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Open Radio Access Network (RAN) is an important architecture design shift for 5G and next generation telecommunications networks. With open RAN, mobile network operators would be able to mix and match multi-vendor RAN solutions as long as the solutions comply with open standards. O-RAN Alliance is the global leader in standardizing the open RAN architecture, where RAN Intelligent Controller (RIC) is positioned centrally as the brain of a RAN to manage and optimize the RAN operations. Open-source projects play a key role in accelerating the adoption of open RAN architecture, especially the use of RIC. However, the fast pace of development and the lack of documentation in open-source projects create steep learning curve for beginners. In this paper, we first provide an overview of widely used open-source RIC projects and discuss their pros and cons. We then share our first-hand experience to use RIC in our campus 5G network that consists of commercial-grade RAN solutions. In particular, we developed a suite of three RAN control applications (i.e., energy efficiency, interference management, and predictive maintenance) on an open-source RIC, and we deploy and evaluate them on a commercial-grade 5G network in a university campus. For these RIC applications, we design and evaluate different ML models based on real-world data collected from our 5G network, which we publish together with this paper. Our experimental results show that AI-based RIC applications can achieve more than 90% of accuracy in inferring the situation of the RAN for each given task. Our energy-saving RIC application can reduce 65% of energy consumption of the RAN over a simulated period of one year. Our project also validates the feasibility to interfacing an open-source RIC with existing commercial-grade 5G solutions.

A contemporary world order is based on an increasingly complex system of interstate relations, which implies the need to thoroughly consider the international context, even when analyzing bilateral interactions. From this point of view, the concept of a ‘strategic triangle’, developed during the Cold War and applied primarily to analyze the dynamics of relationships between the USSR, the USA and the PRC, appears to have significant epistemological potential. In current conditions, it is of particular interest to use this concept to study the logic of relations in the ‘Russia–India–China’ (RIC) triangle. This research pursues two interrelated goals. On the one hand, it is aimed at identifying specific features of this new ‘strategic triangle’, its inner structure and logic of interactions between its participants. On the other hand, it assesses the applicability of the theoretical models developed during the Cold War to the relations within the framework of the RIC strategic triangle. The author examines the history, general dynamics and contemporary features of interaction within each pair of bilateral relations in this ‘triangle’. The research has confirmed the hypothesis that the relations between Russia, India, and China, indeed, form a specific subsystem of international relations, which can be described as a ‘strategic triangle’. At the same time, unlike the Sino-American-Soviet ‘strategic triangle’, it is the logic of cooperation, rather than rivalry, which generally prevails within the framework of the RIC.However, the RIC ‘triangle’ can also be described as an inherently inconsistent system. While China and Russia maintain close strategic cooperation in almost all areas, in the case of India and Russia, economic cooperation does not match the achieved level of political contacts, and Sino-Indian relations, despite the generally positive dynamics during the recent years, remain at a low level. All this points to the need to develop a new theoretical and methodological framework for analyzing trilateral relations between Russia, India and China as a special subsystem of the contemporary world politics, one that will be free from Cold War stereotypes.

Simple Summary: Allogeneic stem cell transplantation (aHSCT) is the only potentially curative treatment option for patients with high-risk myeloid malignancies. Depending on the underlying genetic risk profile, up to 50% of patients die of relapse even after aHSCT in first remission. Therefore, further improvement of conditioning regimens is an urgent medical need. Current sequential conditioning regimens combine intensive AML-like induction therapy with total body irradiation or alkylators like treosulfan or melphalan. The first and currently widely accepted prototype of this treatment strategy is the fludarabine/amsacrine/ara-C (FLAMSA) protocol, which has been modified multiple times by changing parts or adding additional cytotoxic drugs to improve clinical results. Knowing that venetoclax, an inhibitor of B-cell lymphoma-2 protein (BCL2), has synergistic effects to chemotherapy without increasing the level of non-hematologic toxicity, several German transplant centers have added venetoclax to the FLAMSA protocol as an individualized treatment approach to improve long term outcome in patients with high-risk myeloid malignancies. Up to 50% of patients with high-risk myeloid malignancies die of relapse after allogeneic stem cell transplantation. Current sequential conditioning regimens like the FLAMSA protocol combine intensive induction therapy with TBI or alkylators. Venetoclax has synergistic effects to chemotherapy. In a retrospective survey among German transplant centers, we identified 61 patients with myeloid malignancies that had received FLAMSA-based sequential conditioning with venetoclax between 2018 and 2022 as an individualized treatment approach. Sixty patients (98%) had active disease at transplant and 74% had genetic high-risk features. Patients received allografts from matched unrelated, matched related, or mismatched donors. Tumor lysis syndrome occurred in two patients but no significant non-hematologic toxicity related to venetoclax was observed. On day +30, 55 patients (90%) were in complete remission. Acute GvHD II°–IV° occurred in 17 (28%) and moderate/severe chronic GvHD in 7 patients (12%). Event-free survival and overall survival were 64% and 80% at 1 year as well as 57% and 75% at 2 years, respectively. The off-label combination of sequential FLAMSA-RIC with venetoclax appears to be safe and highly effective. To further validate these insights and enhance the idea of smart conditioning, a controlled prospective clinical trial was initiated in July 2023. [ABSTRACT FROM AUTHOR]

Modern mobile networks exhibit a complex heterogeneous structure. To enhance the Quality of Service (QoS) in these networks, intelligent control mechanisms should be implemented. These functions are based on the processing of large amounts of data and feature extraction. One such feature is information about user mobility. However, directly determining user mobility remains challenging. To address this issue, this study proposes an approach based on multi-linear data processing. The user mobility is proposed to determine, using the multi-linear data, about the changing of the Signal-to-Interference-plus-Noise-Ratio (SINR). SINR varies individually for each user over time, relative to the network's base stations. It is natural to represent these data as a tensor. A tensor-based preprocessing step employing Canonical Polyadic Decomposition (CPD) is proposed to extract user mobility information and reduce the data volume. In the next step, using the DBSCAN algorithm, users are clustered according to their mobility patterns. Subsequently, users are clustered based on their mobility patterns using the DBSCAN algorithm. The proposed approach is evaluated utilizing data from Network Simulator 3 (NS-3), which simulates a portion of the mobile network. The results of processing these data using the proposed method demonstrate superior performance in determining user mobility. [ABSTRACT FROM AUTHOR]

RAS GTPases are highly conserved proteins involved in the regulation of mitogenic signaling. We have previously described a novel Cullin 3 RING E3 ubiquitin ligase complex formed by the substrate adaptor protein LZTR1 that binds, ubiquitinates, and promotes proteasomal degradation of the RAS GTPase RIT1. In addition, others have described that this complex is also responsible for the ubiquitination of classical RAS GTPases. Here, we have analyzed the phenotypes of Lztr1 loss-of-function mutants in both fruit flies and mice and have demonstrated a biochemical preference for their RIT1 orthologs. Moreover, we show that Lztr1 is haplosufficient in mice and that embryonic lethality of the homozygous null allele can be rescued by deletion of Rit1. Overall, our results indicate that, in model organisms, RIT1 orthologs are the preferred substrates of LZTR1.

India and Russia share a vision of a multipolar world, which is reflected in their cooperation within international organizations and fora such as the United Nations, Russia-India-China (RIC), BRICS and the Shanghai Cooperation Organization (SCO). India has shown greater enthusiasm towards RIC and BRICS than SCO due to its non-founder status and concerns over the group's creation to further China's regional agenda. The expansion of BRICS and a potential free trade agreement pose challenges to India-Russia relations and require more bilateral engagement. Russia should realistically assess the benefits of endorsing China's Belt and Road Initiative while also considering the potential of the International North-South Transport Corridor (INSTC) to access West Asian and South Asian markets and mitigate the impact of Western sanctions on the Russian economy. India and Russia must collaborate to build regional consensus on the INSTC through RIC, BRICS, and SCO platforms. Despite Russia's growing proximity to China, Moscow has not compromised its support for New Delhi on issues such as Kashmir, terrorism, membership in the Nuclear Suppliers Group (NSG), and the United Nations Security Council. In contrast, China continues to question and oppose India on these matters. Similarly, India has maintained friendly ties with Russia and has not succumbed to Western pressure. Cooperation between India and Russia in international organizations has further strengthened their bilateral ties, and they must continue to work together to maintain a multipolar Eurasia, as neither can achieve this goal alone.

Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR], .74; 95% confidence interval [CI], .62 to .88; P < .001) but significantly greater relapse risk (HR, 1.54; 95% CI, 1.35 to 1.76; P < .001) and thus inferior disease-free survival (DFS) (HR, 1.19; 95% CI, 1.07 to 1.33; P = .001). In the high/very high-risk DRI cohort, RIC was associated with marginally lower NRM (HR, .83; 95% CI, .68 to 1.00; P = .051) and significantly higher relapse risk (HR, 1.23; 95% CI, 1.08 to 1.41; P = .002), leading to similar DFS using either RIC or MAC. These data support MAC over RIC as the preferred conditioning intensity for patients with AML/MDS with low/intermediate-risk DRI, but with a similar benefit as RIC in high/very high-risk DRI. Novel MAC regimens with less toxicity could benefit all patients, but more potent antineoplastic approaches are needed for the high/very-high risk DRI group.

This article addresses the issue of implementing and assessing the readiness of territorial and economic systems for digital innovations in the energy industry. To achieve the goal of this research, qualitative and quantitative methods were used, including systemic and comparative analyses, a balanced scorecard (BSC), and statistical data collection and processing methods. The study resulted in a list of indicators for monitoring the readiness of the energy sector for digitization, based on which a balanced scorecard reflecting the readiness of the energy industry in countries and regional industrial complexes (RICs) was developed. A strategic map for assessing the level of readiness of the power industry for digitisation in countries and RICs was constructed using the indicator pool. The uniqueness and novelty of this study lie in the adaptation of a balanced scorecard system, aligned with a country's or RIC's development strategy, to determine indicators for assessing the readiness level of the considered entity for digitising the power industry. The authors establish an approach to the overall assessment and subsequent monitoring of the energy industry's readiness for digitisation in countries worldwide and RICs. [ABSTRACT FROM AUTHOR]

Rapid infusion catheters (RICs) allow expedient conversion of peripheral intravenous (PIV) catheters to peripheral sheaths; however, little is known about potential complications. In this case, a 64-year-old male polytrauma patient had a 20-gauge PIV catheter in the right cephalic vein upsized to an 8.5 French (Fr) RIC without incident during an arrest with pulseless electrical activity (PEA). On RIC post-placement day two, the patient developed edema and ecchymosis extending from the right dorsal mid-hand to the antecubital fossa, just distal to the RIC insertion point. Compartments were soft; the volar surface (including an arterial line location), fingers, and upper arm were normal. The RIC flushed and returned blood appropriately. Ultrasound revealed a noncompressible cephalic vein either related to the catheter or thrombosis, and imaging of the hand showed an ulnar styloid fracture and a minimally displaced triquetral fracture. The RIC was removed immediately. Over the next week, the areas of ecchymosis developed bullae and then sloughed, leaving open wounds extending into the dermis. The patient later expired from unrelated causes. The area and timing of the skin necrosis were highly suspicious for a catheter-associated complication, despite the presence of the arterial line and small distal fractures. The necrosis was potentially due to thrombosis of the superficial venous outflow system, leading to congestion and skin compromise, but we found no similar reports. Alternatively, the catheter may have ruptured the vein and caused a gravity-dependent ecchymosis, but the volar surface was not impacted, and the catheter was functioning properly. The RIC may also have encroached on the arterial space, decreasing flow, but we would have expected distal hand changes. The only published reports we could find on RIC complications involved a lost guide wire, fragmentation of a catheter during placement, and a case of compartment syndrome, raising the question of whether skin necrosis is truly a rare event or simply underreported with the RIC. Although the exact causal relationship remains unknown in our case, RICs should be removed as soon as possible after immediate stabilization.

Background: Initiating newly diagnosed people living with human immunodeficiency virus (HIV) onto antiretroviral treatment (ART) and retaining patients on treatment are vital to South Africa's ART programme. In 2020, coronavirus disease 2019 (COVID-19) and its accompanying containment (lockdown) measures presented unprecedented challenges to achieving these objectives. Aim: This study describes the impact of COVID-19 and related restrictions on district-level numbers of newly diagnosed people living with HIV and defaulting ART patients. Setting: Buffalo City Metropolitan Municipality (BCMM) in the Eastern Cape of South Africa. Methods: Mixed-methods approach: Monthly aggregated electronic patient data (newly initiated and restarted on ART) from 113 public healthcare (PHC) facilities were analysed (December 2019 to November 2020) across varying levels of COVID-19 lockdown regulation periods; telephonic in-depth interviews at 10 rural BCMM PHC facilities were conducted with facility staff, community health workers (CHWs) and intervention personnel. Results: The number of newly initiated ART patients decreased dramatically compared with pre-COVID-19 levels. The overall number of restarted ART patients increased in response to fears of co-infection with COVID-19. Facility-level communications and community outreach promoting HIV testing and treatment were disrupted. Novel approaches to providing services to ART patients were developed. Conclusion: Programmes for identifying undiagnosed people living with HIV and services aimed at retaining ART patients in care were profoundly impacted by COVID-19. The value of CHWs was highlighted, as were communication innovations. Contribution: This study describes the impact of COVID-19 and related regulations on HIV testing, ART initiation and adherence to treatment in a District of the Eastern Cape of South Africa. [ABSTRACT FROM AUTHOR]

Modern mobile networks exhibit a complex heterogeneous structure. To enhance the Quality of Service (QoS) in these networks, intelligent control mechanisms should be implemented. These functions are based on the processing of large amounts of data and feature extraction. One such feature is information about user mobility. However, directly determining user mobility remains challenging. To address this issue, this study proposes an approach based on multi-linear data processing. The user mobility is proposed to determine, using the multi-linear data, about the changing of the Signal-to-Interference-plus-Noise-Ratio (SINR). SINR varies individually for each user over time, relative to the network’s base stations. It is natural to represent these data as a tensor. A tensor-based preprocessing step employing Canonical Polyadic Decomposition (CPD) is proposed to extract user mobility information and reduce the data volume. In the next step, using the DBSCAN algorithm, users are clustered according to their mobility patterns. Subsequently, users are clustered based on their mobility patterns using the DBSCAN algorithm. The proposed approach is evaluated utilizing data from Network Simulator 3 (NS-3), which simulates a portion of the mobile network. The results of processing these data using the proposed method demonstrate superior performance in determining user mobility.

Background: Initiating newly diagnosed people living with human immunodeficiency virus (HIV) onto antiretroviral treatment (ART) and retaining patients on treatment are vital to South Africa’s ART programme. In 2020, coronavirus disease 2019 (COVID-19) and its accompanying containment (lockdown) measures presented unprecedented challenges to achieving these objectives. Aim: This study describes the impact of COVID-19 and related restrictions on district-level numbers of newly diagnosed people living with HIV and defaulting ART patients. Setting: Buffalo City Metropolitan Municipality (BCMM) in the Eastern Cape of South Africa. Methods: Mixed-methods approach: Monthly aggregated electronic patient data (newly initiated and restarted on ART) from 113 public healthcare (PHC) facilities were analysed (December 2019 to November 2020) across varying levels of COVID-19 lockdown regulation periods; telephonic in-depth interviews at 10 rural BCMM PHC facilities were conducted with facility staff, community health workers (CHWs) and intervention personnel. Results: The number of newly initiated ART patients decreased dramatically compared with pre-COVID-19 levels. The overall number of restarted ART patients increased in response to fears of co-infection with COVID-19. Facility-level communications and community outreach promoting HIV testing and treatment were disrupted. Novel approaches to providing services to ART patients were developed. Conclusion: Programmes for identifying undiagnosed people living with HIV and services aimed at retaining ART patients in care were profoundly impacted by COVID-19. The value of CHWs was highlighted, as were communication innovations. Contribution: This study describes the impact of COVID-19 and related regulations on HIV testing, ART initiation and adherence to treatment in a District of the Eastern Cape of South Africa.

The network of the fifth-generation mobile-communications-system era must be able to support many and varied applications, which means ever increasing complexity. It will therefore not be easy to control and optimize network operations by manual means as done in the past. NTT DOCOMO is developing radio access network (RAN) Intelligent Controller (RIC) technology now being standardized at the O-RAN ALLIANCE with the aim of achieving more autonomous and automatic RAN operations, that is, intelligent RAN, by using machine learning and other forms of artificial intelligence, big data, etc. This article describes the state of RIC standardization at the O-RAN ALLIANCE and presents NTT DOCOMO's approach to use cases and a roadmap toward intelligent RAN. [ABSTRACT FROM AUTHOR]

The potential modifiable factors for remote ischemic conditioning (RIC) in reducing contrast-associated acute kidney injury (CA-AKI) in patients with acute myocardial infarction (AMI) have not been investigated. The aim of this meta-regression was to address these issues.We searched Pubmed, Embase and the Cochrane Library database for published randomized controlled trials (RCTs) with registration number CRD42020155532. Nine RCTs comprising of 1540 subjects were included in our meta-analysis. Compared with control group, RIC was associated with reduced incidence of CA-AKI [(9 studies, 1540 subjects, relative risk (RR) 0.51, 95% confidence intervals (CI) 0.35 to 0.76, p = 0.000, I2 = 52%, p for heterogeneity 0.04)] and major adverse cardiovascular events (MACE) (5 studies, 1078 subjects, RR 0.52, 95% CI 0.38 to 0.73, p = 0.000, I2 = 9%, p for heterogeneity 0.36) for AMI. In addition, both meta-regression and subgroup analyses have shown that RIC was more effective in the hypertensive patients in reducing CA-AKI for AMI (regression coefficient = -0.05, p = 0.021; for subgroup with more hypertensive patients: RR 0.36, 95% CI 0.25 to 0.52 vs the one with less hypertensive patients: RR 0.72, 95% CI (0.40 to 1.30, p for subgroup difference 0.008). Subsequent trial sequential analysis confirmed the effect of RIC in both CA-AKI and MACE. RIC is an effective strategy in reducing CA-AKI and MACE in patients with AMI, especially for patients with hypertension. [ABSTRACT FROM AUTHOR]

Introduction: The Italian Radical Cystectomy Registry (RIC) is an observational prospective study aiming to understand clinical variables and patient characteristics associated with short- and long-term outcomes among bladder cancer (BC) patients undergoing radical cystectomy (RC). Moreover, it compares the effectiveness of three RC techniques - open, robotic, and laparoscopic. Methods: From 2017 to 2020, 1400 patients were enrolled at one of the 28 centers across Italy. Patient characteristics, as well as preoperative, postoperative, and follow-up (3, 6, 12, and 24 months) clinical variables and outcomes were collected. Results: Preoperatively, it was found that patients undergoing robotic procedures were younger (p<.001) and more likely to have undergone preoperative neoadjuvant chemotherapy (p<.001) and BCG instillation (p<.001). Hypertension was the most common comorbidity among all patients (55%), and overall, patients undergoing open and laparoscopic RC had a higher Charlson Comorbidities Index (CCI) compared to robotic RC (p<.001). Finally, laparoscopic patients had a lower G-stage classification (p=.003) and open patients had a higher ASA score (p<.001). Conclusion: The present study summarizes the characteristic of patients included in the RIC. Future results will provide invaluable information about outcomes among BC patients undergoing RC. This will inform physicians about the best techniques and course of care based on patient clinical factors and characteristics. [ABSTRACT FROM AUTHOR]

IntroductionThe Italian Radical Cystectomy Registry (RIC) is an observational prospective study aiming to understand clinical variables and patient characteristics associated with short- and long-term outcomes among bladder cancer (BC) patients undergoing radical cystectomy (RC). Moreover, it compares the effectiveness of three RC techniques - open, robotic, and laparoscopic.MethodsFrom 2017 to 2020, 1400 patients were enrolled at one of the 28 centers across Italy. Patient characteristics, as well as preoperative, postoperative, and follow-up (3, 6, 12, and 24 months) clinical variables and outcomes were collected.ResultsPreoperatively, it was found that patients undergoing robotic procedures were younger (p

RAS GTPases are highly conserved proteins involved in the regulation of mitogenic signaling. We have previously described a novel Cullin 3 RING E3 ubiquitin ligase complex formed by the substrate adaptor protein LZTR1 that binds, ubiquitinates, and promotes proteasomal degradation of the RAS GTPase RIT1. In addition, others have described that this complex is also responsible for the ubiquitination of classical RAS GTPases. Here, we have analyzed the phenotypes of Lztr1 loss-of-function mutants in both fruit flies and mice and have demonstrated a biochemical preference for their RIT1 orthologs. Moreover, we show that Lztr1 is haplosufficient in mice and that embryonic lethality of the homozygous null allele can be rescued by deletion of Rit1. Overall, our results indicate that, in model organisms, RIT1 orthologs are the preferred substrates of LZTR1.

An important and not often addressed topic - considering the issues opened by cross-disciplinary projects - is the shared control of authority records, or better authority metadata, extended to other documentary and cultural heritage sciences. This paper will examine the potential opened by multi-dimensional and networked logics in the representation of entities in the form of data towards which the document communities are converging. This approach is even more valid if we consider the users' point of view, presently forced to jump from one information environment to another, and confront different names, forms and attributes for the same entities. The core entities to work on are persons, corporate bodies, places, chronological contexts, events, qualifying their relationships. After a brief resume of archival description's peculiarity, the paper highlights the updated standards available, mostly IFLA-LRM and RiC, precious documents to start from and stimulate an active collaboration. To facilitate the sharing, control, and enrichment of authority data in the form of RDF assertions, librarians and archivists may follow several pathways: matching the existing conceptual models, converging on a shared data playground like Wikidata, and developing foundational meta-ontology. [ABSTRACT FROM AUTHOR]

En este artículo se presenta el modelo conceptual de la norma Records in Contexts (RiC-CM) y la ontología de esta norma (RiC-O), propuestos por el Consejo Internacional de Archivos para el dominio archivístico. Ambas propuestas se despliegan y analizan, y se complementan con algunos comentarios de referentes del área, con el objetivo contribuir a la comprensión de la estructura y al fundamento de RiC y proporcionar un insumo para su evaluación y las dificultades de su implantación práctica. La integración de los archivos digitales con dominios cercanos, como las bibliotecas, galerías y museos, así como objetos de otros dominios con los que tradicionalmente no se relacionaban, incorpora la perspectiva multidimensional y es una oportunidad para desarrollar el ámbito archivístico. Las tecnologías de la web semántica, ontologías, datos enlazados, RDF, SPARQL son un actor infraestructural para construir esa integración y dar cuenta de un cambio en el mundo archivístico insertándolo en la web. La implementación de esta propuesta es un avance hacia la integración, pero plantea desafíos por resolver.

Using haploidentical donors for allogeneic hematopoietic cell transplantation (HCT) broadens transplant accessibility to a growing number of patients with hematologic disorders. Moreover, haploidentical HCT with post-transplant cyclophosphamide (PTCy) has become widespread practice due to accumulating evidence demonstrating favorable rates of survival and graft-versus-host disease (GvHD). Most studies comparing outcomes by donor sources have been confounded by variability in conditioning regimens, graft type (peripheral blood [PB] or bone marrow), and post-transplant GvHD prophylaxis (PTCy or non-PTCy), making it difficult to define the effect of donor source on outcomes. Levine Cancer Institute started a transplant and cellular therapy program in 2014, with both haploidentical and matched related donor (MRD) transplants initially performed using a uniform reduced-intensity conditioning (RIC) regimen, PB grafts, and PTCy-based GvHD prophylaxis. This retrospective observational study was conducted to compare the clinical outcomes associated with RIC haploidentical HCT and MRD HCT in patients receiving identical conditioning regimens, graft types, and supportive care. Our transplant database was queried to evaluate demographic characteristics, clinical features, and outcomes of RIC HCT for consecutive patients with hematologic malignancies who received haploidentical or MRD grafts between March 2014 and December 2017. An MRD was the preferred donor source; when unavailable, a haploidentical donor was used. Sixty-seven patients underwent haploidentical HCT and 25 MRD HCT. Overall, characteristics of transplant recipients were similar for the haploidentical and MRD groups; however, haploidentical donors were younger than MRDs (median 36 yr versus 57 yr, P < .0001). Results of univariable analysis showed similar overall survival (OS) for haploidentical and MRD HCT (hazard ratio [HR], 1.15; 95% CI, 0.61 to 2.15; P = .669). One-year, 1-yr, and 5-yr OS were 80.2%, 54.7%, and 41.2% for haploidentical HCT and 76.0%, 55.7%, and 51.1% for MRD HCT, respectively. With a median follow-up of 81.90 months, results of multivariable analysis revealed that donor source (haploidentical versus MRD) was not significantly associated with OS (HR, 0.97; 95% CI, 0.51 to 1.87; P = .933), relapse-free survival (HR, 0.75; 95% CI, 0.42 to 1.35; P = .337), cumulative incidence of relapse (HR, 0.81; 95% CI, 0.39 to 1.70; P = .579), or non-relapse mortality (HR, 1.12; 95% CI, 0.40 to 3.14; P = .827). Cumulative incidences of acute GvHD (aGvHD) and chronic GvHD (cGvHD) were not significantly different for haploidentical and MRD HCT (grades II to IV aGvHD: HR, 1.78; 95% CI, 0.72 to 4.37; P = .210; grades III to IV aGvHD: HR, 2.84; 95% CI, 0.34 to 23.63; P = .335; cGvHD: HR, 1.00; 95% CI 0.36 to 2.76; P = .995). With care that was homogenous in terms of conditioning regimens, graft type, GvHD prophylaxis, and supportive care, 92 patients who were biologically randomized to either haploidentical HCT or MRD HCT after RIC with PTCy had comparable outcomes., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: Remote ischemic preconditioning (RIPC) is a phenomenon in which the induction of shortened periods of ischemia prior to surgical procedures within a distant tissue preserves other tissues or organs of concern, such as the liver or kidney in transplant surgery, in the event of prolonged ischemic insults. The authors aim to evaluate the effectiveness of RIPC in patients undergoing transplant surgery, specifically kidney and liver transplants., Materials and Methods: PubMed, Embase, and Scopus were searched until 19 December 2023 for trials evaluating RIPC in patients undergoing transplant surgery. A total of 9364 search articles were obtained, which yielded 10 eligible studies. Data analysis was done using RevMan 5.4 software. The risk of bias was done using Cochrane risk of bias tool., Results and Discussion: For graft rejection, the study observed a relative risk of 0.99 (95% CI, 0.49-1.98, P =0.97) from 5 trials, indicating no significant effect of RIPC on graft survival in both kidney and liver transplants. The length of hospital stay also showed no significant decrease for those undergoing RIPC, with mean difference (MD) of -0.58 (95% CI, -1.38 to 0.23, P =0.16). GFR at 1-year post-kidney transplant did not significantly change in the RIPC group compared to controls, as evidenced by an MD of -0.13 (95% CI, -3.79 to 3.54, P =0.95). These results collectively suggest that RIPC may not be effective in reducing patient, or graft, outcomes., Competing Interests: The authors involved in this review certify that they have no conflict of interest, affiliations with or involvement in any organization or entity with any financial interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To assess the efficacy of remote ischemic conditioning (RIC) in patients with ischemic stroke within 9 h of onset, that are not candidates for recanalization therapies. Sample Size Estimates: A sample size of 80 patients (40 in each arm) should yield 80% power to detect a 20% difference in early neurological improvement at 72 h at p = 0.05, two sided. Methods and Design: TRICS-9 is a phase II, multicenter, controlled, block randomized, open-label, interventional clinical trial. Patients recruited in Italian academic hospitals will be randomized 1:1 to either RIC plus standard medical therapy or standard medical therapy alone. After randomization, RIC will be applied manually by four alternating cycles of inflation/deflation 5 min each, using a blood pressure cuff around the non-paretic arm. Study Outcomes: The primary efficacy outcome is early neurological improvement, defined as the percent change in the National Institute of Health Stroke Scale (NIHSS) at 72 h in each arm. Secondary outcomes include early neurologic improvement at 24 and 48 h, disability at 3 months, rate of symptomatic intracerebral hemorrhage, feasibility (proportion of patients completing RIC), tolerability after RIC and at 72 h, blood levels of HIF-1α, and HSP27 at 24 h and 72 h. Discussion/Conclusion: RIC in combination with recanalization therapies appears to add no clinical benefit to patients, but whether it is beneficial to those that are not candidates for recanalization therapies is still to be demonstrated. TRICS-9 has been developed to elucidate this issue. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04400981. [ABSTRACT FROM AUTHOR]

Background and purposeRemote ischemic conditioning (RIC) is a phenomenon in which short periods of non-fatal ischemia in one tissue confers protection to distant tissues. Here we performed a longitudinal human pilot study in patients with aneurysmal subarachnoid hemorrhage (aSAH) undergoing RIC by limb ischemia to compare changes in DNA methylation and transcriptome profiles before and after RIC.MethodsThirteen patients underwent 4 RIC sessions over 2–12 days after rupture of an intracranial aneurysm. We analyzed whole blood transcriptomes using RNA sequencing and genome-wide DNA methylomes using reduced representation bisulfite sequencing, both before and after RIC. We tested differential expression (DE) and differential methylation (DM) using an intra-individual paired study design, and then overlapped the DE and DM results for analyses of functional categories and protein-protein interactions.ResultsWe observed 164 DE genes and 3,493 DM CpG sites after RIC, of which 204 CpG sites overlapped with 103 genes, enriched for pathways of cell cycle (P

Aim: To assess the efficacy of remote ischemic conditioning (RIC) in patients with ischemic stroke within 9 h of onset, that are not candidates for recanalization therapies.Sample Size Estimates: A sample size of 80 patients (40 in each arm) should yield 80% power to detect a 20% difference in early neurological improvement at 72 h at p = 0.05, two sided.Methods and Design: TRICS-9 is a phase II, multicenter, controlled, block randomized, open-label, interventional clinical trial. Patients recruited in Italian academic hospitals will be randomized 1:1 to either RIC plus standard medical therapy or standard medical therapy alone. After randomization, RIC will be applied manually by four alternating cycles of inflation/deflation 5 min each, using a blood pressure cuff around the non-paretic arm.Study Outcomes: The primary efficacy outcome is early neurological improvement, defined as the percent change in the National Institute of Health Stroke Scale (NIHSS) at 72 h in each arm. Secondary outcomes include early neurologic improvement at 24 and 48 h, disability at 3 months, rate of symptomatic intracerebral hemorrhage, feasibility (proportion of patients completing RIC), tolerability after RIC and at 72 h, blood levels of HIF-1α, and HSP27 at 24 h and 72 h.Discussion/Conclusion: RIC in combination with recanalization therapies appears to add no clinical benefit to patients, but whether it is beneficial to those that are not candidates for recanalization therapies is still to be demonstrated. TRICS-9 has been developed to elucidate this issue.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT04400981.

The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives.

Background: Previous work has evaluated the effect of remote ischaemic conditioning (RIC) in a number of clinical conditions (e.g. cardiac surgery and acute kidney injury), but only one analysis has examined blood pressure (BP) changes. While individual studies have reported the effects of acute bouts and repeated RIC exposure on resting BP, efficacy is equivocal. We conducted a systematic review and meta-analysis to evaluate the effects of acute and repeat RIC on BP. Methods: A systematic search was performed using PubMed, Web of Science, EMBASE, and Cochrane Library of Controlled Trials up until October 31, 2020. Additionally, manual searches of reference lists were performed. Studies that compared BP responses after exposing participants to either an acute bout or repeated cycles of RIC with a minimum one-week intervention period were considered. Results: Eighteen studies were included in this systematic review, ten examined acute effects while eight investigated repeat effects of RIC. Mean differences (MD) for outcome measures from acute RIC studies were: systolic BP 0.18 mmHg (95%CI -0.95, 1.31; p = 0.76), diastolic BP -0.43 mmHg (95%CI -2.36, 1.50; p = 0.66), MAP -1.73 mmHg (95%CI -3.11, −0.34; p = 0.01) and HR -1.15 bpm (95%CI -2.92, 0.62; p = 0.20). Only MAP was significantly reduced. Repeat RIC exposure showed non-significant change in systolic BP -3.23 mmHg (95%CI -6.57, 0.11; p = 0.06) and HR -0.16 bpm (95%CI -7.08, 6.77; p = 0.96) while diastolic BP -2.94 mmHg (95%CI -4.08, −1.79; p

The use of reduced-intensity conditioning (RIC) regimens has increased in an effort to minimize hematopoietic stem cell transplantation (HCT) end-organ toxicity, including gonadal toxicity. We aimed to describe the incidence of fertility potential and gonadal function impairment in adolescent and young adult survivors of HCT and to identify risk factors (including conditioning intensity) for impairment. We performed a multi-institutional, international retrospective cohort study of patients age 10 to 40 years who underwent first allogeneic HCT before December 1, 2019, and who were alive, in remission, and available for follow-up at 1 to 2 years post-HCT. For females, an AMH level of ≥.5 ng/mL defined preserved fertility potential; an AMH level of ≥.03 ng/mL was considered detectable. Gonadal failure was defined for females as an elevated follicle-stimulating hormone (FSH) level >30 mIU/mL with an estradiol (E2) level <17 pg/mL or current use of hormone replacement therapy (regardless of specific indication or intent). For males, gonadal failure was defined as an FSH level >10.4 mIU/mL or current use of hormone replacement therapy. A total of 326 patients (147 females) were available for analysis from 17 programs (13 pediatric, 4 adult). At 1 to 2 years post-HCT, 114 females (77.6%) had available FSH and E2 levels and 71 (48.3%) had available AMH levels. FSH levels were reported for 125 males (69.8%). Nearly all female HCT recipients had very low levels of AMH. One of 45 (2.2%) recipients of myeloablative conditioning (MAC) and four of 26 (15.4%) recipients of reduced-intensity conditioning (RIC) (P = .06) had an AMH ≥.5 ng/m, and 8 of 45 MAC recipients (17.8%) and 12 of 26 RIC recipients (46.2%) (P = .015) had a detectable AMH level. Total body irradiation (TBI) dose and cyclophosphamide equivalent dose (CED) were not associated with detectable AMH. The incidence of female gonadal hormone failure was 55.3%. In univariate analysis, older age at HCT was associated with greater likelihood of gonadal failure (median age, 17.6 versus 13.9; P < .0001), whereas conditioning intensity (RIC versus MAC), TBI, chronic graft-versus-host disease requiring systemic therapy, and CED were not significantly associated with gonadal function. In multivariable analysis, age remained statistically significant (odds ratio [OR]. 1.11; 95% confidence interval [CI], 1.03 to 1.22) for each year increase; P = .012), Forty-four percent of the males had gonadal failure. In univariate analysis, older age (median, 16.2 years versus 14.4 years; P = .0005) and TBI dose (P = .002) were both associated with gonadal failure, whereas conditioning intensity (RIC versus MAC; P = .06) and CED (P = .07) were not statistically significant. In multivariable analysis, age (OR, 1.16; 95% CI, 1.06-1.27 for each year increase; P = .0016) and TBI ≥600 cGy (OR, 6.23; 95% CI, 2.21 to 19.15; P = .0008) remained significantly associated with gonadal failure. Our data indicate that RIC does not significantly mitigate the risk for gonadal failure in females or males. Age at HCT and (specifically in males) TBI use seem to be independent predictors of post-transplantation gonadal function and fertility status. All patients should receive pre-HCT infertility counseling and be offered appropriate fertility preservation options and be screened post-HCT for gonadal failure., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Insights are developed into grouping PMU signals for guaranteeing data recovery under sparse corruption. Analytical relations are derived to express the denseness of the subspace spanned by a measurement window in terms of the modal observabilities of its constituent signals. It is shown that grouping signals by minimizing variation in phase angles and amplitudes of observabilities for each poorly-damped mode minimizes the numerical-rank of the measurement window, enhances denseness of the subspace, and helps in attaining the sufficiency condition guaranteeing exact recovery using Robust Principal Component Analysis-based signal reconstruction methods. These insights are structured into lemmas and propositions for signal selection and are validated on synthetic data from IEEE test systems, as well as field PMU data from a US utility. [ABSTRACT FROM AUTHOR]

• Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is rare after reduced-intensity conditioning (RIC) transplantation with a cumulative incidence of 1.6% in our large modern cohort. • VOD/SOS continues to be associated with a high nonrelapse mortality (NRM); in our cohort, day 100 NRM was 23% in patients with VOD/SOS compared with 6.4% in patients without VOD/SOS. • VOD/SOS in RIC patients often does not meet classical Baltimore/Seattle criteria and has a later onset, a lower peak bilirubin, and better survival than VOD/SOS in patients with myeloablative conditioning. • VOD/SOS after RIC is strongly associated with higher-dose busulfan (6.4 versus 3.2 mg/kg) in the RIC regimen and use of sirolimus in the graft-versus-host disease prophylaxis regimen. fludarabine with intravenous busulfan at doses of 3.2 mg/kg (Flu/Bu1) or 6.4 mg/kg (Flu/Bu2). Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a serious complication of hematopoietic stem cell transplantation (HCT) that is felt to be triggered, at least in part, by damage to the liver sinusoidal endothelium from cytotoxic conditioning regimens. Accordingly, the incidence of VOD/SOS after reduced-intensity conditioning (RIC) HCT is low compared with myeloablative transplantation, and the natural history, risk factors, and outcomes of VOD/SOS after RIC have not been well characterized. We retrospectively reviewed 1583 consecutive patients receiving RIC HCT at the Dana-Farber Cancer Institute between 2007 and 2017 and ascertained 26 cases of VOD/SOS. The median day of VOD/SOS onset was 26 days (range, 5 to 48) and the cumulative incidence at day 50 was 1.6% (95% confidence interval [CI], 1.1% to 2.4%). Day 100 nonrelapse mortality rate was 23% in the VOD/SOS cohort compared with 6.4% in patients without VOD/SOS (P =.006). Cumulative incidence of VOD/SOS at day 50 was 3.1% after RIC regimen with Flu/Bu2 ± ATG (fludarabine with two doses of busulfan, total dose 6.4 mg/kg, with or without anti-thymocyte globulin), compared with 0.15% after Flu/Bu1 ± ATG (fludarabine with single busulfan dose 3.2 mg/kg, with or without anti-thymocyte globulin) (P =.0002); the incidence rate was 2.1% after RIC HCT with sirolimus-containing graft-versus-host disease prophylaxis, compared with 0.8% for RIC without sirolimus (P =.06). Significant risk factors identified in multivariable analysis for the development of VOD/SOS were sirolimus use (hazard ratio [HR], 5.1; 95% CI, 1.8 to 14.2; P =.002) and RIC regimen with Flu/Bu2 ± ATG (HR, 34; 95% CI, 4.5 to 252; P <.001) or other (HR, 32; 95% CI, 3.9 to 257; P =.001) compared with Flu/Bu1 ± ATG. Rising serum tacrolimus or sirolimus levels, new acute kidney injury, and increasing platelet transfusion requirements were significant early predictors of onset in the week preceding prior VOD/SOS diagnosis. When compared with a previously published cohort of 76 patients with VOD/SOS who developed VOD/SOS after myeloablative HCT in the same time period, VOD/SOS after RIC occurred later and was associated with a lower peak bilirubin level and better overall survival. The variability in presenting features for RIC VOD/SOS highlights the importance of maintaining a high index of suspicion for this entity in RIC HCT. [ABSTRACT FROM AUTHOR]

A análise da fragilidade e da dicotomia de uma nova coalizão da governança mundial, denominada BRICS, identifica três principais fatores de divergência no seu âmbito - a diferença identitária e as distinções de interesses comuns dos dois subgrupos - o IBSA e os RICs; focos de conflitos latentes entre a China e a Índia e a diferença entre a China e os restantes; o contraste entre os interesses nacionais e comunitários, como uma eventual linha divisória na coalizão, se e quando os objetivos comuns do grupo forem alcançados. A estratégia de ser optada pelo Brasil neste contexto ambíguo e incerto apresenta a complexidade de decisão e das táticas diplomáticas no âmbito dos BRICS com vistas a um surgimento das tendências de divisão e de interesses conflitantes.

• The type of donor (sibling versus MUD versus haplo) is not associated with outcomes after a clofarabine-based RIC regimen for myeloid malignancies. • Our data suggest that haploidentical donors are an acceptable alternative for patients receiving a clofarabine-based RIC PBSC allograft for myeloid malignancies who lack an MSD or a MUD. • Myelodysplastic syndrome (versus AML), high disease risk index, and older donor (≥50 years) were associated with lower OS and DFS. Clofarabine-based reduced-intensity conditioning (RIC) regimens are well-established schedules for allograft in patients with myeloid malignancies. A retrospective study was conducted including all adults allografted in our department with such a regimen and disease with the aim to assess whether or not the donor type (matched sibling [MSD], matched unrelated [MUD], or haploidentical [haplo]) impacted outcomes. Between October 2009 and February 2018, 118 patients met the inclusion criteria. Thirty-six, 55, and 27 patients received a graft from an MSD, MUD, or haplo donor, respectively. Peripheral blood stem cells (PBSCs) were the source of graft for all patients. The median age of the entire cohort was 62 years (range, 20 to 73), and the median follow-up was 31 months (range, 4.5 to 106). All patients engrafted except 1 haplo recipient. Neutrophils (>.5 × 109/L) and platelets (50 × 109/L) recoveries were significantly delayed in the haplo group (P =.0003 and P <.0001) compared with MSD and MUD. Acute grades II to IV or III to IV graft-versus-host disease (GVHD) incidences were similar between the 3 groups as well as the incidence of moderate or severe chronic GVHD. Also, similar 2-year overall survival (OS; 64.7% versus 73.9% versus 60.2%, P =.39), disease-free survival (DFS; 57.7% versus 70.9% versus and 53.6%, P =.1), and GVHD relapse-free survival (37.9% versus 54.3% versus 38.9%, P =.23) were observed between MSD versus MUD versus haplo groups. The same was true when considering only acute myeloid leukemia (AML) cases. In multivariate analysis the type of donor remained independent of outcomes in this series, whereas myelodysplastic syndrome (versus AML), high disease risk index, and older donor (≥50 years) were associated with lower OS and DFS. These data suggest that haplo donors are an acceptable alternative for patients receiving a clofarabine-based RIC PBSC allograft for myeloid malignancies who lack an MSD or a MUD. [ABSTRACT FROM AUTHOR]

Reduced-intensity conditioning (RIC) and T cell depletion (TCD) through CD34 + cell selection without the use of post-transplantation immunosuppression are 2 strategies used to reduce nonrelapse mortality (NRM) in older patients after allogeneic hematopoietic cell transplantation (allo-HCT). To compare the efficacy of the RIC and TCD approaches, we evaluated the outcomes of patients age >50 years with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) who underwent allo-HCT from an HLA-matched donor with one of these strategies. Baseline characteristics were comparable in the patients receiving TCD (n = 204) and those receiving RIC (n = 151), except for a higher proportion of unrelated donors (68% versus 40%; P  < .001) and a higher comorbidity burden (Hematopoietic Cell Transplantation Comorbidity Index [HCT-CI] ≥3: 51% versus 38%; P  < .001) in the TCD cohort. Analysis of outcomes at 3 years showed a higher chronic graft-versus-host disease (GVHD)/relapse-free survival (CRFS) (51% versus 7%; P  < .001), lower incidences of grade II-IV acute GVHD (18% versus 46% at day +180) and chronic GVHD (6% versus 55% at 3 years; P  < .001), and a lower incidence of relapse (19% versus 33% at 3 years; P  = .001) in the TCD group compared with the RIC group. Relapse-free survival (RFS), overall survival (OS), and NRM were similar in the 2 groups. Combining transplantation approach (RIC versus TCD) and comorbidity burden (HCT-CI 0-2 versus ≥3), patients with an HCT-CI score of 0-2 seemed to benefit from the TCD approach. In conclusion, in this retrospective study, the use of a CD34 + cell-selected graft and a myeloablative conditioning regimen was associated with higher CRFS and similar RFS and OS compared with unmodified allo-RIC in patients age >50 years with AML and MDS. [ABSTRACT FROM AUTHOR]

This paper describes the sensitivity of both the orbital frame domain selection and the gravity model on the performance of on-board real-time orbit determination. Practical error sources, which affect the navigation solution of spaceborne global positioning system (GPS) receivers, are analyzed first. Then, a reasonable orbital frame (radial, in-track, cross-track (RIC)) is proposed to clearly represent the characteristics of the error in order to improve the performance of the orbit determination (OD) logic. In addition, the sensitivity of the gravity model affecting the orbit determination logic is analyzed by comparison with the precise orbit ephemeris (POE) of the Challenging Minisatellite Payload (CHAMP) satellite, and it is confirmed that the Gravity Recovery And Climate Experiment (GRACE) Gravity Model 03 (GGM03) outperforms the Earth Gravity Model 1996 (EGM96). The effects of both proposed orbit frames and the gravity model on the orbit determination logic are verified using a GPS simulator and observation data from the CHAMP satellite. Moreover, the practical performance of on-board real-time orbit determination logic is verified by updating the software of the spaceborne GPS receiver, GPS-12, on DubaiSat-2 operating at low Earth orbit (LEO). The results show that the position accuracy of on-board real-time orbit determination logic in GPS-12 is improved by 59%, from 12.6 m (1 σ) to 5.1 m (1 σ), after applying the proposed methods. The velocity accuracy is also improved by 57%, from 13.7 mm/s (1 σ) to 5.9 mm/s (1 σ).

The aim of this paper is to define the main subcomponents of radical innovation culture (RIC) and investigate their impact on non-financial business performance in the Croatian manufacturing industry. The influence of autonomy, cannibalisation, proactiveness and risk-taking on firm effectiveness, customer satisfaction and time-to-market was examined by PLS-SEM of quantitative data from a survey of 203 Croatian manufacturing firms. Results suggest that RIC subcomponents may be divided into two groups, according to their influence on business performance. The first group, consisting of autonomy and proactiveness, positively influenced business performance. However, the second group, consisting of risk-taking and cannibalisation, had no influence on business performance. Implications of the research contribute to understanding of radical innovation culture in transitional economies. [ABSTRACT FROM AUTHOR]

In February 2015 Cofra Dynamic Compaction (CDC), a heavy Rapid Impact Compaction (RIC) technique to compact granular subsoil, was performed on the Berth 9 Quay Extension project in Felixstowe, UK. The extension consists of a 15.000m2 reclamation between sheet pile walls. The compaction of the reclamation was required to reduce future settlements and improve the properties of the sand behind the quay wall. An extensive compaction trial was performed before the start of the project to assess the compaction procedures and work method in relation to the specifications but also to assess the impact of the compaction on the Quay wall. Compaction effort was monitored during compaction with the use of the crane monitoring system which registers the (induced) settlement with increasing blows. The effect of the compaction has been measured with the use of pre- and post-compaction CPT's. The main quay wall displacements were continuously monitored by a manual station and a robotic total station. During the trial an inclinometer was used to gather more data. The paper focusses on the gathered data, findings and observations during the project and the compaction trials. [ABSTRACT FROM AUTHOR]

Repair of Iron Centres (RICs) are a widely-spread family of diiron proteins involved in the protection of iron–sulphur-containing enzymes from nitrosative and oxidative stress. Here, homology-based modelling was used to predict putative ligands of the RIC diiron centre in E. coli . Site-directed mutagenesis studies showed that several conserved residues modulate the spectroscopic properties of the diiron centre, and mutations in H129, E133 and E208 abrogated RIC ability to protect aconitase. Taken together, these data led to a structural model of a diiron centre inserted in a four-helix bundle fold and coordinated by H84, H129, H160, H204, E133 and E208. Moreover, two μ-carboxylate bridges involving E133 and E208 were found to be required for assembly of a stable diiron centre. [ABSTRACT FROM AUTHOR]