PNU-74654 Suppresses TNFR1/IKB Alpha/p65 Signaling and Induces Cell Death in Testicular Cancer

Testicular cancer (TC) is a rare malignancy worldwide and is the most common malignancy in males aged 15–44 years. The Wnt/β-catenin signaling pathway mediates numerous essential cellular functions and has potentially important effects on tumorigenesis and cancer progression. The search for drugs to inhibit this pathway has identified a small molecule, PNU-74654, as an inhibitor of the β-catenin/TCF4 interaction. We evaluated the therapeutic role of PNU-74654 in two TC cell lines, NCCIT and NTERA2, by measuring cell viability, cell cycle transition and cell death. Potential pathways were evaluated by protein arrays and Western blots. PNU-74654 decreased cell viability and induced apoptosis of TC cells, with significant increases in the sub G1, Hoechst-stained, Annexin V-PI-positive rates. PNU-74654 treatment of both TC cell lines inhibited the TNFR1/IKB alpha/p65 pathway and the execution phase of apoptosis. Our findings demonstrate that PNU-74654 can induce apoptosis in TC cells through mechanisms involving the execution phase of apoptosis and inhibition of TNFR1/IKB alpha/p65 signaling. Therefore, small molecules such as PNU-74654 may identify potential new treatment strategies for TC.

Local Post-hoc Explainable Methods for Adversarial Text Attacks

Deep learning models have significantly advanced various natural language processing tasks. However, they are strikingly vulnerable to adversarial text attacks, even in the black-box setting where no model knowledge is accessible to hackers. Such attacks are conducted with a two-phase framework: 1) a sensitivity estimation phase to evaluate each element’s sensitivity to the target model’s prediction, and 2) a perturbation execution phase to craft the adversarial examples based on estimated element sensitivity. This study explored the connections between the local post-hoc explainable methods for deep learning and black-box adversarial text attacks and proposed a novel eXplanation-based method for crafting Adversarial Text Attacks (XATA). XATA leverages local post-hoc explainable methods (e.g., LIME or SHAP) to measure input elements’ sensitivity and adopts the word replacement perturbation strategy to craft adversarial examples. We evaluated the attack performance of the proposed XATA on three commonly used text-based datasets: IMDB Movie Review, Yelp Reviews-Polarity, and Amazon Reviews-Polarity. The proposed XATA outperformed existing baselines in various target models, including LSTM, GRU, CNN, and BERT. Moreover, we found that improved local post-hoc explainable methods (e.g., SHAP) lead to more effective adversarial attacks. These findings showed that when researchers constantly advance the explainability of deep learning models with local post-hoc methods, they also provide hackers with weapons to craft more targeted and dangerous adversarial attacks.

Local Post-hoc Explainable Methods for Adversarial Text Attacks

Deep learning models have significantly advanced various natural language processing tasks. However, they are strikingly vulnerable to adversarial text attacks, even in the black-box setting where no model knowledge is accessible to hackers. Such attacks are conducted with a two-phase framework: 1) a sensitivity estimation phase to evaluate each element’s sensitivity to the target model’s prediction, and 2) a perturbation execution phase to craft the adversarial examples based on estimated element sensitivity. This study explored the connections between the local post-hoc explainable methods for deep learning and black-box adversarial text attacks and proposed a novel eXplanation-based method for crafting Adversarial Text Attacks (XATA). XATA leverages local post-hoc explainable methods (e.g., LIME or SHAP) to measure input elements’ sensitivity and adopts the word replacement perturbation strategy to craft adversarial examples. We evaluated the attack performance of the proposed XATA on three commonly used text-based datasets: IMDB Movie Review, Yelp Reviews-Polarity, and Amazon Reviews-Polarity. The proposed XATA outperformed existing baselines in various target models, including LSTM, GRU, CNN, and BERT. Moreover, we found that improved local post-hoc explainable methods (e.g., SHAP) lead to more effective adversarial attacks. These findings showed that when researchers constantly advance the explainability of deep learning models with local post-hoc methods, they also provide hackers with weapons to craft more targeted and dangerous adversarial attacks.

Combining Action Observation Treatment with a Brain–Computer Interface System: Perspectives on Neurorehabilitation

Action observation treatment (AOT) exploits a neurophysiological mechanism, matching an observed action on the neural substrates where that action is motorically represented. This mechanism is also known as mirror mechanism. In a typical AOT session, one can distinguish an observation phase and an execution phase. During the observation phase, the patient observes a daily action and soon after, during the execution phase, he/she is asked to perform the observed action at the best of his/her ability. Indeed, the execution phase may sometimes be difficult for those patients where motor impairment is severe. Although, in the current practice, the physiotherapist does not intervene on the quality of the execution phase, here, we propose a stimulation system based on neurophysiological parameters. This perspective article focuses on the possibility to combine AOT with a brain–computer interface system (BCI) that stimulates upper limb muscles, thus facilitating the execution of actions during a rehabilitation session. Combining a rehabilitation tool that is well-grounded in neurophysiology with a stimulation system, such as the one proposed, may improve the efficacy of AOT in the treatment of severe neurological patients, including stroke patients, Parkinson’s disease patients, and children with cerebral palsy.

Unconventional Drilling and Creative Solutions Delivered World Record a Multi-Laterals Fishbone all Legs Drilled, Accessed and Stimulated First Attempt - Case Study from Kuwait

Despite being the first area for oil to be found in Kuwait in mid 1930's, Bahra's oil production remained largely unexploited until 2015, when a major development campaign targeting one of its tight carbonate reservoirs through horizontal drilling and multi-stage frack completions was commissioned. Nonetheless, with the development and exploration initiatives underway, surface congestion is the primary challenge. As the number of wells increased the need for unconventional well profiles became more demanding. The multi-lateral fishbone approach was designed to have a total of four laterals with approximately 3000 ft each. Lessons learned from previous level-1 multi-laterals drilled in North Kuwait indicated that the primary challenge remained to be the ability to drill a smooth bore hole profile across the junctions to successfully re-access and stimulate all the drilled legs with coil-tubing to maximize production. Kuwaiti Operator Reservoir and study team were looking for an alternate solution to increase the production in Bahra using multi-laterals technics in the same reservoir to stimulate and sustain production in calcite reservoir. Historically only three wells were drilled experimenting challenges and failures to open hole sidetrack leading to have long time to complete the wells with maximum 3 legs as record including the mother hole. RST team asked to drill a well with 4 legs, each leg following the same azimuth with the condition to be 300 ft apart. The thorough planning exercise completed and the close follow-up to the approved design of service during execution phase resulted in the successful delivery of the first four legs fishbone in Kuwait with Zero Non-Productive Time. In addition to achieving all the geological targets, the smooth borehole profile helped ensure successful re-entry and stimulation of all four legs in the same run achieving the well challenge using the unique

How a Single Field Development is Becoming a Hub

The work presented in this paper shows how a single development evolved in a main Production Hub to unlock stranded resources, fast tracking subsequent marginal gas discoveries, by improving the flexibility of the subsea and treatment facilities. The approach was supported by a coherent activity about exploration program in the area, JV partnership and contracting strategy. During the Execution phase of a subsea development, a new discovery was made in deep water, 35 km from the Floating Production Unit (FPU). Following this discovery, given the potential for further developments in the area (stranded gas reservoirs and further new gas discoveries), the decision of considering the FPU as a future Production Hub has been taken and FPU has been converted accordingly. The inlet facilities have been designed to guarantee the possibility of receiving well fluids at different pressure levels (high pressure for the new developments and low pressure for productions in depletion) with high production flexibility. Several verifications have been performed to maximize the production flowrates at different pressure values, according to the envelope of data from exploration activities, via adequate arrangements for future expansion. These verifications considered the FPU as it is and with the implementation of minor and major modifications (including retrofitting offshore of new process modules). Design and timing of new equipment as minor/major brownfield modification have been set-up to cope with the modulate field profiles to keep FPU operating flowrate to its maximum value for longer time. In particular, the choice of new booster gas compressors has been planned, in order to select the best configuration for the most recent Hub development plan and to install them at the right time. Converting a barycentric infrastructure in a Hub ensures a significant reduction of CAPEX for future developments (limited to subsea tie-backs only), allowing to reconsider projects previously evaluated economically unsustainable. Moreover, the Hub shall guarantee a long-term gas production by continuous addition of new discoveries in the area, making it an essential facility for the energy future of the Country.

STEP Change in Preventing Stuck Pipe and Tight Hole Events Using Machine Learning

Wellbore stability problems, such as stuck pipe and tight spots, are one of the most critical risks that impact drilling operations. Over several years, Oil and Gas Operator in Middle East has been facing problems associated with stuck pipe and tight spot events, which have a major impact on drilling efficiency, well cost, and the carbon footprint of drilling operations. On average, the operator loses 200 days a year (Non-Productive Time) on stuck pipe and associated fishing operations. Wellbore stability problems are hard to predict due to the varying conditions of drilling operations: different lithology, drilling parameters, pressures, equipment, shifting crews, and multiple well designs. All these factors make the occurrence of a stuck pipe quite hard to mitigate only through human intervention. For this reason, The operator decided to develop an artificial intelligence tool that leverages the whole breadth and depth of operator data (reports, sensor data, well engineering data, lithology data, etc.) in order to predict and prevent wellbore stability problems. The tool informs well engineers and rig crews about possible risks both during the well planning and well execution phase, suggesting possible mitigation actions to avoid getting stuck. Since the alarms are given ahead of the bit, several hours before the possible occurrence of the event, the well engineers and rig crews have ample time to react to the alarms and prevent its occurrence. So far, the tool has been deployed in a pilot phase on 38 wells giving 44 true alarms with a recall of 94%. Since mid-2021 operator has been rolling out the tool scaling to the whole drilling operations (over 40 rigs).

La justicia restaurativa en la ejecución penitenciaria

La participación de la víctima en la fase de ejecución del proceso penal en nuestro ordenamiento es un hecho novedoso que, más allá de la reparación civil, arranca del Estatuto de la víctima en año 2015, el cual introduce la Justicia Restaurativa en ese momento procesal. Este instrumento puede ser una importante alternativa o complemento a la Justicia tradicional en aras de lograr una mejor satisfacción de los intereses de la victima. Siendo este el objetivo, se viene desarrollando desde el año 2019 una experiencia en el CIS “Máximo Carrera” de Valladolid en la cual se trabaja con liberados condicionales, penados clasificados en tercer grado y condenados a la pena de trabajos en beneficio de la comunidad, con el objetivo de elaborar un protocolo de actuación extensible a otros centros. The participation of the victim in the execution phase of the criminal process in our legal order is a novel fact that, beyond civil reparation, starts from the Statute of the victim in 2015, and introduces Restorative Justice at that procedural moment. This instrument may become an important alternative or complement to traditional Justice in order to achieve a better satisfaction of the interests of the victim. A Program dealing with conditional parole inmates, convicts classified in third degree and sentenced to comunity services has been developed in the CIS “Máximo Carrera” of Valladolid since 2019, with the aim of drawing up an action protocol that may be extended to other prisons.

Healthy Caspian Experience helps Boost Drilling Performance in Turkey's Onshore UGS Project

The company is executing an underground gas storage project at an unprecedented scale. The intent of this paper is to demonstrate the execution methodology and technologies that the company employed to achieve within set deadlines and deliver the work on time and under the given budget. This paper, therefore will focus on outlining all planning, design as well as drilling & completions strategies utilized by the operating company during the execution phase. During Phase 2 of the project, the Drilling Contractor was engaged to deliver a total of 40 wells within a short period of time. These wells were planned to expand the total gas storage capacity at the Tuz Golu facility to ca. 5 bcm of natural gas stored in underground salt caverns. Tuz Golu wells are vertical with three (3) casing string wells. These land wells are big bore and commence from the installation of the 30″ conductor at a depth of 120m using a small 150-ton conductor rig. Pre-installation of conductors significantly helped accelerate the project delivery schedule. Main drilling operations commenced in January 2020. Since the structure wasn't fully explored in spite of 2D seismic work and the first phase operations, a number of wells drilled encountered no salt leading to their abandonment. As a result, the total duration of the project was consequently extended. Re-Engineering and lessons learned during execution helped deliver a successful learning curve in both drilling and completion operations. The strategy of the company to drill a well in stages of top hole, main drilling and the completion using multiple rig operations was successful, bringing an overall well time from 55 at the beginning of the project to 20 days per well. Thorough planning and design of the wells allowed the company to deliver the projects with well integrity, full suitable for gas storage operations. As a result, the project was executed on time and well within the planned budget thus delivering an excellent value to the stakeholders and main client. The Drilling Contractor has been proactive to employ this staged approach from the very beginning of the project. Irrespective of the delays the Drilling Contractor continued operations with the intermittent rig count of 4 to 8 rigs. A large scale operation demanded careful planning and continuous application of lessons learnt from the first phase which were successfully embedded and implemented.

Role of Geologists During Tunnel Construction and Face Mapping to Decide the Required Tunnel Support

The stability of underground structures is an important aspect during design, construction and execution Phase. Depending on the geotechnical conditions and influencing factors, different failure modes during execution mode can be expected, and depending on the potential failure modes, boundary conditions and specific construction measures to ensure stability have to be chosen. The most important is developing a realistic estimate of the expected ground conditions and their potential behaviour/failure modes as a result of the excavation. The variability of the geological conditions including local ground structure, ground parameters, stress and ground water conditions requires that a consistent and specific procedure is used. The other is to design an economic and safe excavation and support method for the determined ground behaviours. The discussion of role of geologists during design stage is beyond the scope of the present study. The main objective of this study is to present the role of geologists during the construction stage. Keywords: Geologist, Stress, Behaviour, RMR, Q Value, RQD, Rock Mass