Beyond Chaperoning: UCS Proteins Emerge as Regulators of Myosin-Mediated Cellular Processes.

The UCS (UNC-45/CRO1/She4p) family of proteins has emerged as chaperones specific for the folding, assembly, and function of myosin. UCS proteins participate in various myosin-dependent cellular processes including myofibril organization and muscle functions, cell differentiation, striated muscle development, cytokinesis, and endocytosis. Mutations in the genes that code for UCS proteins cause serious defects in myosin-dependent cellular processes. UCS proteins that contain an N-terminal tetratricopeptide repeat (TPR) domain are called UNC-45. Vertebrates usually possess two variants of UNC-45, the ubiquitous general-cell UNC-45 (UNC-45A) and the striated muscle UNC-45 (UNC-45B), which is exclusively expressed in skeletal and cardiac muscles. Except for the TPR domain in UNC-45, UCS proteins comprise of several irregular armadillo (ARM) repeats that are organized into a central domain, a neck region, and the canonical C-terminal UCS domain that functions as the chaperoning module. With or without TPR, UCS proteins form linear oligomers that serve as scaffolds that mediate myosin folding, organization into myofibrils, repair, and motility. This chapter reviews emerging functions of these proteins with a focus on UNC-45 as a dedicated chaperone for folding, assembly, and function of myosin at protein and potentially gene levels. Recent experimental evidences strongly support UNC-45 as an absolute regulator of myosin, with each domain of the chaperone playing different but complementary roles during the folding, assembly, and function of myosin, as well as recruiting Hsp90 as a co-chaperone to optimize key steps. It is becoming increasingly clear that UNC-45 also regulates the transcription of several genes involved in myosin-dependent cellular processes.

The race for the classification of proximal periprosthetic femoral fractures : Vancouver vs Unified Classification System (UCS) - a systematic review.

BACKGROUND: Periprosthetic femoral fractures (PFFs) represent a major cause for surgical revision after hip arthroplasty with detrimental consequences for patients. The Vancouver classification has been traditionally used since its introduction in 1995. The Unified Classification System (UCS) was described in 2014, to widen the spectrum by aiming for a more comprehensive approach. The UCS also aimed to replace the Vancouver classification by expanding the idea of the Vancouver classification to the whole musculoskeletal apparatus. After introduction of the UCS, the question was raised, whether the UCS found its place in the field of analysing PFFs. Therefore, this systematic review was performed to investigate, the use of the UCS compared to the established Vancouver classification. METHODS: Medline was searched for reports published between 1 January 2016 and 31 November 2020, without language restriction. Included were original articles, irrespective of the level of evidence and case reports reporting on a PFF and using either the Vancouver or the UCS to classify the fractures. Excluded were reviews and systematic reviews. RESULTS: One hundred forty-six studies were included in the analysis. UCS has not been used in a single registry study, giving a pooled cohort size of 3299 patients, compared to 59,178 patients in studies using the Vancouver classification. Since 2016, one study using UCS was published in a top journal, compared to 37 studies using the Vancouver classification (p=0.29). During the study period, the number of yearly publications remained stagnant (p=0.899). CONCLUSIONS: Despite valuable improvement and expansion of the latter UCS, to date, the Vancouver system clearly leads the field of classifying PFFs in the sense of the common use.

Assessment of the reuse of Covid-19 healthy personal protective materials in enhancing geotechnical properties of Najran's soil for road construction: Numerical and experimental study.

The COVID-19 pandemic has not only caused a global health crisis, but it has also had significant environmental and human consequences. During the COVID-19 pandemic, this study focused on emerging challenges in managing healthy personal protective materials (HPPM) in Kingdom of Saudi Arabia, using silty sand (SM) soil as an example since it covers large areas in KSA and in the whole world. The main objective of this paper is to find a novel way to minimize pandemic-related waste by using HPPM as waste materials in road construction. For the first time, a series of experiments was conducted on a mixture of different percentages of shredded HPPM (0, 0.5, 1 and 2%) added to the silty sand (SM) soil for road applications, including soil classification according to the USCS, modified compaction, UCS, UPV, and CBR. In addition, a numerical simulation was performed using geotechnical-based software Plaxis 3D to study the performance of the soil-HPPM mix as a subbase layer in the paving structure under heavy traffic loading. The modified compaction test results show that there is an increase in the optimum moisture content with increasing the HPPM contents from 0.5% to 1% and 2%. However, a reduction in the maximum dry density is observed. The values of dry density and water content at 0%, 0.5%, 1% and 2% pf HPPM are 2.045, 1.98, 1.86 and 1.8 g/cm3 and 7.65% 8%, 8.5% and 9.5%, respectively. The soaked CBR values at 0, 0.5, 1 and 2% HPPM are 23, 30, 8, 2% with the maximum value attained with the addition of 0.5% HPPM. The results of UCS were with the same percentages of HPPM 430, 450, 430 and 415 kPa, respectively, with the maximum value attained with 0.5% HPPM addition as well. In contrast, the values of UVP at 0%, 0.5%, 1% and 2% are 978.5, 680.3, 489.4 and 323.6 m/s, respectively, confirming the trends obtained by modified compaction test results. The simulation results confirm this conclusion that the soil-HPPM mix show a superior performance when used as a subbase layer and reduced vertical displacement by a percentage of 11% compared to the normal subbase material. By eliminating HPPM especially facemasks from the landfill lifecycle, incorporating them into high quality construction material production has the potential to deliver significant environmental benefits.

Reconstitution of the core of the malaria parasite glideosome with recombinant Plasmodium class XIV myosin A and Plasmodium actin.

Motility of the apicomplexan malaria parasite Plasmodium falciparum is enabled by a multiprotein glideosome complex, whose core is the class XIV myosin motor, PfMyoA, and a divergent Plasmodium actin (PfAct1). Parasite motility is necessary for host-cell invasion and virulence, but studying its molecular basis has been hampered by unavailability of sufficient amounts of PfMyoA. Here, we expressed milligram quantities of functional full-length PfMyoA with the baculovirus/Sf9 cell expression system, which required a UCS (UNC-45/CRO1/She4p) family myosin chaperone from Plasmodium spp. In addition to the known light chain myosin tail interacting protein (MTIP), we identified an essential light chain (PfELC) that co-purified with PfMyoA isolated from parasite lysates. The speed at which PfMyoA moved actin was fastest with both light chains bound, consistent with the light chain-binding domain acting as a lever arm to amplify nucleotide-dependent motions in the motor domain. Surprisingly, PfELC binding to the heavy chain required that MTIP also be bound to the heavy chain, unlike MTIP that bound the heavy chain independently of PfELC. Neither the presence of calcium nor deletion of the MTIP N-terminal extension changed the speed of actin movement. Of note, PfMyoA moved filaments formed from Sf9 cell-expressed PfAct1 at the same speed as skeletal muscle actin. Duty ratio estimates suggested that as few as nine motors can power actin movement at maximal speed, a feature that may be necessitated by the dynamic nature of Plasmodium actin filaments in the parasite. In summary, we have reconstituted the essential core of the glideosome, enabling drug targeting of both of its core components to inhibit parasite invasion.

Neural correlates of subjective CS/UCS association in appetitive conditioning.

Explicit knowledge of conditioned stimulus (CS)/unconditioned stimulus (UCS) associations is proposed as important factor in classical conditioning. However, while previous studies have focused on its roles in fear conditioning, it has been neglected in the context of appetitive conditioning. The present functional magnetic resonance study aimed to investigate neural activation and functional connectivity linked to subjective CS/UCS association in appetitive conditioning. In total, 85 subjects participated in an appetitive acquisition procedure in which a neutral stimulus (CS+) was paired with a monetary reward, while another neutral stimulus (CS-) was never paired with the reward. Directly afterwards, subjective CS/UCS association was assessed by measuring the extent to which the CS+ was thought to be associated with the UCS compared to the CS-. Close relationships were established between subjective CS/UCS association and activations in the primary visual cortex (V1) during the early phase of conditioning and in the striatum during the late conditioning phase. In addition, we observed inverse relationships between subjective CS/UCS association and both V1/ventromedial prefrontal cortex (vmPFC) and striatal/vmPFC connectivity. The results suggest the involvement of decoupling vmPFC connectivity in reward learning in general and the roles of attentional processes in the formation of the subjective CS/UCS association during the early phase and reward prediction during the late phase of appetitive conditioning.

Psychotherapy.

This chapter focuses on psychotherapy of substance and non-substance addiction (see Cognitive Behavioral Therapy in Chap. 16 ) and introduces the latest advances, mainly in the mindfulness-based relapse prevention, PITDH, and points out that complete elimination of psychological addiction is hopefully to become the target and core of the psychotherapy of addiction disorder. This chapter also introduces methods and progress of various types of substance and non-substance addiction.

Periprosthetic fractures: epidemiology and current treatment.

Periprosthetic fractures are becoming increasingly frequent due to aging population and growing number of total joint replacements involving joints different from hip and knee, such as shoulder and elbow. The treatment of these fractures still represents one of the major challenges for the orthopedic surgeon. Despite all efforts to understand and treat these patients, high rate of failure and mortality are still reported. In this review, the epidemiology of periprosthetic fractures, risk factors and results of surgical treatment are disclosed. Moreover, we propose a treatment algorithm based on the findings of the New Unified Classification System.

A Toxoplasma gondii class XIV myosin, expressed in Sf9 cells with a parasite co-chaperone, requires two light chains for fast motility.

Many diverse myosin classes can be expressed using the baculovirus/Sf9 insect cell expression system, whereas others have been recalcitrant. We hypothesized that most myosins utilize Sf9 cell chaperones, but others require an organism-specific co-chaperone. TgMyoA, a class XIVa myosin from the parasite Toxoplasma gondii, is required for the parasite to efficiently move and invade host cells. The T. gondii genome contains one UCS family myosin co-chaperone (TgUNC). TgMyoA expressed in Sf9 cells was soluble and functional only if the heavy and light chain(s) were co-expressed with TgUNC. The tetratricopeptide repeat domain of TgUNC was not essential to obtain functional myosin, implying that there are other mechanisms to recruit Hsp90. Purified TgMyoA heavy chain complexed with its regulatory light chain (TgMLC1) moved actin in a motility assay at a speed of ∼1.5 µm/s. When a putative essential light chain (TgELC1) was also bound, TgMyoA moved actin at more than twice that speed (∼3.4 µm/s). This result implies that two light chains bind to and stabilize the lever arm, the domain that amplifies small motions at the active site into the larger motions that propel actin at fast speeds. Our results show that the TgMyoA domain structure is more similar to other myosins than previously appreciated and provide a molecular explanation for how it moves actin at fast speeds. The ability to express milligram quantities of a class XIV myosin in a heterologous system paves the way for detailed structure-function analysis of TgMyoA and identification of small molecule inhibitors.

Optimized kernel extreme learning machine using Sine Cosine Algorithm for prediction of unconfined compression strength of MICP cemented soil.

Microbially induced calcite precipitation (MICP) is an eco-friendly bio-remediation technology. The unconfined compressive strength (UCS) of MICP cemented soil is an important indicator of repair effectiveness. This study proposes a machine learning technique utilizing the Sine Cosine Algorithm (SCA) to optimize the regularization coefficient C and kernel width γ of the kernel extreme learning machine (KELM) to predict the UCS of MICP cemented soil. To evaluate the performance of the proposed models, a dataset containing 180 groups of the UCS of MICP cemented soil was obtained. The results obtained by SCA-KELM were compared with those obtained by the Random Forest algorithm (RF), Support Vector Machine (SVM), and KELM. The performance of these models was evaluated by the scores of MAE, RMSE, and R2. The results indicate that the SCA-KELM algorithm exhibits optimal prediction performance (Total score: 21). After optimizing KELM with SCA, the total score improved by 110%, suggesting that SCA significantly enhances the KELM performance. After model development, the optimal population size for SCA-KELM was determined to be 50. Based on the mutual information test, an innovative method was developed for categorizing factor sensitivity by employing importance scores as the partitioning criterion. This method categorizes the influencing factors into three tiers: high (importance score: 8.03-11.14%), medium (importance score: 5.93-7.25%), and low (importance score: 3.23-5.18%). These results suggest that the proposed SCA-KELM algorithm can be regarded as a powerful tool for predicting the UCS of MICP cemented soil.

Microcrystalline Cellulose-A Green Alternative to Conventional Soil Stabilizers.

Biopolymers are polymers of natural origin and are environmentally friendly, carbon neutral and less energy-intense additives that can be used for various geotechnical applications. Biopolymers like xanthan gum, carrageenan, chitosan, agar, gellan gum and gelatin have shown potential for improving subgrade strength, erosion resistance, and as canal liners and in slope stabilization. But minimal research has been carried out on cellulose-based biopolymers, particularly microcrystalline cellulose (MCC), for their application in geotechnical and geo-environmental engineering. In this study, the effect of MCC on select geotechnical properties of kaolin, a weak, highly compressible clay soil, like its liquid and plastic limits, compaction behavior, deformation behavior, unconfined compression strength (UCS) and aging, was investigated. MCC was used in dosages of 0.5, 1.0, 1.5 and 2% of the dry weight of the soil, and the dry mixing method was adopted for sample preparation. The results show that the liquid limit increased marginally by 11% but the plasticity index was nearly 74% higher than that of untreated kaolin. MCC rendered the treated soil stiffer, which is reflected in the deformation modulus, which increased with both dosage and age of the treated sample. The UCS of kaolin increased with dosage and curing period. The maximum UCS was observed for a dosage of 2% MCC at a 90-day curing period. The increase in stiffness and strength of the treated kaolin with aging points out that MCC can be a potential soil stabilizer.

Exploring the geotechnical and microstructural properties of composite mixtures for landfill liner materials: an experimental investigation.

The present study directs the need for the development of an economical composite mix comprised locally available soil and industrial waste which satisfy the design parameters of the municipal solid waste (MSW) landfill. The local soil, bentonite, and fly ash mixtures are mixed in different proportions to evaluate the geotechnical and microstructural characteristics for suggesting an optimum composite mix that fulfills the design parameters of landfill liners. The curing periods of different mixes are also considered while evaluating the unconfined compressive strength (UCS) characteristics. The microstructure of the mixtures is examined using advanced imaging techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDAX) to gain insights into the changes at the microscale level due to the inclusion of fly ash. It is observed that soil-bentonite-fly ash composite mix in a ratio of 65:15:20 aligns with the optimal design characteristics required for a landfill liner. Notably, for this composite mix, both liquid limit (LL) and plastic limit (PL) show a significant increase of 48.57% and 32.33% respectively, while the optimum moisture content (OMC) rises by 11.25%. Conversely, maximum dry density (MDD) experiences an 8.79% decrease. Moreover, the free swell index (FSI) escalates by 113%, whereas hydraulic conductivity (HC) records a substantial reduction of 96.04%. Moreover, the UCS exhibited a notable increase of 209% after a 28-day curing period. The highest strength is achieved initially by soil mixed with 20% fly ash, followed by a blend containing 15% bentonite. Therefore, proper fly ash content in filler and other binder materials is an effective and sustainable approach that not only solves the disposal issue but also enhances the material's engineering characteristics, justifying its suitability to be used as a landfill liner.

Geotechnical performance of black cotton clay in the presence of lead and cadmium solutions for geoenvironmental application.

The usage of bentonites and sand-bentonite mixtures as liners has become prevalent due to their low permeability. However, these materials are scarce and prohibitively expensive in India. Black cotton clay (BCC) was chosen as an alternative clay liner for this research due to its abundance in India and its mineralogical composition. Since heavy metals accumulation in municipal landfills is a rising issue with devastating effects on the ecosystem and human health, in this investigation, two heavy metals (lead and cadmium) were intended as permeants at three different concentrations (100, 500, and 1000 ppm) to imitate the impact of heavy metal leachate on BCC. The essential index and engineering properties of BCC were evaluated and compared under these two permeants from the liner perspective. Experimental results revealed that the free swell index, Atterberg limits, swelling and swelling pressures were reduced for a rise in concentration irrespective of metal type. However, this reduction was more with cadmium permeants compared to lead. The measured swelling data was compared with predicted swelling data using a rectangular hyperbola model, and a good correlation was achieved. The hydraulic conductivity (k) and unconfined compressive strength (UCS) values were increased for a rise in concentration with both metal permeants. At 1000 ppm concentration, the k values were raised to 3.5 and 6.7 times, and UCS values were enhanced by 8.3 and 5.5% for lead and cadmium permeants, respectively. At high concentrations, field emission scanning electron microscopy (FESEM) results showed the formation of huge voids and aggregation.

Experimental Study on Mechanical Properties of Recycled Aggregate Mixed Soil.

In the context of efforts aimed at reducing carbon emissions, the utilization of recycled aggregate soil mixes for soil stabilization has garnered considerable interest. This study examines the mechanical properties of mixed soil samples, varying by dosage of a soft soil curing agent C, recycled aggregate R content, and curing duration. Mechanical evaluations were conducted using unconfined compressive strength tests (UCS), field emission scanning electron microscopy (FESEM), and laser diffraction particle size meter tests (PSD). The results indicate that the strength of the mixed soil samples first increases and then decreases with higher dosages of recycled aggregate, reaching optimal strength at a 20% dosage. Similarly, an increase in curing agent dosage enhances the strength, peaking at 20%. The maximum strength of the mixed soils is achieved at 28 days under various proportions. The introduction of the curing agent leads to the formation of a flocculent structure, as observed in FESEM, which contributes to the enhanced strength of the soil mixes. Specimens prepared with a combination of 20% R and 20% C, maintained at a constant moisture content of 20%, and cured for 28 days exhibit a balance between economic, environmental, and engineering performance.

Development of empirical equations between uniaxial compressive strength and point load index: a case study for sandy dolomite.

In this research, the Yuxi section of Central Yunnan Water Diversion Project in Southwest of China, including the tunnel and the traversed sandy dolomite along its route, was selected as the research area, and different sandification degrees classification, including strongly sandy, medium sandy, and weakly sandy, were collected. A comprehensive suite of geotechnical tests was conducted, which included CT scanning, cathodoluminescence, density, porosity, softening coefficient, saturation coefficient, point load test, and uniaxial compressive strength (UCS) test. The Point load index (Is(50)) model for predicting UCS of different sandification degrees dolomite under dry and saturated conditions were analyzed by least square regression, and the empirical equation with correlation coefficient (R2) between 0.7372 and 0.8347 are obtained. To evaluate the performance of the prediction model, some statistical parameters, including MAE, MSE and RMSE, are calculated to evaluate the effectiveness of the empirical equation. The results of this study indicate that the point load test is one of the reliable methods for estimating the UCS of sandy dolomite under both dry and saturated conditions. Furthermore, the results of the point load test on sandy dolomite hold significant reference value for their practical application and promotion in the field, suggesting a broader utility in engineering practice.

Comparative study on convolutional neural network and regression analysis to evaluate uniaxial compressive strength of Sandy Dolomite.

Sandy Dolomite is a kind of widely distributed rock. The uniaxial compressive strength (UCS) of Sandy Dolomite is an important metric in the application in civil engineering, geotechnical engineering, and underground engineering. Direct measurement of UCS is costly, time-consuming, and even infeasible in some cases. To address this problem, we establish an indirect measuring method based on the convolutional neural network (CNN) and regression analysis (RA). The new method is straightforward and effective for UCS prediction, and has significant practical implications. To evaluate the performance of the new method, 158 dolomite samples of different sandification grades are collected for testing their UCS along and near the Yuxi section of the Central Yunnan Water Diversion (CYWD) Project in Yunnan Province, Southwest of China. Two regression equations with high correlation coefficients are established according to the RA results, to predict the UCS of Sandy Dolomites. Moreover, the minimum thickness of Sandy Dolomite was determined by the Schmidt hammer rebound test. Results show that CNN outperforms RA in terms of prediction the precision of Sandy Dolomite UCS. In addition, CNN can effectively deal with uncertainty in test results, making it one of the most effective tools for predicting the UCS of Sandy Dolomite.

Marble Powder as a Soil Stabilizer: An Experimental Investigation of the Geotechnical Properties and Unconfined Compressive Strength Analysis.

Fine-grained soils present engineering challenges. Stabilization with marble powder has shown promise for improving engineering properties. Understanding the temporal evolution of Unconfined Compressive Strength (UCS) and geotechnical properties in stabilized soils could aid strength assessment. This study investigates the stabilization of fine-grained clayey soils using waste marble powder as an alternative binder. Laboratory experiments were conducted to evaluate the geotechnical properties of soil-marble powder mixtures, including Atterberg's limits, compaction characteristics, California Bearing Ratio (CBR), Indirect Tensile Strength (ITS), and Unconfined Compressive Strength (UCS). The effects of various factors, such as curing time, molding water content, and composition ratios, on UCS, were analyzed using Exploratory Data Analysis (EDA) techniques, including histograms, box plots, and statistical modeling. The results show that the CBR increased from 10.43 to 22.94% for unsoaked and 4.68 to 12.46% for soaked conditions with 60% marble powder, ITS rose from 100 to 208 kN/m2 with 60-75% marble powder, and UCS rose from 170 to 661 kN/m2 after 28 days of curing, molding water content (optimum at 22.5%), and composition ratios (optimum at 60% marble powder). Complex modeling yielded R2 (0.954) and RMSE (29.82 kN/m2) between predicted and experimental values. This study demonstrates the potential of utilizing waste marble powder as a sustainable and cost-effective binder for soil stabilization, transforming weak soils into viable construction materials.

Mechanical properties and acoustic emission characteristics of basalt fiber reinforced cemented silty sand subjected to freeze-thaw cycles.

Freeze-thaw (F-T) cycling poses a significant challenge in seasonally frozen zones, notably affecting the mechanical properties of soil, which is a critical consideration in subgrade engineering. Consequently, a series of unconfined compressive strength tests were conducted to evaluate the influence of various factors, including fiber content, fiber length, curing time, and F-T cycles on the unconfined compression strength (UCS) of fiber-reinforced cemented silty sand. In parallel, acoustic emission (AE) testing was conducted to assess the AE characteristic parameters (e.g., cumulative ring count, cumulative energy, energy, amplitude, RA, and AF) of the same material under F-T cycles, elucidating the progression of F-T-induced damage. The findings indicated that UCS initially increased and then declined as fiber content increased, with the optimal fiber content identified at 0.2%. UCS increased with prolonged curing time, while increases in fiber length and F-T cycles led to a reduction in UCS, which then stabilized after 6 to 10 cycles. Stable F-T cycles resulted in a strength loss of approximately 30% in fiber-reinforced cemented silty sand. Furthermore, AE characteristic parameters strongly correlated with the stages of damage. F-T damage was segmented into three stages using cumulative ring count and cumulative energy. An increase in cumulative ring count to 0.02 × 104 times and cumulative energy to 0.03 × 104 mv·µs marked the emergence of critical failure points. A sudden shift in AE amplitude indicated a transition in the damage stage, with an amplitude of 67 dB after 6 F-T cycles serving as an early warning of impending failure.

Clinicopathological and molecular features of tubo-ovarian carcinosarcomas: a series of 51 cases.

Objective: Tubo-ovarian carcinosarcomas are rare, extremely aggressive malignant tumors that contain both carcinomatous and sarcomatous components. Due to the disease's rarity, developing an effective treatment strategy for ovarian carcinosarcomas has been challenging. A study was conducted to investigate the clinicopathologic and molecular features of this rare disease. Methods: We enrolled all patients diagnosed with tubo-ovarian carcinosarcomas from January 2007 to December 2022. The clinical and pathological data were gathered from medical records. Kaplan-Meier curves were plotted to calculate OS and PFS. The Log-rank test and Cox regression model were utilized to explore the relationship between clinicopathological parameters and survival. Patients with cancer tissues available had sequencing with a 242-gene panel done to investigate the mutational landscape and signature of the disease. Results: In total, 65% of the patients were diagnosed with advanced-stage cancer. The median PFS and OS of this cohort were 27 and 40 months, respectively, and there was no significant difference in survival between the homologous and heterologous components of sarcoma. Unexpectedly, staging did not have effects on prognosis. All patients had surgical attempts, and suboptimal debulking status was correlated with poorer PFS and OS. MSI was identified in 0% with low Tumor mutation burden (TMB) indicating a poor response to immunotherapy. Low HER2 expression is controversial, according to previous reports, and gives us limited choices with this rare and aggressive disease. We surprisingly found the homologous recombination deficiency (HRD)-positive status was identified in 64% of OCS, which is significantly higher than UCS and other types of epithelial ovarian cancer. The fact that all patients in our cohort who received olaparib as maintenance therapy had survived over 30 months and two had no evidence of recurrence at the latest follow-up might further validate the role of poly (ADP-ribose) polymerase inhibitors (PARPi) in the management of OCS. Conclusion: OCS patients seemed to respond to carboplatin/paclitaxel with optimal PFS and OS. Cytoreduction with no residuals proved to be the sole independent prognostic factor. WES should be done to assess the prognosis and assist with the targeted therapy, especially the HRD test, which might help select potential patients who benefit from PARPi.

Multi-objective genetic algorithm calibration of colored self-compacting concrete using DEM: an integrated parallel approach.

A detailed numerical simulation of Colored Self-Compacting Concrete (CSCC) was conducted in this research. Emphasis was placed on an innovative calibration methodology tailored for ten unique CSCC mix designs. Through the incorporation of multi-objective optimization, MATLAB's Genetic Algorithm (GA) was seamlessly integrated with PFC3D, a prominent Discrete Element Modeling (DEM) software package. This integration facilitates the exchange of micro-parameter values, where MATLAB's GA optimizes these parameters, which are then input into PFC3D to simulate the behavior of CSCC mix designs. The calibration process is fully automated through a MATLAB script, complemented by a fish script in PFC, allowing for an efficient and precise calibration mechanism that automatically terminates based on predefined criteria. Central to this approach is the Uniaxial Compressive Strength (UCS) test, which forms the foundation of the calibration process. A distinguishing aspect of this study was the incorporation of pigment effects, reflecting the cohesive behavior of cementitious components, into the micro-parameters influencing the cohesion coefficient within DEM. This innovative approach ensured significant alignment between simulations and observed macro properties, as evidenced by fitness values consistently exceeding 0.94. This investigation not only expanded the understanding of CSCC dynamics but also contributed significantly to the discourse on advanced concrete simulation methodologies, underscoring the importance of multi-objective optimization in such studies.

Investigation of constitutive properties of high plasticity clay soils mixed with crushed rubber tire waste.

Addressing the enormous waste resulting from discarded worn rubber tires is an environmental challenge. Recycling and using crushed rubber tire waste (CRTW) in construction materials can help in addressing this challenge. This study investigates the effect of addition of CRTW on the engineering properties of high plasticity clay soils (HPCS). There is a paucity of research in the application of CRTW in HPCS. This research tries to fill this research gap. Specifically, this study seeks to investigate the effect of mixing CRTW on the constitutive properties of HPCS. After identifying a locally available HPCS, mixtures of the clay and several percentages (0%, 6%, 12%, 18%, and 24%) by weight of CRTW were prepared. A range of CRTW shapes and sizes were investigated. Three different particle shapes of CRTW (granular rubber, rubber chips, and rubber fiber), and two particle sizes (fine and coarse) were studied. The parameters studied included unconfined compressive strength (UCS), strain at failure, post-peak strength loss (PPSL), modulus of elasticity, failure modes/mechanisms, repeatability of tests results, and examination of CRTW particles and mixtures via binocular and SEM microscope. Our findings unveiled that the highest level of repeatability was observed in granular CRTW, with a maximum variability of only 5%. Moreover, the mixtures containing granular CRTW exhibited, on average, 10% and 15% higher strength and modulus of elasticity, respectively, in comparison to mixtures incorporating other shapes of CRTW. In general, the HPCS-CRTW mixtures displayed higher shear strains, averaging 25% greater than pure HPCS. Furthermore, the addition of CRTW to HPCS resulted in a reduction of its PPSL and a transition in behavior from brittle to slightly ductile. Examination of failed specimens revealed the existence of two primary failure modes: shear plane failure and shear plane failure accompanied by multiple vertical cracks within the mixtures. These results suggest that the utilization of granular CRTW in HPCS can improve certain properties of HPCS. However, it is advisable to limit the rubber content in this mixture to 6% to mitigate significant adverse effects on its strength.