Analyzing Declarative Deployment Code with Large Language Models

In the cloud-native era, developers have at their disposal an unprecedented landscape of services to build scalable distributed systems. The DevOps paradigm emerged as a response to the increasing necessity of better automations, capable of dealing with the complexity of modern cloud systems. For instance, Infrastructure-as-Code tools provide a declarative way to define, track, and automate changes to the infrastructure underlying a cloud application. Assuring the quality of this part of a code base is of utmost importance. However, learning to produce robust deployment specifications is not an easy feat, and for the domain experts it is time-consuming to conduct code-reviews and transfer the appropriate knowledge to novice members of the team. Given the abundance of data generated throughout the DevOps cycle, machine learning (ML) techniques seem a promising way to tackle this problem. In this work, we propose an approach based on Large Language Models to analyze declarative deployment code and automatically provide QA-related recommendations to developers, such that they can benefit of established best practices and design patterns. We developed a prototype of our proposed ML pipeline, and empirically evaluated our approach on a collection of Kubernetes manifests exported from a repository of internal projects at Nokia Bell Labs

Implications of SARS-COV-2 infection in the diagnosis and management of the pediatric gastrointestinal disease

Gastrointestinal diseases such as celiac disease, functional gastrointestinal disorders (FGIDs), inflammatory bowel disease (IBDs) and acute or chronic diarrhea are quite frequent in the pediatric population. The approach, the diagnosis and management can be changed in the 2019 coronavirus disease (COVID-19) pandemic era. This review has focused on: i) the current understanding of digestive involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected children and adolescents and the clinical implications of COVID-19 for pediatric gastroenterologists, ii) the impact of COVID-19 on the clinical approach to patients with pre-existing or onset diseases, including diagnosis and treatment, and iii) the role and limited access to the instrumental diagnosis such as digestive endoscopy. To date, it is unclear if immunosuppression in patients with IBD and chronic liver disease represents a risk factor for adverse outcomes. Scheduled outpatient follow-up visits may be postponed, especially in patients in remission. Conversely, telemedicine services are strongly recommended. The introduction of new therapeutic regimens should be made on an individual basis, discussing the benefits and risks with each patient. Furthermore, psychological care in all children with chronic disease and their parents should be ensured. All non-urgent and elective endoscopic procedures may be postponed as they must be considered at high risk of viral transmission. Finally, until SARS-CoV-2 vaccination is not available, strict adherence to standard social distancing protocols and the use of personal protective equipment should continue to be recommended

The ALTCRISS project on board the International Space Station

The Altcriss project aims to perform a long term survey of the radiation environment on board the International Space Station. Measurements are being performed with active and passive devices in different locations and orientations of the Russian segment of the station. The goal is to perform a detailed evaluation of the differences in particle fluence and nuclear composition due to different shielding material and attitude of the station. The Sileye-3/Alteino detector is used to identify nuclei up to Iron in the energy range above 60 MeV/n. Several passive dosimeters (TLDs, CR39) are also placed in the same location of Sileye-3 detector. Polyethylene shielding is periodically interposed in front of the detectors to evaluate the effectiveness of shielding on the nuclear component of the cosmic radiation. The project was submitted to ESA in reply to the AO in the Life and Physical Science of 2004 and data taking began in December 2005. Dosimeters and data cards are rotated every six months: up to now three launches of dosimeters and data cards have been performed and have been returned with the end of expedition 12 and 13.Comment: Accepted for publication on Advances in Space Research http://dx.doi.org/10.1016/j.asr.2007.04.03

Chromosome Model reveals Dynamic Redistribution of DNA Damage into Nuclear Sub-domains

Several proteins involved in the response to DNA double strand breaks (DSB) form microscopically visible nuclear domains, or foci, after exposure to ionizing radiation. Radiation-induced foci (RIF) are believed to be located where DNA damage is induced. To test this assumption, we analyzed the spatial distribution of 53BP1, phosphorylated ATM and gammaH2AX RIF in cells irradiated with high linear energy transfer (LET) radiation. Since energy is randomly deposited along high-LET particle paths, RIF along these paths should also be randomly distributed. The probability to induce DSB can be derived from DNA fragment data measured experimentally by pulsed-field gel electrophoresis. We used this probability in Monte Carlo simulations to predict DSB locations in synthetic nuclei geometrically described by a complete set of human chromosomes, taking into account microscope optics from real experiments. As expected, simulations produced DNA-weighted random (Poisson) distributions. In contrast, the distributions of RIF obtained as early as 5 min after exposure to high LET (1 GeV/amu Fe) were non-random. This deviation from the expected DNA-weighted random pattern can be further characterized by relative DNA image measurements. This novel imaging approach shows that RIF were located preferentially at the interface between high and low DNA density regions, and were more frequent in regions with lower density DNA than predicted. This deviation from random behavior was more pronounced within the first 5 min following irradiation for phosphorylated ATM RIF, while gammaH2AX and 53BP1 RIF showed very pronounced deviation up to 30 min after exposure. These data suggest the existence of repair centers in mammalian epithelial cells. These centers would be nuclear sub-domains where DNA lesions would be collected for more efficient repair

Generalizability of Cardiovascular Safety Trials on SGLT2 Inhibitors to the Real World: Implications for Clinical Practice

Introduction: Following the US Food and Drug Administration (FDA) guidance on the evaluation of novel agents for the treatment of type 2 diabetes mellitus (T2DM), a number of cardiovascular outcomes safety trials (CVOTs) on sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been conducted. These trials show similarities in study design and definition of primary endpoints, but differ in their eligibility criteria. The aim of the present study was to investigate the generalizability of CVOTs on SGLT2i to Italian adults with T2DM; we estimated the proportions of this patient population who would be eligible for enrollment in EMPA-REG OUTCOME (empagliflozin), CANVAS (canagliflozin), DECLARE-TIMI 58 (dapagliflozin), and VERTIS-CV (ertugliflozin) studies. Methods: This observational, cross-sectional study was conducted in 222 Italian diabetes clinics. Data on 455,662 adult patients with T2DM seen during 2016 were analyzed against the published patient eligibility criteria for the four CVOTs. The current use of SGLT2i in potentially eligible patients was assessed. Results: Among the population identified, the proportion of patients meeting major eligibility criteria was 11.7% for EMPA-REG OUTCOME, 29.4% for CANVAS, 55.9% for DECLARE-TIMI 58, and 12.8% for VERTIS-CV. Of the patients eligible for these CVOTs, only a minority (range 4.4-6.8%) was actually prescribed an SGLT2i. Compared with patients in the CVOTs, eligible patients in the real world showed older age and longer diabetes duration, lower BMI and HbA1c levels, lower prevalence of established cardiovascular and cerebrovascular disease, and higher rates of microvascular complications and peripheral arterial disease. Conclusion: The percentage of patients potentially eligible for treatment with SGLT2i varies as a reflection of different eligibility criteria applied in the trials. A large number of patients that could benefit from SGLT2i in terms of not only cardiovascular protection but also renal protection do not receive the treatment

Biochemical Kinetics Model of DSB Repair and GammaH2AX FOCI by Non-homologous End Joining

We developed a biochemical kinetics approach to describe the repair of double strand breaks (DSB) produced by low LET radiation by modeling molecular events associated with the mechanisms of non-homologous end-joining (NHEJ). A system of coupled non-linear ordinary differential equations describes the induction of DSB and activation pathways for major NHEJ components including Ku(sub 70/80), DNA-PK(sub cs), and the Ligase IV-XRCC4 hetero-dimer. The autophosphorylation of DNA-PK(sub cs and subsequent induction of gamma-H2AX foci observed after ionizing radiation exposure were modeled. A two-step model of DNA-PK(sub cs) regulation of repair was developed with the initial step allowing access of other NHEJ components to breaks, and a second step limiting access to Ligase IV-XRCC4. Our model assumes that the transition from the first to second-step depends on DSB complexity, with a much slower-rate for complex DSB. The model faithfully reproduced several experimental data sets, including DSB rejoining as measured by pulsed-field electrophoresis (PFGE), quantification of the induction of gamma-H2AX foci, and live cell imaging of the induction of Ku(sub 70/80). Predictions are made for the behaviors of NHEJ components at low doses and dose-rates, where a steady-state is found at dose-rates of 0.1 Gy/hr or lower

Adeno-associated viral vector-mediated human vascular endothelial growth factor gene transfer stimulates angiogenesis and wound healing in the genetically diabetic mouse

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Solid State Microdosimetry With Heavy Ions for Space Applications

This work provides information pertaining to the performance of Silicon-On-Insulator (SOI) microdosimeters in heavy ion radiation fields. SOI microdosimeters have been previously tested in light ion radiation fields for both space and therapeutic applications, however their response has not been established in high energy, heavy ion radiation fields which are experienced in space. Irradiations were completed at the NASA Space Radiation Laboratory at BNL using 0.6 GeV/u Fe and 1.0 GeV/u Ti ions. Energy deposition and lineal energy spectra were obtained with this device at various depths within a Lucite phantom along the central axis of the beam. The response of which was compared with existing proportional counter data to assess the applicability of SOI microdosimeters to future deployments in space missions

Image-Based Modeling Reveals Dynamic Redistribution of DNA Damage into Nuclear Sub-Domains

Several proteins involved in the response to DNA double strand breaks (DSB) form microscopically visible nuclear domains, or foci, after exposure to ionizing radiation. Radiation-induced foci (RIF) are believed to be located where DNA damage occurs. To test this assumption, we analyzed the spatial distribution of 53BP1, phosphorylated ATM, and γH2AX RIF in cells irradiated with high linear energy transfer (LET) radiation and low LET. Since energy is randomly deposited along high-LET particle paths, RIF along these paths should also be randomly distributed. The probability to induce DSB can be derived from DNA fragment data measured experimentally by pulsed-field gel electrophoresis. We used this probability in Monte Carlo simulations to predict DSB locations in synthetic nuclei geometrically described by a complete set of human chromosomes, taking into account microscope optics from real experiments. As expected, simulations produced DNA-weighted random (Poisson) distributions. In contrast, the distributions of RIF obtained as early as 5 min after exposure to high LET (1 GeV/amu Fe) were non-random. This deviation from the expected DNA-weighted random pattern can be further characterized by “relative DNA image measurements.” This novel imaging approach shows that RIF were located preferentially at the interface between high and low DNA density regions, and were more frequent than predicted in regions with lower DNA density. The same preferential nuclear location was also measured for RIF induced by 1 Gy of low-LET radiation. This deviation from random behavior was evident only 5 min after irradiation for phosphorylated ATM RIF, while γH2AX and 53BP1 RIF showed pronounced deviations up to 30 min after exposure. These data suggest that DNA damage–induced foci are restricted to certain regions of the nucleus of human epithelial cells. It is possible that DNA lesions are collected in these nuclear sub-domains for more efficient repair