. Metastatic UC has been historically associated with poor prognosis, with a median overall survival of approximately 15 months and a 5-year survival rate of 18%. Although platinum-based chemotherapy remains the mainstay of medical treatment for patients with metastatic UC, chemotherapy clinical trials produced modest benefit with short-lived, disappointing responses. In recent years, the better understanding of the role of immune system in cancer control has led to the development and approval of several immunotherapeutic approaches in UC therapy, where immune checkpoint inhibitors have been revolutionizing the treatment of metastatic UC. Because of a better tumor molecular profiling, FGFR inhibitors, PARP inhibitors, anti-HER2 agents, and antibody drug conjugates targeting Nectin-4 are also emerging as new therapeutic options. Moreover, a wide number of trials is ongoing with the aim to evaluate several other alterations and pathways as new potential targets in metastatic UC. In this review, we will discuss the recent advances and highlight future directions of the medical treatment of UC, with a particular focus on recently published data and ongoing active and recruiting trials

Temporal lobe (TL) damage following surgery and high-dose photon and proton irradiation in 96 patients affected by chordomas and chondrosarcomas of the base of the skull

Purpose: To determine the temporal lobe (TL) damage rate in 96 patients treated with high-dose proton and photon irradiation for chordomas and chondrosarcomas of the base of the skull. Methods and Materials: The records of 96 consecutive patients treated at Massachusetts General Hospital (MGH) and Harvard Cyclotron Laboratory (HCL) between June 1984 and 1993, for chordomas and chondrosarcomas of the base of the skull were reviewed. All the patients had undergone some degree of resection of the tumor prior to radiation therapy. Seventy-five patients were classified as 'primary tumors' and 21 as recurrent or regrowing tumors after one or more surgical procedures. All the patients were randomized to receive 66.6 or 72 cobalt Gray equivalent (CGE) on a prospective dose-searching study by proton and photon irradiation (Radiation Therapy Oncology Group No.85-26) with conventional fractionation (1.8 CGE/day, 5 fractions/week). All treatments were planned using the three-dimensional (3D) planning system developed at the Massachusetts General Hospital, and the dose was delivered using opposed lateral fields for the photon component and a noncoplanar isocentric technique for the proton component. Clinical symptoms of TL damage were classified into 4 grades. Computerized tomography (CT) and magnetic resonance imaging (MRI) scans were evaluated for white matter changes. Abnormalities associated with persistent or recurrent tumor were distinguished from radiation-induced changes. TLs were delineated on the original scans of the 10 patients with damage and those of a group of 33 patients with no clinical or MRI evidence of injury. Dose distributions were calculated and dose- volume histograms were obtained for these patients. Results: Of the patients, 10 developed TL damage, with bilateral injury in 2 and unilateral injury in 8. The cumulative TL damage incidence at 2 and 5 years was 7.6 and 13.2%, respectively. The MRI areas suggestive of TL damage were always separated from the tumor bed. Symptoms were severe to moderate in 8 patients. Several baseline factors, tumor- or host-related, were analyzed to evaluate their predictivity for TL damage: age, gender, tumor site, histology, type of presentation, type and number of surgical procedures, primary tumor volume, prescribed dose, normal tissue involvement, and volume of TL receiving doses ranging between 10 and 50 CGE or more. Only gender, in a univariate analysis (log rank) was a significant predictor of damage (0.0155), with male patients being at significantly higher risk of TL injury. In a stepwise Cox regression that included gender as a variable, no other baseline variable improved the prediction of damage. Conclusions: The 2- and 5-year cumulative TL damage rates were 7.6 and 13.2%, respectively. Despite the different TL damage rates related to age, tumor volume, number of surgical procedures prior to radiation therapy, and prescribed doses to the tumor, only gender was a significant predictor of damage (p = 0.0155) using a univariate (log rank) test. Chordomas and chondrosarcomas of the base of the skull may represent an interesting model to evaluate the TL damage rates because of their extradural origin, displacing the white matter instead of infiltrating it as gliomas do, because of their longer local recurrence-free survival other than gliomas and other brain tumors and because of the high doses of irradiation delivered to the target volume to obtain local control

From BEXUS to HEMERA: The application of lessons learned on the development and manufacturing of stratospheric payloads at S5Lab

In the last years the S5Lab (Sapienza Space Systems and Space Surveillance Laboratory) from Sapienza University of Rome has given to the students the opportunity to gather knowledge on stratospheric payloads by supporting the design and development of two experiments selected for the participation in the REXUS/BEXUS educational Programme, managed by three european space institutions. The insights and lessons learned gathered during the participations in the REXUS/BEXUS educational programme gave the possibility to the student to take part in the development of a third experiment in the frame of the professional research programme HEMERA and complete it successfully. STRATONAV (STRATOspheric NAVigation experiment) was a stratospheric experiment based on Software Defined Radios (SDRs) technology whose aim was the testing of the VOR (VHF Omnidirectional Range) navigation system, evaluating its performance above the standard service volume, which was launched on BEXUS 22 in October 2016. TARDIS (Tracking and Attitude Radio-based Determination In Stratosphere) was developed as a follow up of STRATONAV between 2018 and 2019. Similarly to its predecessor TARDIS was a stratospheric experiment aimed at exploiting the VOR signal, with the aid of SDRs, to perform in-flight attitude and position determination, and was launched on BEXUS 28 in October 2019. After the launch of TARDIS, a team composed both by former STRATONAV and TARDIS students was formed for the development of a third stratospheric experiment going by the name of STRAINS (Stratospheric Tracking Innovative Systems), conceived by Sapienza University of Rome and ALTEC and supported by ASI. STRAINS main objective was the proof of concept of the possibility of achieving the Time Difference of Arrival (TDOA) and the Frequency Difference of Arrival (FDOA) for navigation purposes with the aid of SDRs. The experiment was developed between 2020 and 2021 exploiting the lessons learned from the former team members of the two BEXUS campaigns and was launched on board of the Hemera H2020 stratospheric balloon in September 2021 from Esrange Space Center, Kiruna, Sweden. After a brief description of the stratospheric payloads design and manufacturing, the paper will present the major lessons learned from the previous stratospheric experiments, STRATONAV and TARDIS, and their application to the development and manufacturing of the latest launched stratospheric experiment STRAINS, as well as their educational return to the students involved in the projects

Designing greenhouse subsystems for a lunar mission: the LOOPS - M Project

The 2020s is a very important decade in the space sector, where international cooperation is moving towards the exploration of the Moon and will lead to stable lunar settlements, which will require new, innovative, and efficient technologies. In this context, the project LOOPS–M (Lunar Operative Outpost for the Production and Storage of Microgreens) was created by students from Sapienza University of Rome with the objective of designing some of the main features of a lunar greenhouse. The project was developed for the IGLUNA 2021 campaign, an interdisciplinary platform coordinated by Space Innovation as part of the ESA Lab@ initiative. The LOOPS-M mission was successfully concluded during the Virtual Field Campaign that took place in July 2021. This project is a follow-up of the V-GELM Project, which took part in IGLUNA 2020 with the realization in Virtual Reality of a Lunar Greenhouse: a simulation of the main operations connected to the cultivation module, the HORT3 , which was already developed by ENEA (Italian National Agency for New Technologies, Energy and Sustainable Economic Development) during the AMADEE-18 mission inside the HORTSPACE project. This paper will briefly describe the main features designed and developed for the lunar greenhouse and their simulation in a VR environment: an autonomous cultivation system able to handle the main cultivation tasks of the previous cultivation system, a bioconversion system that can recycle into new resources the cultivation waste with the use of insects as a biodegradation system, and a shield able of withstanding hypervelocity impacts and the harsh lunar environment. A wide overview of the main challenges faced, and lessons learned by the team to obtain these results, will be given. The first challenge was the initial inexperience that characterized all the team members, being for most the first experience with an activity structured as a space mission, starting with little to no know-how regarding the software and hardware needed for the project, and how to structure documentation and tasks, which was acquired throughout the year. An added difficulty was the nature of LOOPS-M, which included very different objectives that required different fields of expertise, ranging from various engineering sectors to biology and entomology. During the year, the team managed to learn how to handle all these hurdles and the organizational standpoint, working as a group, even if remotely due to the Covid-19 pandemic. Through careful planning, hard work and the help of supervisors, the activity was carried out through reviews, up to the prototyping phase and the test campaign with a successful outcome in each aspect of the project. By the end of the year everyone involved had acquired new knowledge, both practical and theoretical, and learned how to reach out and present their work to sponsors and to the scientific community

The Exploration and Practice of Party Member of College Students rdquo;Recognizing Position and Taking Responsibility for a Model”

AbstractNowadays, it has become more important to strengthen the education, management and training work of the party members of college students. Our school has carried out the party members of college students. rdquo;recognizing position and taking responsibility for a model” activity for two years. And obtained some experience. The party members of college students rdquo;recognizing position and taking responsibility for a model” activity should set up scientific positions, define their responsibilities clearly and strengthen the management and assessment

TNM staging towards a personalized approach in metastatic urothelial carcinoma: what will the future be like?—a narrative review

The American Joint Committee of Cancer (AJCC) tumor-node-metastasis (TNM) classification, with its periodical updates and modifications, has represented and still represents the basis of cancer staging. The historical, long-standing limitations of anatomic-based TNM staging have been recently “threatened” by the impressive amount of data derived from molecular analyses, which have led to an unprecedented level of understanding of cancer genomics. In fact, current era of personalized oncology has witnessed important efforts towards the integration between clinical, anatomical and molecular features; however, despite the promises, personalized oncology faces many obstacles, due to the complex relationship between tumor biomarkers, previously unknown cancer subtypes and clinical and anatomical characteristics. With regard to urothelial carcinoma (UC), the characterization of tumors in large cohorts of patients has provided important information concerning genetic alterations, revealing the presence of biologically relevant subtypes of UC. In the current review, we will provide an overview regarding this recent “translation” from the anatomic-based TNM to a novel horizon, aiming at further “tailoring” personalized oncology, especially focusing on recently published data about the molecular landscape of UC with its therapeutic and prognostic implications

Cabozantinib After a Previous Immune Checkpoint Inhibitor in Metastatic Renal Cell Carcinoma: A Retrospective Multi-Institutional Analysis

Background: Angiogenesis has been recognized as the most important factor for tumor invasion, proliferation, and progression in metastatic renal cell carcinoma (mRCC). However, few clinical data are available regarding the efficacy of cabozantinib following immunotherapy. Objective: To describe the outcome of cabozantinib in patients previously treated with immunotherapy. Patients and methods: Patients with mRCC who received cabozantinib immediately after nivolumab were included. The primary endpoint was to assess the outcome in terms of efficacy and activity. Results: Eighty-four mRCC patients met the criteria to be included in the final analysis. After a median follow-up of 9.4 months, median overall survival was 17.3 months. According to the IMDC criteria, the rates of patients alive at 12 months in the good, intermediate, and poor prognostic groups were 100%, 74%, and 33%, respectively (p < 0.001). The median progression-free survival (PFS) was 11.5 months (95% CI 8.3-14.7); no difference was found based on duration of previous first-line therapy or nivolumab PFS. The overall response rate was 52%, stable disease was found as the best response in 25.3% and progressive disease in 22.7% of patients. Among the 35 patients with progressive disease on nivolumab, 26 (74.3%) patients showed complete/partial response or stable disease with cabozantinib as best response after nivolumab. The major limitations of this study are the retrospective nature and the short follow-up. Conclusions: Cabozantinib was shown to be effective and active in patients previously receiving immune checkpoint inhibitors. Therefore, cabozantinib can be considered a valid therapeutic option for previously treated mRCC patients, irrespective of the type and duration of prior therapies