Repair Sequences Research Articles

Glycosaminoglycan-Based Hydrogel Delivery System Regulates the Wound Microenvironment to Rescue Chronic Wound Healing.

Chronic wounds cannot proceed through the normal, orderly, and timely sequence of repair. The adverse cycle between excess reactive oxide species (ROS) and a persistent inflammatory response is an important mechanism of impaired wound healing. Herein, by combining the intrinsic bioactivities of natural polysaccharides and natural drugs, a glycosaminoglycan-based hydrogel delivery system is proposed to regulate the wound microenvironment. Dynamic supramolecular cross-linking enables the hydrogel to easily encapsulate the drug and fully fill the wound area. As the backbone of the hydrogel, heparin captures inflammatory chemokines at the wound site, while hyaluronic acid mimics the function of ECM. The hydrophobic drug curcumin has been ingeniously encapsulated in the hydrogel through micellization, thereby exerting good ROS scavenging ability and anti-inflammatory activity. Evaluations in diabetic mice showed that this antioxidant and anti-inflammatory hydrogel was effective in reducing the influx of immune cells at the wound site and in down-regulating the inflammatory response. Accelerated wound healing was also observed, as evidenced by faster re-epithelialization and better ECM remodeling. The proposed hydrogel can regulate the microenvironment of wounds from multiple aspects and thereby achieve regression of wound repair, which may provide a new therapeutic strategy for chronic wounds.

Comprehensive characterisation of Lynch syndrome and screening strategies: a cohort study of individuals at risk from Latin American genetic registries

Systematic screening for Lynch syndrome is non-existent in most Latin American countries. Until regional guidelines are developed and implemented, patients with colorectal cancer in Latin America are being followed up according to international recommendations. The aim of this study was to characterise the current Lynch syndrome screening method in the region, and to explore the prevalence of Lynch syndrome in a large cohort of individuals at risk. We collected clinical, molecular, and genetic data from patients with high-risk colorectal cancer from 24 existing genetic registries and centres from nine countries in Latin America (Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, Puerto Rico, and Uruguay). Information on clinical history, personal or family history of cancer, screening strategy, and molecular and genetic testing was collected by the participating registries through standardised reporting tools. The compiled information was curated and imported into a PostgreSQL database at the Institute of Cancer Research (Oslo, Norway). Data from 1684 patients were included. Universal screening was the most commonly reported screening strategy involved in detection of Lynch syndrome (used to detect Lynch syndrome in 1133 [67·3%] of 1684 patients). The most common method included only immunohistochemistry (336 [29·7%] of 1133), followed by a combination of immunohistochemistry plus microsatellite instability assay (168 [14·8%] of 1133), or immunohistochemistry, BRAFV600E testing, microsatellite instability assay, and MLH1 methylation analysis (133 [11·7%] of 1133). The mutation rate detected with germline mismatch repair sequencing when applying the universal screening strategy was 60 (51%) of 117 versus 87 (47%) of 182 with the clinical criteria. The median age of patients with Lynch syndrome was 40 years (IQR 34-49) and the predominant tumour location was the right colon (109 [43%] of 254), for which the most common stage at diagnosis was stage II (92 [36%] of 254). No multiple tumours were detected in 171 (67%) of 252 patients. Amsterdam criteria were met by 159 (63%) of 254 patients and revised Bethesda guidelines were met by 136 (54%) patients. Our results have implications for the design of future Lynch syndrome screening programmes, but further studies are needed to assess the cost-effectiveness and burden on genetic counselling services with expanded universal testing for Lynch syndrome. Norwegian Cancer Society (contract 194751-2017).

Coaxially Fabricated Dual-Drug Loading Electrospinning Fibrous Mat with Programmed Releasing Behavior to Boost Vascularized Bone Regeneration.

In clinical treatment, the bone regeneration of critical-size defects is desiderated to be solved, and the regeneration of large bone segment defects depends on early vascularization. Therefore, overcoming insufficient vascularization in artificial bone grafts may be a promising strategy for critical-size bone regeneration. Herein, a novel dual-drug programmed releasing electrospinning fibrous mat (EFM) with a deferoxamine (DFO)-loaded shell layer and a dexamethasone (DEX)-loaded core layer is fabricated using coaxial electrospinning technology, considering the temporal sequence of vascularization and bone repair. DFO acts as an angiogenesis promoter and DEX is used as an osteogenesis inducer. The results demonstrate that the early and rapid release of DFO promotes angiogenesis in human umbilical vascular endothelial cells and the sustained release of DEX enhances the osteogenic differentiation of rat bone mesenchymal stem cells. DFO and DEX exert synergetic effects on osteogenic differentiation via the Wnt/β-catenin signaling pathway, and the dual-drug programmed releasing EFM acquired perfect vascularized bone regeneration ability in a rat calvarial defect model. Overall, the study suggests a low-cost strategy to enhance vascularized bone regeneration by adjusting the behavior of angiogenesis and osteogenesis in time dimension.

Other-Initiated Self-Repairs in Student-Student Interaction: The Frequency of Occurrence and Mechanism

The current study is intended to explore the typology of other-initiated self-repair in term of its frequency of occurrence and to investigate the mechanism of self-repair in an academic setting. To obtain the required data, a classroom conversational analysis was conducted in which the researchers observed a group of graduate students (19 active EFL speakers) in a state university in East Java, Indonesia. Based on the qualitative data analysis, the results of the study revealed that all typologies of other-initiated selfrepair were used depending on the aims the interlocutors try to gain since all typologies have diverse aims and ways. Of all typologies, confirming checks were dominantly used by the participants. Regarding the mechanisms, three types of mechanisms were found; full two-cycle repair, background check, and short-cut repair sequence.

Other-Initiated Self-Repairs in Student-Student Interaction: The Frequency of Occurrence and Mechanism

The current study is intended to explore the typology of other-initiated self-repair in term of its frequency of occurrence and to investigate the mechanism of self-repair in an academic setting. To obtain the required data, a classroom conversational analysis was conducted in which the researchers observed a group of graduate students (19 active EFL speakers) in a state university in East Java, Indonesia. Based on the qualitative data analysis, the results of the study revealed that all typologies of other-initiated selfrepair were used depending on the aims the interlocutors try to gain since all typologies have diverse aims and ways. Of all typologies, confirming checks were dominantly used by the participants. Regarding the mechanisms, three types of mechanisms were found; full two-cycle repair, background check, and short-cut repair sequence.

Computational Application on English Translation System Based on Intelligent Image Text Recognition

This work offers an enhanced intelligent picture text recognition algorithm based on the intelligent image text recognition method to increase the impact of English image text translation. Texture blocks of adaptable size are used to successfully increase the accuracy and efficiency of restoration due to the varying texture information present in various photos. Furthermore, the repair sequence is altered as a result of the improved priority calculation algorithm, and the weight of the structural information is enhanced at the same time. In addition, in order to reduce the overall structural complexity and calculation amount of the system, the gated loop unit is also selected as the RNN structure. Finally, this article constructs an English translation system based on intelligent image text recognition according to the requirements of intelligent image text recognition and designs experiments to evaluate the performance of the system constructed in this article. The experimental statistical results show that the English translation system constructed in this article can basically meet the needs of English image text recognition.

A new technique for genome-wide mapping of nucleotide excision repair without immunopurification of damaged DNA

Nucleotide excision repair functions to protect genome integrity, and ongoing studies using excision repair sequencing (XR-seq) have contributed to our understanding of how cells prioritize repair across the genome. In this method, the products of excision repair bearing damaged DNA are captured, sequenced, and then mapped genome-wide at single-nucleotide resolution. However, reagent requirements and complex procedures have limited widespread usage of this technique. In addition to the expense of these reagents, it has been hypothesized that the immunoprecipitation step using antibodies directed against damaged DNA may introduce bias in different sequence contexts. Here, we describe a newly developed adaptation called dA-tailing and adaptor ligation (ATL)–XR-seq, a relatively simple XR-seq method that avoids the use of immunoprecipitation targeting damaged DNA. ATL-XR-seq captures repair products by 3′-dA-tailing and 5′-adapter ligation instead of the original 5′- and 3′-dual adapter ligation. This new approach avoids adapter dimer formation during subsequent PCR, omits inefficient and time-consuming purification steps, and is very sensitive. In addition, poly(dA) tail length heterogeneity can serve as a molecular identifier, allowing more repair hotspots to be mapped. Importantly, a comparison of both repair mapping methods showed that no major bias is introduced by the anti-UV damage antibodies used in the original XR-seq procedure. Finally, we also coupled the described dA-tailing approach with quantitative PCR in a new method to quantify repair products. These new methods provide powerful and user-friendly tools to qualitatively and quantitatively measure excision repair.

Efficacy of concentrated growth factors (CGF) vs normal saline dressing in chronic non healing ulcers

A Chronic non-healing wound is one which has fails to progress through a timely sequence of repair or one that proceeds through the wound healing process without restoring anatomic and functional results. A wide variety of factors is thought to contribute to this problem. Concentrated Growth Factors (CGF) (first developed by Sacco (2006)) is a relatively new technology within the area of regenerative medicine. CGF is an advanced second generation platelet concentrate, obtained with differential continuous centrifugal technology. Use of CGF in management of chronic skin wounds has led to high rates of recovery but further works are required in order to improve the effectiveness of treatment protocols and the comfort and safety of patients. Its application is progressively spreading in the clinical field.

Resilience-Based Repair Strategy for Gas Network System and Water Network System in Urban City

In resilience-based frameworks, optimizing the repair strategy and approaches is important for the recovery of the function of gas network systems (GNS) and water network systems (WNS). According to the resilience quantification results of GNS and WNS for a real example urban city in China, the potential impact of utilizing different repair sequences and repair/replacement approaches was investigated. First, a Monte Carlo simulation-based method was proposed to search for the optimal repair sequence according to the skew of the recovery trajectory (SRT). Under high seismic intensity conditions, the significant difference between the repair sequence corresponding to maximum SRT and minimum SRT indicates that choosing the optimal repair sequence is important in the enhancement of repair efficiency, especially when the pipelines have experienced serious damage. We also discussed the parallel repair strategy, which is more consistent with the practice, and can greatly improve the recovery efficiency compared with the single pipeline repair strategy under large damage conditions; however, under minor damage levels, the parallel repair strategy may result in a certain degree of redundancy. Next, three different repair approaches were thoroughly compared, including the point-by-point repair approach, whole pipeline replacement, and hybrid repair approach. At the condition of high seismic intensity (e.g., macroseismic intensity IX), the resilience curves for the hybrid repair approach and the pipeline replacement approach are overall similar and take less time and economic cost than the point-by-point repair approach. However, when the seismic intensity is low, the point-by-point repair approach is most efficient and has the shortest recovery time. Therefore, the choice of repair approach should be determined by stakeholders based on the specific pipeline’s damage situation. Finally, we calculated the joint resilience curves by allocating different weight factors to GNS and WNS, to represent the proportion of water and gas supply that contributes to community resilience.

CSB-independent, XPC-dependent transcription-coupled repair in Drosophila

Drosophila melanogaster has been extensively used as a model system to study ionizing radiation and chemical-induced mutagenesis, double-strand break repair, and recombination. However, there are only limited studies on nucleotide excision repair in this important model organism. An early study reported that Drosophila lacks the transcription-coupled repair (TCR) form of nucleotide excision repair. This conclusion was seemingly supported by the Drosophila genome sequencing project, which revealed that Drosophila lacks a homolog to CSB, which is known to be required for TCR in mammals and yeasts. However, by using excision repair sequencing (XR-seq) genome-wide repair mapping technology, we recently found that the Drosophila S2 cell line performs TCR comparable to human cells. Here, we have extended this work to Drosophila at all its developmental stages. We find TCR takes place throughout the life cycle of the organism. Moreover, we find that in contrast to humans and other multicellular organisms previously studied, the XPC repair factor is required for both global and transcription-coupled repair in Drosophila.

The Embodied Work of Repairing-for-Teasing in Everyday L2 Talk

This paper focuses on participants’ embodied conduct in the service of action ascription in teasing environments. The teasing activity is sequentially organized as an other-initiated repair sequence in which the other-initiations of repair (OIRs) are used as vehicles for carrying out the teasing actions (see also Schegloff, 1997, 2007; Rossi, 2018). The analysis shows that the double-barreled OIRs are designed as multimodal action packages in which the verbal part is delivered in a serious manner and combined with embodied conduct that typically characterizes repair environments, such as head turns and tilts, forward-leaning, and gestural holds, but produced in exaggerated or pretended manner. The embodied exaggeration and performed character are the key elements contributing to action ascription in teasing environments.

Management of noncerebral malperfusion complicating acute type A dissection.

Vital organ malperfusion in acute type A aortic dissection is associated with worse outcomes, especially when multiple organ systems are involved, and when coronary or mesenteric malperfusion is present. To achieve the two goals of central aortic repair and adequate and timely reperfusion, mechanism and organ-specific strategy in the methods and sequence of repair should be considered. For dynamic aortic malperfusion, reperfusion can be quickly achieved by femoral artery perfusion, and the fenestrated frozen elephant trunk operation, in which the proximal end of device is secured to zone 1 or 2 and distal 1 or 2 supra-aortic vessels are preserved by fenestration of the fabric, seems optimal as a method of central aortic repair. For coronary malperfusion, percutaneous coronary intervention before central aortic repair may have a role. However, it should be kept in mind that the door-to-unloading time is also important to reduce the area of myocardial infarction, and retrograde cardioplegia is not distributed to most of the right ventricle, which can be critical when right coronary malperfusion is present. Static mesenteric malperfusion should be addressed first, and second-look laparotomy should not be hesitated after central aortic repair. The use of a hybrid operating room may be an optimal solution to achieve both goals.

EXAMINING RATER PERCEPTION OF HOLDS AS A VISUAL CUE OF LISTENER NONUNDERSTANDING

AbstractThis study examined whether university students perceive holds (i.e., a listener’s temporary cessation of dynamic movement) as a visual cue of nonunderstanding. Conversations between English second language (L2) university students were sampled to extract episodes of other-initiated repair through open clarification requests (e.g., what?, sorry?). Brief, silent video clips were presented to 60 raters across two experiments who assessed the listener’s comprehension, which was their perception about how well the listener had understood the speaker. Experiment 1 tested whether raters can differentiate between the onset and release of listener holds while Experiment 2 examined whether they are sensitive to the sequential organization of holds. Results indicated that raters clearly differentiated between hold onsets and releases and were sensitive to the temporal position of holds in the entire repair sequence. Taken together, these findings suggest that holds are a reliable signal of nonunderstanding with potential implications for L2 teaching and assessment.

Resilience-driven repair sequencing decision under uncertainty for critical infrastructure systems

Disruptions on critical infrastructure systems (CISs) might affect their normal operation and cause severe social and economic impact. The rapid recovery of post-disaster CISs is crucially important. Based on the authors’ previous work on the deterministic formulation of the repair sequencing decision problem of post-disaster CISs under limited repair resources, this paper considers the uncertainty of the repair time of damaged components and proposes a two-stage stochastic model. To solve the stochastic model, a scenario generation and reduction method is first used to generate a limited number of repair time scenarios, and then an efficient enumeration algorithm is proposed for small-scale disruptions and adopted as a module in a heuristic algorithm for large-scale disruptions. Numerical experiments on three systems are conducted to demonstrate the efficiency of the proposed algorithm. Results show that the proposed algorithm can be applied to the recovery decision of large-scale CISs with extensive disruptions. In addition, results show that for most instances, the stochastic solution solved using a limited number of repair time scenarios might be worse than the solution solved from the deterministic model when judging the two solutions by a huge number of repair time scenarios to sufficiently capture the repair time uncertainty.

A graph convolution network‐deep reinforcement learning model for resilient water distribution network repair decisions

AbstractWater distribution networks (WDNs) are critical infrastructure for communities. The dramatic expansion of the WDNs associated with urbanization makes them more vulnerable to high‐consequence hazards such as earthquakes, which requires strategies to ensure their resilience. The resilience of a WDN is related to its ability to recover its service after disastrous events. Sound decisions on the repair sequence play a crucial role to ensure a resilient WDN recovery. This paper introduces the development of a graph convolutional neural network‐integrated deep reinforcement learning (GCN‐DRL) model to support optimal repair decisions to improve WDN resilience after earthquakes. A WDN resilience evaluation framework is first developed, which integrates the dynamic evolution of WDN performance indicators during the post‐earthquake recovery process. The WDN performance indicator considers the relative importance of the service nodes and the extent of post‐earthquake water needs that are satisfied. In this GCN‐DRL model framework, the GCN encodes the information of the WDN. The topology and performance of service nodes (i.e., the degree of water that needs satisfaction) are inputs to the GCN; the outputs of GCN are the reward values (Q‐values) corresponding to each repair action, which are fed into the DRL process to select the optimal repair sequence from a large action space to achieve highest system resilience. The GCN‐DRL model is demonstrated on a testbed WDN subjected to three earthquake damage scenarios. The performance of the repair decisions by the GCN‐DRL model is compared with those by four conventional decision methods. The results show that the recovery sequence by the GCN‐DRL model achieved the highest system resilience index values and the fastest recovery of system performance. Besides, by using transfer learning based on a pre‐trained model, the GCN‐DRL model achieved high computational efficiency in determining the optimal repair sequences under new damage scenarios. This novel GCN‐DRL model features robustness and universality to support optimal repair decisions to ensure resilient WDN recovery from earthquake damages.

Real-Time Resilience Optimization Combining an AI Agent With Online Hard Optimization

In the highly interdependent environment of a large city, failures in the Electrical Distribution System (EDS) can cause direct or indirect consequences to other critical infrastructures and the well-being of the citizens. To increase the resilience of the supply of electricity to the city, this work combines the pre-training of an AI agent and very fast calculation of the optimum recovery path after the number and location of the electrical faults are known. In the introduced Soft-Hard Optimal Convergence (SHOC) method, machine learning techniques are used to train an AI agent with thousands of off-line scenarios for optimum system restoration. In real-time, after the actual fault information is known, the agent will provide a subset of solutions (soft solution) to be considered for hard optimization algorithms. The Infrastructure Interdependencies Simulator (i2SIM) is used to assist the prioritization of the sequence of fault recovery and topological reconfiguration to minimize the black-out time of the most critical loads. A 70-node distribution system case is used to demonstrate the proposed methodology, with solution times in the order of seconds to find the optimum repair sequence and switches topological reconfiguration to optimize the city's resilience index.

CRISPR-/Cas9-Mediated Precise and Efficient Genome Editing in Drosophila.

The CRISPR/Cas9 system provides the means to make precise and purposeful modifications to the genome via homology-directed repair (HDR). In Drosophila, a wide variety of tools provide flexibility to achieve these ends. Here, we detail a method to generate precise genome edits via HDR that is efficient and broadly applicable to any Drosophila stock or species. sgRNAs are first tested for their cleavage efficiency by injecting embryos with Cas9/sgRNA ribonucleoproteins using commercially available Cas9 protein. Using an empirically validated sgRNA, HDR is performed using a donor repair plasmid that carries two transformation markers. A fluorescent eye marker that can be seamlessly removed using PiggyBac transposase marks integration of the repair sequence. A counter-selection marker that produces small rough eyes via RNAi against eyes absent is used to screen against imprecise HDR events. Altogether, the enhancements implemented in this method expand the ease and scope of achieving precise CRISPR/Cas9 genome edits in Drosophila.

Who Speaks with My Synthesized Voice? Some Roles of Other-initiated Repair in Augmented Intaraction

As conversation analysis shows, all talk is highly collaborative, and meaning is created dialogically and sequentially, via the concerted actions of all the participants involved. In the case of people with communication impairments, the collaborative character of talk is even more manifest. A speaker with dysarthria, for example, may communicate through typing their messages to a text-to-speech communication app or device, using a communication (alphabet) board, or gazing at objects. This article focuses on one type of co-construction effort aimed at helping an augmented speaker to communicate, a process that can be called other-initiated repair. Although this practice is a common way of achieving understanding with people who have communication needs, in some cases repair initiation is used to do more than that. In this paper, I conduct conversation analysis of a video-recording of naturalistic interactions inside a Russian-speaking family involving a 10-year-old girl with dysarthria who communicates with her parents through an eyetracker-controlled computer interface. In this case, her parents use the structural position of repair initiation on the girl’s words not only to clarify the meaning of her message but to continue the preceding polemics over the mom’s birthday present. I argue that although this is just one instance of the use of other-repair in playful communication between family members, The potentiality of providing the type of guessing which aligns with the guesser’s interests is present in other repair sequences. This can be consequential for lives of people with communication needs when done in more official settings. Studying similar repair sequences can help better delineate 'good' scaffolding strategies in co-construction of speech of someone with communication needs.

RECOVERY OF SEWER PIPELINES USING ANCHOR POLYETHYLENE SHEETS

Raising of problem. Microbiological corrosion, which occurs as a result of the vital activity of microorganisms in wastewater, causes the destruction of the vaulted part and significantly reduces the service life of reinforced concrete and concrete drainage pipelines. Partially destroyed pipelines of sewerage networks, operating in various hydrogeological conditions, often at great depths, must be restored using materials that can ensure the reliability of further operation in conditions of microbiological corrosion, cost-effectiveness and ease of repair. These are primarily polymer-based materials. The open method of repair and restoration work on sewer pipelines has significant advantages over trenchless, if their depth is insignificant and urban transport and pedestrian arteries do not interfere with the work. Thus, the development of a technology for repair and restoration of reinforced concrete and concrete collectors destroyed by microbiological corrosion using modern materials based on polymers is an urgent task. Purpose. Development of technology and sequence of repair and restoration work for the restoration of the destroyed vaulted part of sewer reinforced concrete and concrete pipelines by an open method using pneumatic formwork and protective anchor polyethylene sheets. Conclusion. As a result of the research, a technology and sequence of repair and restoration work was developed to restore sewer reinforced concrete and concrete collectors from 5 stages, including the stage of cleaning the collector from corrosion products and destroyed parts, installation of a pneumatic formwork and an anchor polyethylene sheet in the surviving chute part of the collector, installation of metal inventory formwork, restoration by concreting the arch on top of the anchor polyethylene sheet and dismantling of the pneumatic and metal inventory formwork.

Seismic resilient three-stage enhancement for gas distribution network using computational optimization algorithms

A computer-simulation-based three-stage optimization strategy is proposed for the resilience enhancement of urban gas distribution networks (GDNs). In stage I (pre-earthquake stage), the Fixed Proportion and Direct Comparison Genetic Algorithm (FPDC-GA) is applied to select key pipelines need to be strenthened or replaced under limited funding in preparation for future potential earthquakes. In stage II (post-earthquake stage), pressure tests must be carried out according to the gas leakage situation reported by users or detected by devices. The Multi-Label K-Nearest-Neighbor (ML-KNN) algorithm is used to predict the corresponding failed pipelines and optimize the pipeline pressure test order. In stage III (repair stage), a strategy based on a greedy algorithm is applied to optimize the pipeline repair sequence. The proposed methods were applied to the GDN of a city in northern China. The following conclusions were drawn from the results: (1) The FPDC-GA enhanced the robustness and resourcefulness of the GDN system to the maximum level within the available funding budget. (2) The pipeline pressure test order calculated using the ML-KNN algorithm was significantly improved compared with a random pressure test order or one based on the empirical failure probability of pipelines. (3) After optimization using a greedy algorithm, the performance recovery curves under different earthquake conditions were shaped as an exponential function, which indicates that the performance of the GDNs recovered in the most efficient manner. The findings of this study could be useful as tools for the seismic resilience enhancement of GDNs in different stages. The proposed optimization algorithms can also be extended to the lifeline of other networks.