Error-free Process Research Articles

Perancangan Sistem Informasi Penerimaan Siswa Baru di SMK Harapan Bangsa Berbasis Web Menggunakan CodeIgniter 4

The admission of new students is a critical process in educational institutions, designed to select candidates based on specific criteria set by the school. This process typically involves multiple stages, including registration, selection through testing, and the announcement of results. However, at SMK Harapan Bangsa, this process has been managed manually using paper-based documentation and Microsoft Excel, which is inefficient and prone to errors. This study aims to develop a web-based information system for new student admissions using the CodeIgniter 4 framework and MySQL database to streamline and enhance the process. The software development methodology employed in this research is the Waterfall model, which consists of analysis, design, implementation, and system testing stages. The result of this research is an information system that simplifies the access to new student admission information for parents and students, enabling them to register online and monitor the selection results more efficiently. Additionally, the system supports the school in automatically archiving and organizing registration data. This web-based solution offers a more structured and error-free process, significantly improving the overall efficiency and accuracy of the admissions procedure.

Transcutaneous cervical vagus nerve stimulation improves sensory performance in humans: a randomized controlled crossover pilot study

Accurate senses depend on high-fidelity encoding by sensory receptors and error-free processing in the brain. Progress has been made towards restoring damaged sensory receptors. However, methods for on-demand treatment of impaired central sensory processing are scarce. Prior invasive studies demonstrated that continuous vagus nerve stimulation (VNS) in rodents can activate the locus coeruleus-norepinephrine system to rapidly improve central sensory processing. Here, we investigated whether transcutaneous VNS improves sensory performance in humans. We conducted three sham-controlled experiments, each with 12 neurotypical adults, that measured the effects of transcutaneous VNS on metrics of auditory and visual performance, and heart rate variability (HRV). Continuous stimulation was delivered to cervical (tcVNS) or auricular (taVNS) branches of the vagus nerve while participants performed psychophysics tasks or passively viewed a display. Relative to sham stimulation, tcVNS improved auditory performance by 37% (p = 0.00052) and visual performance by 23% (p = 0.038). Participants with lower performance during sham conditions experienced larger tcVNS-evoked improvements (p = 0.0040). Lastly, tcVNS increased HRV during passive viewing, corroborating vagal engagement. No evidence for an effect of taVNS was observed. These findings validate the effectiveness of tcVNS in humans and position it as a method for on-demand interventions of impairments associated with central sensory processing dysfunction.

Abstract B013: A quest for deeper understanding of BRCA2 Variants of Uncertain Significance (VUS)

Abstract Deleterious mutations in homology-directed repair pathway genes impact both future cancer risk and therapeutic intervention options for cancer diagnosis and prognosis. Homology-directed repair pathway is a high-fidelity DNA repair pathway for resolving double-strand breaks (DSBs) throughout the human genome. BRCA2, as a homology-directed repair factor, is essential to ensure genome integrity through an error-free process. Deleterious BRCA2 mutations increase the lifetime risk of breast, ovarian, melanoma, prostate, and pancreatic cancers. Deleterious BRCA2 mutations cover only 25% of the total BRCA2 mutations identified in the population by genetic testing whereas 60% are mutations with unknown connection to the disease called Variants of Uncertain Significance (VUS). The majority of BRCA2 VUS are missense mutations with one point mutation which could potentially alter BRCA2 cellular localization and/or nuclear functions. Thus, evaluating BRCA2 cellular localization and function in BRCA2 missense carriers and tumors is urgently needed to provide clinical guidance regarding cancer risk and treatment options. We have identified a paradoxical relationship between BRCA2 nuclear import and treatment. Deleterious missense mutations in the DNA binding domain of BRCA2 direct the protein to the cytosol which increase sensitivity to PARP inhibitors (PARPi) and platinum drugs. Therefore, although BRCA2 mislocalization might be a cause of cancer, keeping it out of the nucleus allows for much better treatment outcomes. Here, we present how BRCA2 cancer-driver missense mutations lead to cytosolic mislocalization and how BRCA2 localization can be used as a diagnostic tool to stratify patients. Our robust multi-step molecular approach will guide future clinical decision rules surrounding BRCA2 VUS. By providing reliable and accurate functional assays to correctly evaluate the pathogenicity of BRCA2 VUS, our goal is to improve personalized medicine by providing actionable information to patients and their physicians. Citation Format: Cole Niedmann, Judit Jimenez Sainz. A quest for deeper understanding of BRCA2 Variants of Uncertain Significance (VUS) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr B013.

An Overview of Different Fruit Crop Models in the last 40 Years to Date with Their Main Uses

Horticulture is a versatile field which encompasses a plethora of day to day strategic decisions like varietal selection, optimisation of resources, understanding the mechanisms of the phenology, identification of plant invaders both in the micro and macro level, wise and judicious use of plant protectants, yield prediction & assessment, post harvesting & handling, strategic way of understanding the pulse of consumer’s popular demands and efficient way of marketing. Fruit trees are perennial unlike annual vegetable and cereal crops where there is a high prerequisite for efficient modelling of canopy architecture, photosynthesis, nutrient uptake, pest forecasting etc where the ill-effects of climate change are bringing out huge losses in the existing germplasm, annual turnover of the farmers and emergence of unheard pests and diseases. An invincible foresight or preparedness against such vagaries can be brought out by efficient modelling mechanisms combining the physiology, phenology and vital requirements of fruit trees with the interacting ecosystem of the land where it is present. Extrapolating such models from the local level to a general situations always gives fruitful results and it further aids in strengthening the present protocols. With the advancement of machine learning and deep learning in precision agriculture, problems of farmers and orchardists are being solved at a faster pace with the help of sensors in identification of problems and its alleviation using fast and error-free processing at pre-harvesting, harvesting and post-harvesting stages of fruit crops. In fact it is also one of the major concerns among people regarding the complete replacement of human power in the crucial decision support systems for agriculture and farming.

The Introduction of Robotics to an Outpatient Dispensing and Medication Management Process in Saudi Arabia: Retrospective Review of a Pharmacy-led Multidisciplinary Six Sigma Performance Improvement Project.

BackgroundOutpatient pharmacy management aims for improved patient safety, improved quality of service, and cost reduction. The Six Sigma method improves quality by eliminating variability, with the goal of a nearly error-free process. Automation of pharmacy tasks potentially offers greater efficiency and safety.ObjectiveThe goal was to measure the impact that integration of automation made to service, safety and efficiency, staff reallocation and reorientation, and workflow in the outpatient pharmacy department. The Six Sigma problem definition to be resolved was as follows: The current system of outpatient dispensing denies quality to patients in terms of waiting time and contact time with pharmacy professionals, incorporates risks to the patient in terms of mislabeling of medications and the incomplete dispensing of prescriptions, and is potentially wasteful in terms of time and resources.MethodsWe described the process of introducing automation to a large outpatient pharmacy department in a university hospital. The Six Sigma approach was used as it focuses on continuous improvement and also produces a road map that integrates tracking and monitoring into its process. A review of activity in the outpatient department focused on non-value-added (NVA) pharmacist tasks, improving the patient experience and patient safety. Metrics to measure the impact of change were established, and a process map analysis with turnaround times (TATs) for each stage of service was created. Discrete events were selected for correction, improvement, or mitigation. From the review, the team selected key outcome metrics, including storage, picking and delivery dispensing rates, patient and prescription load per day, average packs and lines per prescription, and lines held. Our goal was total automation of stock management. We deployed 2 robotic dispensing units to feed 9 dispensing desks. The automated units were integrated with hospital information technology (HIT) that supports appointments, medication records, and prescriptions.ResultsPostautomation, the total patient time in the department, including the time interacting with the pharmacist for medication education and counseling, dropped from 17.093 to 11.812 digital minutes, with an appreciable increase in patient-pharmacist time. The percentage of incomplete prescriptions dispensed versus orders decreased from 3.0% to 1.83%. The dispensing error rate dropped from 1.00% to 0.24%. Assessed via a “basket” of medications, wastage cost was reduced by 83.9%. During implementation, it was found that NVA tasks that were replaced by automated processes were responsible for an extensive loss of pharmacist time. The productivity ratio postautomation was 1.26.ConclusionsThe Six Sigma methodology allowed for rapid transformation of the medication management process. The risk priority numbers (RPNs) for the “wrong patient-wrong medication error” reduced by a ratio of 5.25:1 and for “patient leaves unit with inadequate counseling” postautomation by 2.5:1. Automation allowed for ring-fencing of patient-pharmacist time. This time needs to be structured for optimal effectiveness.

Data-Driven Fault Detection in Industrial Batch Processes Based on a Stochastic Hybrid Process Model

This paper presents a novel fault detection approach for industrial batch processes. The batch processes under consideration are characterized by the interaction between discrete system modes and non-stationary continuous dynamics. Therefore, a stochastic hybrid process model (SHPM) is introduced, where process variables are modeled as time-variant Gaussian distributions, which depend on hidden system modes. Transitions between the system modes are assumed to be either autonomous or to be triggered by observable events such as on/off signals. The model parameters are determined from training data using expectation-maximization techniques. A new fault detection algorithm is proposed, which assesses the likelihoods of sensor signals on the basis of the stochastic hybrid process model. Evaluation of the proposed fault detection system has been conducted for a penicillin production process, with the results showing a significant improvement over the existing baseline methods.Note to Practitioners—Automatic fault detection makes it possible to limit the effects of faults by taking countermeasures at an early stage. In this work, a data-driven fault detection method for industrial batch processes is proposed, in which the underlying process model is learned from training data. The proposed fault detection system can be used for various industrial batch processes without the need for complex and error-prone manual configuration. In contrast to many other data-driven approaches such as neural networks, only a few process cycles are required to create a robust process model. It should be noted that in data-driven fault detection methods, the training data should cover a large part of the process states that occur during error-free process cycles. The developed method is therefore particularly suitable for cyclical processes, which, however, can have alternative process paths and variability between the process cycles.

Impact of Industry 4.0 on Human Resource Process

This paper is aimed at understanding the impact of industry 4.0 on the Human Resources Management Process by use of specific technologies. Industry 4.0 made HR Processes easy, accurate, and fast. The study focuses mainly on, the efficiency of AI and HR automation based on time consumption and error-free process and how far it is efficient in engaging employees with Data Analytics. In this research, the impact of Industry 4.0 on HR is assessed by getting responses from HR Managers and HR Staff in the organisation. Descriptive research design is used in this project and the Judgmental sampling method is used for samples. Here the impact of these technologies is assessed with respective employee engagement, process automation, and cost-effectiveness.

Six Sigma in blood transfusion services: A dream too big in a third world country?

Transfusion errors can occur anywhere from blood donation to final blood transfusion. They are a source of increased cost and patient mortality. Automated workflows can reduce transcription errors, but resource-poor centres still use semi-automated/manual method for testing including manual labelling of column agglutination cards/testing tubes. Missing out any details on these cards can lead to errors in reporting results, wastage and loss of resources and effort. The aim of this study was to implement Six Sigma DMAIC (Define, Measure, Analyse, Improve and Control) methodology to reduce transcription errors while labelling gel card in immunohaematology lab to zero defect. In this prospective study, transcription errors while manually performing 200 tests with 1400 opportunities were analysed. Baseline variables like number of errors, defects per million opportunities and sigma level in our current setup were measured. With the application of DMAIC methodology, root cause analysis for each error using Ishikawa diagram and structured Interviews were done to identify causes. A multipronged approach to deal with errors was done to improve critical areas using brainstorming sessions and developing training sheets for practice. After implementing the changes, baseline variables were reanalysed. Application of DMAIC resulted in an overall reduction in defects from 34.86% to 0.56% with sigma level improvement from 1.89 to 4.08. Six Sigma methodology can be used in a resource-poor setting even with lack of automation to ensure error-free process flow.

Tyrosyl-DNA phosphodiesterases are involved in mutagenic events at a ribonucleotide embedded into DNA in human cells.

Ribonucleoside triphosphates are often incorporated into genomic DNA during DNA replication. The accumulation of unrepaired ribonucleotides is associated with genomic instability, which is mediated by DNA topoisomerase 1 (Top1) processing of embedded ribonucleotides. The cleavage initiated by Top1 at the site of a ribonucleotide leads to the formation of a Top1-DNA cleavage complex (Top1cc), occasionally resulting in a DNA double-strand break (DSB). In humans, tyrosyl-DNA phosphodiesterases (TDPs) are essential repair enzymes that resolve the trapped Top1cc followed by downstream repair factors. However, there is limited cellular evidence of the involvement of TDPs in the processing of incorporated ribonucleotides in mammals. We assessed the role of TDPs in mutagenesis induced by a single ribonucleotide embedded into DNA. A supF shuttle vector site-specifically containing a single riboguanosine (rG) was introduced into the human lymphoblastoid TK6 cell line and its TDP1-, TDP2-, and TDP1/TDP2-deficient derivatives. TDP1 and TDP2 insufficiency remarkably decreased the mutant frequency caused by an embedded rG. The ratio of large deletion mutations induced by rG was also substantially lower in TDP1/TDP2-deficient cells than wild-type cells. Furthermore, the disruption of TDPs reduced the length of rG-mediated large deletion mutations. The recovery ratio of the propagated plasmid was also increased in TDP1/TDP2-deficient cells after the transfection of the shuttle vector containing rG. The results suggest that TDPs-mediated ribonucleotide processing cascade leads to unfavorable consequences, whereas in the absence of these repair factors, a more error-free processing pathway might function to suppress the ribonucleotide-induced mutagenesis. Furthermore, base substitution mutations at sites outside the position of rG were detected in the supF gene via a TDPs-independent mechanism. Overall, we provide new insights into the mechanism of mutagenesis induced by an embedded ribonucleotide in mammalian cells, which may lead to the fatal phenotype in the ribonucleotide excision repair deficiency.

Nurse’s knowledge and Practice regarding Medication Errors in Critical Care Units: Descriptive study

Medication administration should be an error-free process as possible. Critical care nurse need to be diligent in discouraging interruptions to prevent harm to the patients who are being cared for. Medication administration errors are a constant occurrence on the unit, and patient safety must be a focus. Aim: to assess nurse’s knowledge and practice regarding medication errors in critical care units. Design: Descriptive exploratory design was utilized to conduct the current study. Settings: The study was conducted in the following critical care units affiliated to Al minia University Hospital ; Intensive care, neurosurgical care, cardiac care, chest care and finally stroke unit. Sampling: A convenient sample consisted of 60 nurses was obtained from previously mentioned settings regardless of their personal characteristics. Tools: Two tools were used; First; A structural interviewing questionnaire to collect demographic data of the studied nurses and their knowledge regarding medication administration errors. Second; medication administration checklist to assess nurses' practice concerning medication administration errors. Results: The study findings showed that nurse’s mean knowledge (Mean+SD =10.7+2.29) and practice (Mean+SD = 23.1+4.58) scores were unsatisfactory regarding medication administration errors. Moreover, no significant differences were found among them by them regarding demographic characteristics' Conclusion: the mean nurse's knowledge and practice were low. Recommendations: The study recommended implementation of comprehensive, interactive, and continuous educational programs regarding drug administration errors

The Suppression of Taboo Word Spoonerisms Is Associated With Altered Medial Frontal Negativity: An ERP Study

The constant internal monitoring of speech is a crucial feature to ensure the fairly error-free process of speech production. It has been argued that internal speech monitoring takes place through detection of conflict between different response options or “speech plans.” Speech errors are thought to occur because two (or more) competing speech plans become activated, and the speaker is unable to inhibit the erroneous plan(s) prior to vocalization. A prime example for a speech plan that has to be suppressed is the involuntary utterance of a taboo word. The present study seeks to examine the suppression of involuntary taboo word utterances. We used the “Spoonerisms of Laboratory Induced Predisposition” (SLIP) paradigm to elicit two competing speech plans, one being correct and one embodying either a taboo word or a non-taboo word spoonerism. Behavioral data showed that inadequate speech plans generally were effectively suppressed, although more effectively in the taboo word spoonerism condition. Event-related potential (ERP) analysis revealed a broad medial frontal negativity (MFN) after the target word pair presentation, interpreted as reflecting conflict detection and resolution to suppress the inadequate speech plan. The MFN was found to be more pronounced in the taboo word spoonerism compared to the neutral word spoonerism condition, indicative of a higher level of conflict when subjects suppressed the involuntary utterance of taboo words.

Chromosome breaks generated by low doses of ionizing radiation in G2-phase are processed exclusively by gene conversion

Four repair pathways process DNA double-strand breaks (DSBs). Among these pathways the homologous recombination repair (HRR) subpathway of gene conversion (GC) affords error-free processing, but functions only in S- and G2-phases of the cell cycle. Classical non-homologous end-joining (c-NHEJ) operates throughout the cell cycle, but causes small deletions and translocations. Similar deficiencies in exaggerated form, combined with reduced efficiency, are associated with alternative end-joining (alt-EJ). Finally, single-strand annealing (SSA) causes large deletions and possibly translocations. Thus, processing of a DSB by any pathway, except GC, poses significant risks to the genome, making the mechanisms navigating pathway-engagement critical to genome stability. Logically, the cell ought to attempt engagement of the pathway ensuring preservation of the genome, while accommodating necessities generated by the types of DSBs induced. Thereby, inception of DNA end-resection will be key determinant for GC, SSA and alt-EJ engagement. We reported that during G2-phase, where all pathways are active, GC engages in the processing of almost 50 % of DSBs, at low DSB-loads in the genome, and that this contribution rapidly drops to nearly zero with increasing DSB-loads. At the transition between these two extremes, SSA and alt-EJ compensate, but at extremely high DSB-loads resection-dependent pathways are suppressed and c-NHEJ remains mainly active. We inquired whether in this processing framework all DSBs have similar fates. Here, we analyze in G2-phase the processing of a subset of DSBs defined by their ability to break chromosomes. Our results reveal an absolute requirement for GC in the processing of chromatid breaks at doses in the range of 1 Gy. Defects in c-NHEJ delay significantly the inception of processing by GC, but leave processing kinetics unchanged. These results delineate the essential role of GC in chromatid break repair before mitosis and classify DSBs that underpin this breakage as the exclusive substrate of GC.

Applications in Security and Evasions in Machine Learning: A Survey

In recent years, machine learning (ML) has become an important part to yield security and privacy in various applications. ML is used to address serious issues such as real-time attack detection, data leakage vulnerability assessments and many more. ML extensively supports the demanding requirements of the current scenario of security and privacy across a range of areas such as real-time decision-making, big data processing, reduced cycle time for learning, cost-efficiency and error-free processing. Therefore, in this paper, we review the state of the art approaches where ML is applicable more effectively to fulfill current real-world requirements in security. We examine different security applications’ perspectives where ML models play an essential role and compare, with different possible dimensions, their accuracy results. By analyzing ML algorithms in security application it provides a blueprint for an interdisciplinary research area. Even with the use of current sophisticated technology and tools, attackers can evade the ML models by committing adversarial attacks. Therefore, requirements rise to assess the vulnerability in the ML models to cope up with the adversarial attacks at the time of development. Accordingly, as a supplement to this point, we also analyze the different types of adversarial attacks on the ML models. To give proper visualization of security properties, we have represented the threat model and defense strategies against adversarial attack methods. Moreover, we illustrate the adversarial attacks based on the attackers’ knowledge about the model and addressed the point of the model at which possible attacks may be committed. Finally, we also investigate different types of properties of the adversarial attacks.

Poly(ADP-Ribose) Polymerase Inhibitors in Pancreatic Cancer: A New Treatment Paradigms and Future Implications.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy. Most of the patients of PDAC present at later stages of disease and have a five-year survival rate of less than 10%. About 5–10% PDAC cases are hereditary in nature and have DNA damage repair (DDR) mutations such as BRCA 1 and 2. Besides having implications on screening and prevention strategies, these mutations can confer sensitivity to platinum-based therapies and determine eligibility for poly(ADP-ribose) polymerase inhibitors (PARPi). In the presence of DDR mutations and PARPi, the cells are unable to utilize the error-free process of homologous recombination repair, leading to accumulation of double stranded DNA breaks and cell death eventually. Various PARPi are in clinical development in PDAC in different subgroup of patients as monotherapies and in combination with other therapeutics. This review would focus on the mechanism of action of PARPi, history of development in PDAC, resistance mechanisms and future directions.

Multiple modal and wavelength conversion process of a 10-Gbit/s signal in a 6-LP-mode fiber.

We demonstrate experimentally a simultaneous threefold modal and wavelength conversion process of a 10-Gbit/s On/Off keying signal in a 1.8-km long graded-index 6-LP-mode fiber. The principle of operation is based on a phase-matched inter-modal four-wave mixing phenomenon occurring between the fundamental mode and 3 higher-order modes of the fiber. The converted signals show well-opened eye-diagrams and error-free processing.

A Technological Innovation to Reduce Prescribing Errors Based on Implementation Intentions: The Acceptability and Feasibility of MyPrescribe.

BackgroundAlthough prescribing of medication in hospitals is rarely an error-free process, prescribers receive little feedback on their mistakes and ways to change future practices. Audit and feedback interventions may be an effective approach to modifying the clinical practice of health professionals, but these may pose logistical challenges when used in hospitals. Moreover, such interventions are often labor intensive. Consequently, there is a need to develop effective and innovative interventions to overcome these challenges and to improve the delivery of feedback on prescribing. Implementation intentions, which have been shown to be effective in changing behavior, link critical situations with an appropriate response; however, these have rarely been used in the context of improving prescribing practices.ObjectiveSemistructured qualitative interviews were conducted to evaluate the acceptability and feasibility of providing feedback on prescribing errors via MyPrescribe, a mobile-compatible website informed by implementation intentions.MethodsData relating to 200 prescribing errors made by 52 junior doctors were collected by 11 hospital pharmacists. These errors were populated into MyPrescribe, where prescribers were able to construct their own personalized action plans. Qualitative interviews with a subsample of 15 junior doctors were used to explore issues regarding feasibility and acceptability of MyPrescribe and their experiences of using implementation intentions to construct prescribing action plans. Framework analysis was used to identify prominent themes, with findings mapped to the behavioral components of the COM-B model (capability, opportunity, motivation, and behavior) to inform the development of future interventions.ResultsMyPrescribe was perceived to be effective in providing opportunities for critical reflection on prescribing errors and to complement existing training (such as junior doctors’ e-portfolio). The participants were able to provide examples of how they would use “If-Then” plans for patient management. Technology, as opposed to other methods of learning (eg, traditional “paper based” learning), was seen as a positive advancement for continued learning.ConclusionsMyPrescribe was perceived as an acceptable and feasible learning tool for changing prescribing practices, with participants suggesting that it would make an important addition to medical prescribers’ training in reflective practice. MyPrescribe is a novel theory-based technological innovation that provides the platform for doctors to create personalized implementation intentions. Applying the COM-B model allows for a more detailed understanding of the perceived mechanisms behind prescribing practices and the ways in which interventions aimed at changing professional practice can be implemented.

An integrated single vendor–buyer inventory model for imperfect production process with stochastic demand in controllable lead time

An integrated single vendor, single buyer inventory policy is incorporated in a continuous review model with stochastic demand. The production process is assumed to involve deterioration process and produces a certain number of defective items. In the real life production environment, it can often be observed that defective items are produced due to imperfect production processes. A situation in which the vendor invests money to improve the quality of the production process and thereby reduce the defective percentage is considered. 100% error-free screening process adopted by the buyer to separate the defective and non defective items is incorporated to focus on the varying inventory holding costs. Shortages are allowed and completely backlogged. In realistic circumstance, when an order is placed, the products will be delivered only after a certain period of time (lead time). But, owing to tough competition, the buyer may pay an extra amount in order to reduce the lead time. This realistic assumption is incorporated in this model. The model is formulated by allowing the lead time demand to be distributions free and follow a normal distribution. The prime motive is to determine the optimal policies regarding optimal order quantity, reorder point, lead time and the number of lots delivered in a production run by minimizing the expected total cost of the system considered.

Structural basis for the molecular interactions in DNA damage tolerances.

DNA damage tolerance (DDT) is a cell function to avoid replication arrest by DNA damage during DNA replication. DDT includes two pathways, translesion DNA synthesis (TLS) and template-switched DNA synthesis (TS). DDT is regulated by ubiquitination of proliferating cell nuclear antigen that binds to double-stranded DNA and functions as scaffold protein for DNA metabolism. TLS is transient DNA synthesis using damaged DNA as a template by error-prone DNA polymerases termed TLS polymerases specialized for DNA damage. TS, in which one newly synthesized strand is utilized as an undamaged template for replication by replicative polymerases, is error-free process. Thus, DDT is not inherently a repair pathway. DDT is a mechanism to tolerate DNA damage, giving priority to DNA synthesis and enabling finish of DNA replication for cell survival and genome stability. DDT is associated with cancer development and thus is of great interest in drug discovery for cancer therapy. This review article describes recent progress in structural studies on protein-protein and protein-DNA complexes involved in TLS and TS, providing the molecular mechanisms of interactions in DDT.

Design of individual re-contouring processes

The re-contouring process of turbine blades is performed subsequently to the material deposit and restores the shape of the blade. Each process within the process chain has to be adapted to an individual repair case depending on size, location and specification of the damage. Each damaged blade represents a batch size of one. Hence, there is no run-in on the machine tool. This leads to the requirement of an error-free process from the very beginning. Therefore, a reliable process design is needed, including an evaluation of technological blade properties. This paper introduces an integrated method for the design of re-contouring processes. The presented conceptual design considers special requirements regarding an individual repair case, e.g. an individual blade shape, blade properties and material deposit. The method encompasses the definition of an individual repair case and the tool path planning using an interface of a commercial software for computer aided manufacturing (CAM). For evaluation of the tool path, the method contains a high-resolution material removal simulation and a downstream analysis of engagement conditions.

Combining electron microscopy with single molecule DNA fiber approaches to study DNA replication dynamics

Replication stress is a crucial driver of genomic instability. Understanding the mechanisms of replication stress response is instrumental to improve diagnosis and treatment of human disease. Electron microscopy (EM) is currently the technique of choice to directly visualize a high number of replication intermediates and to monitor their remodeling upon stress. At the same time, DNA fiber analysis is useful to gain mechanistic insight on how genotoxic agents perturb replication fork dynamics genome-wide at single-molecule resolution. Combining these techniques has proven invaluable to achieve a comprehensive view of the mechanisms that ensure error-free processing of damaged replication forks. Here, we review how EM and single-molecule DNA fiber approaches can be used together to shed light into the mechanisms of replication stress response and discuss important cautions to be taken into account when comparing results obtained by EM and DNA fiber.