Global Response Research Articles

An IL-17-DUOX2 axis controls gastrointestinal colonization by Candida albicans.

Candida albicans is a ubiquitous fungus in the human gut microbiome as well as a prevalent cause of opportunistic mucosal and systemic disease. There is currently little understanding, however, as to how crosstalk between C. albicans and the host regulates colonization of this key niche. Here, we performed expression profiling on ileal and colonic tissues in germ-free mice colonized with C. albicans to define the global response to this fungus. We reveal that Duox2 and Duoxa2 , encoding dual NADPH oxidase activity, are upregulated in both the ileum and colon, and that induction requires the C. albicans yeast-hyphal transition and the hyphal-specific toxin candidalysin. Hosts lacking the IL-17 receptor failed to upregulate Duox2/Duoxa2 in response to C. albicans , while addition of IL-17A to colonoids induced these genes together with the concomitant production of hydrogen peroxide. To directly define the role of Duox2/Duoxa2 in fungal colonization, antibiotic-treated mice lacking intestinal DUOX2 activity were evaluated for C. albicans colonization and host responses. Surprisingly, loss of DUOX2 function reduced fungal colonization at extended time points (>17 days colonization) and increased the proportion of hyphal cells in the gut. IL-17A levels were also elevated in C. albicans -colonized mice lacking functional DUOX2 highlighting cross-regulation between this cytokine and DUOX2. Together, these experiments reveal novel links between fungal cells, candidalysin toxin and the host IL-17-DUOX2 axis, and that a complex interplay between these factors regulates C. albicans filamentation and colonization in the gut.

Similarity law of global and local responses of reinforced concrete beams subjected to impact loading

In the experiment of scaled models to dealing with the impact of reinforced concrete large structures, the strain rate hardening effect can lead to significant differences between the dynamic responses of prototype and model. In the present study, this thorny problem is solved by adjusting the impact velocity. Based on the mechanisms of different dynamic responses, the similarity laws for the global and local responses of reinforced concrete beams subjected to impact loading are proposed by considering the strain-rate effect of materials through Buckingham Π-theorem, where constitutive models of different materials are employed for inferring dynamic stress. In dimensional analysis, multiple control factors need to be considered simultaneously, such as the strain-rate effects of steel and concrete, since reinforced concrete components are typical composite structures. The similarity law cannot be unified when considering multiple control factors. In view of this, it is recommended to estimate the dynamic response of reinforced concrete components subjected to impact loading through the upper and lower bounds of similarity law. The upper bound of similarity law is based on the strain-rate effect of concrete, while the lower bound of similarity law is based on the strain-rate effect of steel bar. The numerical models of reinforced concrete beams are established based on the experimental background. The numerical simulations with different scaling factors indicate that the model modified by the lower bound of similarity law can better predict the global response of prototype, while the model modified by the upper bound of similarity law can more accurately predict the local response of prototype. In addition, the influence of dynamic elastic modulus of reinforced concrete on the similarity law is discussed through comparative analysis.

Network-based constraint to evaluate climate sensitivity

The 2015 Paris agreement was established to limit Greenhouse gas (GHG) global warming below 1.5°C above preindustrial era values. Knowledge of climate sensitivity to GHG levels is central for formulating effective climate policies, yet its exact value is shroud in uncertainty. Climate sensitivity is quantitatively expressed in terms of Equilibrium Climate Sensitivity (ECS) and Transient Climate Response (TCR), estimating global temperature responses after an abrupt or transient doubling of CO2. Here, we represent the complex and highly-dimensional behavior of modelled climate via low-dimensional emergent networks to evaluate Climate Sensitivity (netCS), by first reconstructing meaningful components describing regional subprocesses, and secondly inferring the causal links between these to construct causal networks. We apply this methodology to Sea Surface Temperature (SST) simulations and investigate two different metrics in order to derive weighted estimates that yield likely ranges of ECS (2.35–4.81°C) and TCR (1.53-2.60°C). These ranges are narrower than the unconstrained distributions and consistent with the ranges of the IPCC AR6 estimates. More importantly, netCS demonstrates that SST patterns (at “fast” timescales) are linked to climate sensitivity; SST patterns over the historical period exclude median sensitivity but not low-sensitivity (ECS < 3.0°C) or very high sensitivity (ECS ≥ 4.5°C) models.

Simple and effective mechanical cloaking

We show theoretically that essentially perfect elastostatic mechanical cloaking of a circular inclusion in a homogeneous surrounding medium can be achieved by means of a simple cloak comprising three concentric annuli, each formed of a homogeneous isotropic linear elastic material of prescribed shear modulus. Importantly, we find that the same combination of annuli will cloak any possible mode of imposed deformation or loading, for any randomly chosen admixture of imposed compression, pure shear and simple shear, without the need to re-design the cloak for different deformation modes. A full range of circular inclusions can be cloaked in this way, from soft to stiff. In consequence, we suggest that an inclusion of any arbitrary shape can also be cloaked, by first enveloping it in a stiff circle, then cloaking the combined structure with three annuli as described. Given that a single inclusion can be fully cloaked in this way, even at near field close to the cloaking perimeter, it also follows that multiple such neutral inclusions arranged with arbitrarily high packing fraction in a surrounding medium can also be cloaked. We confirm this by direct simulation. This indicates a possible route to fabricating composite materials with the same global mechanical response as a counterpart homogeneous material, and with uniform strain and stress fields outwith the cloaked inclusions.

Tower loads characteristics of a semi-submersible floating wind turbine: An experimental study

For a Floating Wind Turbine (FWT), the tower emerges as a critical structure that connecting the Rotor-Nacelle Assembly (RNA) and the supporting platform, facilitating the transmission of both aerodynamic and hydrodynamic loads. This paper deduces the distinct responses of the bending moment generated by the motion of a FWT compared with a fixed wind turbine. Due to the complexity of the tower load responses, a comprehensive experimental investigation was conducted on a semi-submersible FWT. Stiffness-matched and geometry-matched tower models were designed and fabricated. These models accurately simulate the tower's flexibility and windward areas, impacting the global dynamic response. The model test precisely replicates the marine environmental conditions, incorporating the interactions between wind, waves, and current. It is particularly worth noting that, a multi-fans large-scale Wind Generation System (WGS) with rectifier networks was improved and fabricated to provide a reliable wind field. Results indicate that the tower load responses under the conditions with wind exhibit distinct nP component characteristics. Notably, 1P and 3P responses dominate most tower load responses, with the 3P response typically increasing with wind speed. The extreme value of My.b (y-axis moment at tower-base) is approximately 10 times larger than that of My.t (y-axis moment at tower-top), signifying a significant magnitude difference and reflecting the response characteristics of the tower loads. And the responses of My.b and Fx.t (x-axis force at tower-top) at the natural frequency of pitch motion are notably suppressed by the aerodynamic damping effect of wind. Furthermore, Fx.b (x-axis force at tower-base) and My.b exhibit obvious responses at the natural frequency of pitch motion. As the wave height increases, the wave-frequency response of the tower base load also strengthens, but the high-frequency response still accounts for a certain proportion of energy in the tower top load.

Global response of soil biodiversity to climate and land use changes

Soil biodiversity (SB) is experiencing significant changes worldwide, yet its responses to climate and land use changes remain unclear. In light of this, we combined multiple environmental factors to construct a global SB dataset with a spatial resolution of 0.25° × 0.25° from 2000 to 2019. We determined that the global mean SB value was 0.66 during 2000–2019, and it slowly increased at a rate of 6.24 × 10−4/yr. The highest SB value (1.20) occurred within the Amazon Plain. Among the climate factors, temperature (T) was found to be responsible for the majority of the SB changes, accounting for approximately 40% of them. Compared to the results of other studies, our findings indicated that the SB increased across all types of land use and that urbanization had a positive impact on the increase in the SB. However, the most significant increase occurred in the pasture/range land. Precipitation (P) had similar effects on the SB in the pasture/range land and unmanaged grass/shrubland, while the areas with sparse or no vegetation experienced significant variations in temperature. These findings provide additional insights into the global pattern of SB and highlight the role of climate and land use changes in driving global and regional changes in SB.

HER2 Antibody-Drug Conjugates Are Active against Desmoplastic Small Round Cell Tumor.

Desmoplastic small round cell tumor (DSRCT) is a rare but highly aggressive soft tissue sarcoma that arises in the abdominopelvic cavity of young males. Since the discovery of EWSR1::WT1 fusion as the driver of DSRCT, no actionable genomic alterations have been identified, limiting disease management to a combination of surgery, chemotherapy, and radiation, with very poor outcomes. Herein, we evaluated ERBB2/HER2 expression in DSRCT as a therapeutic target. ERBB2/HER2 expression was assessed in clinical samples and patient-derived xenografts (PDX) using RNA sequencing, RT-qPCR, and a newly developed HER2 IHC assay (clone 29D8). Responses to HER2 antibody-drug conjugates (ADC)-trastuzumab deruxtecan (T-DXd) and trastuzumab emtansine-were evaluated in DSRCT PDX, cell line, and organoid models. Drug internalization was demonstrated by live microscopy. Apoptosis was evaluated by Western blotting and caspase activity assays. ERBB2/HER2 was detectable in DSRCT samples from patients and PDXs, with higher sensitivity RNA assays and improved IHC detectability using clone 29D8. Treatment of ERBB2/HER2-expressing DSRCT PDX, cell line, and organoid models with T-DXd or trastuzumab emtansine resulted in tumor regression. This therapeutic response was long-lasting in T-DXd-treated xenografts and was mediated by rapid HER2 ADC complex internalization and cytotoxicity, triggering p53-mediated apoptosis and growth arrest. Xenograft regression was associated with bystander payload effects triggering global tumor niche responses proportional to HER2 status. ERBB2/HER2 is a therapeutic target in DSRCT. HER2 ADCs may represent novel options for managing this exceptionally aggressive sarcoma, possibly fulfilling an urgent and historically unmet need for more effective clinical therapy.

Deep learning based method for predicting DNA N6-methyladenosine sites

DNA N6 methyladenine (6mA) plays an important role in many biological processes, and accurately identifying its sites helps one to understand its biological effects more comprehensively. Previous traditional experimental methods are very labor-intensive and traditional machine learning methods also seem to be somewhat insufficient as the database of 6mA methylation groups becomes progressively larger, so we propose a deep learning-based method called multi-scale convolutional model based on global response normalization (CG6mA) to solve the prediction problem of 6mA site. This method is tested with other methods on three different kinds of benchmark datasets, and the results show that our model can get more excellent prediction results.

A Novel Strategy for the Equivalent Frame Modelling of Masonry Arches in Historic Buildings: Application to a Case Study

ABSTRACT Equivalent frame (EF) methods are increasingly used to evaluate the global seismic response of historic masonry buildings. However, applying these methods to arched structures is challenging due to the lack of a standard EF strategy for masonry arches. This paper proposes a novel EF modelling solution for masonry arches in historic buildings subject to seismic actions. The proposed strategy, which consists in modelling arches as inclined hinged beams, is presented through the application to a case study, the Giuseppe Verdi Politeama Theatre in Carrara, Italy. Nonlinear static analyses were first performed on a finite element (FE) macro-model of a representative arch-pillar system found in the building. The numerical results in terms of damage mechanisms and capacity curves allowed the development of an EF modelling strategy for masonry arches. This strategy was then applied to a three-dimensional EF model of the Politeama Theatre to evaluate its global seismic response through nonlinear static analyses. The results demonstrated the effectiveness of the proposed strategy in accurately simulating the contribution of the arches in resisting horizontal actions.

B-Spline signature responses in structural change detection: method development

Damage detection is perhaps the most critical objective of structural health monitoring. Proper documentation of the progression of structural damage from onset to failure enables performance-based maintenance that mitigates risk and contains socioeconomic impact. Recently, damage detection methods that focus on change detection through analyses of the structural global response in the frequency or time domain have garnered attention due to their efficiency and accuracy. This work proposes a novel time-domain, nonparametric, data-driven change detection method. The time-domain B-Spline transfer function is defined as a signature time history response of the structure, referred to in this work as the B-Spline signature response (BSR). BSR may be computed directly through a physics-based simulation, or it be extracted in a discrete form from measurements of displacement, velocity, or acceleration time histories of structural response to any external excitation. The BSR is independent of loading, is a characteristic of the system, and captures the condition of the structure at the time of acquisition without the need for identifying structural properties. In this work, the fundamentals of the BSR concept are introduced first along with the process of extracting a BSR from structural responses to arbitrary excitations. Verification and validation studies are conducted based on computer simulations and laboratory testing and are discussed in detail. Subsequently, an approach is proposed to detect change through correlation of BSR signals acquired at different times during the monitoring period. Any changes in the intrinsic characteristics affecting the response cause BSR changes and correlation loss. The change detection methodology is demonstrated through computer simulations and experimental investigations. Initial parametric studies are conducted to investigate the suitability of the proposed approach to detect small structural changes. This article demonstrates the validity of the proposed method and establishes the framework for further development and case-specific applications.

Resistance and the regimen: The microthanatopolitics of Venezuelan antiretroviral scarcity and HIV drug adherence failures

The Venezuelan State does not provide adequate antiretroviral therapy (ART) for the population living with HIV, resulting in pharmaceutical scarcity, involuntary treatment pauses, and adherence failures. Such a situation may result in the development of resistance to certain ART drugs, meaning that Venezuelans with HIV may have their treatment options reduced for the remainder of their lives. It can take a number of years for a person to acquire late-stage HIV/AIDS and for death to occur, and so I focus on the microbiological death of CD4 cells over time – a concept I call ‘microthanatopolitics’.In this paper I argue that the microthanatopolitics of ART scarcity deprives those living with HIV of future treatment options, encourages resistance to ART drugs, and ultimately may contribute towards ill health long after treatment availability changes in Venezuela. To explore this in depth, the paper draws upon 6 interviews with Venezuelan HIV activists in Venezuela (2024), supported by 40 testimonies from Venezuelan migrants living with HIV in Colombia (2021–2024), with and without known ART resistance.It will be concluded that not only is this an issue for those currently living in Venezuela, but also for migrants and the global HIV response who will suffer from the promotion and circulation of ART-resistant viral strains in the long run. This microthanatopolitics is influenced by both the current Venezuela political system as well as humanitarian aid from the Global North; an important consideration of coloniality in post-colonial Latin America.

Legal, ethical and moral aspects of the fight against aids as a social dangerous disease

The scientific article examines the relevant regulatory framework for the development of legal, ethical and moral regulation in the fight against HIV/AIDS, and provides recommendations for improving medical treatment and control mechanisms. In the research work, a comparative analysis of domestic legal acts with international legal norms as the current legal basis for the fight against the AIDS epidemic is considered, and the directions for the adoption of the legislation and judicial practice of model countries in the field of medical law for the Republic of Azerbaijan are stated. Based on case studies and empirical research, the article provides an assessment of the challenges and opportunities for strengthening legal protection, especially for people living with HIV/AIDS, and legal mechanisms for increasing access to care and treatment. Also, innovative methods and strategies are explored to protect the rights of people suffering from HIV/AIDS, to protect against discrimination and stigmatization through the application of directly mentioned coping strategies, as well as to create more sensitive and effective treatment mechanisms of the health care system. It is proposed to refine the legislation of the Republic of Azerbaijan and eliminate the loopholes in the law. Overall, the article emphasizes the importance of a strong legal framework for the development of the fight against AIDS and suggests practical steps to bring it to the agenda in today’s world. In the context of the ongoing global struggle against HIV/AIDS, our research emphasized the crucial role of legal regulation in the development of a comprehensive care system for individuals affected by this disease. The article underscored the significance of legal frameworks in ensuring unhindered access to care, treatment, and support for individuals living with HIV/AIDS. By establishing guidelines and standards for healthcare providers, legal regulation enables the delivery of high-quality care while safeguarding the rights of individuals affected by HIV/AIDS. Furthermore, the rule of law plays a vital role in combating stigma and discrimination, which remain significant obstacles to effective efforts to prevent and treat HIV/AIDS. It is also highlighted various tools and strategies for improving care for individuals living with HIV/ AIDS, including the integration of HIV services into existing healthcare systems, community-based care models, and the promotion of holistic and patient-centered approaches to care. In conclusion, our research demonstrates that legal regulation is a vital component of the global response to HIV/AIDS, as it enables the provision of comprehensive care and support to individuals affected by this disease. Moreover, the implementation of innovative care models and strategies outlined in international legal instruments can further enhance the quality and effectiveness of HIV/AIDS treatment services.

Global Dynamic Responses and Progressive Failure of Submerged Floating Tunnel Under Cable Breakage Conditions

Global Dynamic Responses and Progressive Failure of Submerged Floating Tunnel Under Cable Breakage Conditions

A Systematic Literature Review on the Composition, Health Impacts, and Regulatory Dynamics of Vaping.

This comprehensive review deals with the multifaceted aspects of electronic cigarettes (e-cigarettes), examining their composition, health implications, regulatory challenges, and market dynamics. E-cigarettes, also known as vaping devices, function by warming a solution of liquid containing flavors, nicotine, and various other compounds to produce an aerosol for users to inhale. This review underscores the evolution and widespread adoption of e-cigarettes since their introduction in 2003, highlighting their appeal as alternatives to traditional tobacco smoking. The essential parts of e-cigarettes are the battery, heating element, e-liquid (or e-juice), and mouthpiece. Propylene glycoland vegetable glycerinare common ingredients in e-liquids, along with nicotine and other flavors. Concerns over the health impacts of e-cigarettes have grown, particularly in light of incidents like the e-cigarette or vaping-associated lung injuryoutbreak in 2019 linked to vaping-associated lung injuries. Evidence suggests that while e-cigarettes may pose fewer risks than conventional cigarettes, they are not without health consequences, including potential respiratory and cardiovascular effects. Regulatory efforts worldwide have struggled to keep pace with the rapid evolution of e-cigarettes, exacerbated by their diverse flavors and marketing strategies that appeal to youth. The review discusses global regulatory responses, including bans and restrictions, to curb youth uptake and address public health concerns. Furthermore, the rise of a black market for e-cigarettes poses additional challenges to effective regulation and tobacco control efforts. In conclusion, while e-cigarettes offer potential harm reduction benefits for adult smokers seeking alternatives to traditional tobacco products, their widespread availability and evolving landscape necessitate vigilant regulatory oversight to protect public health, especially among youth. Future research should continue to explore the long-term health impacts and efficacy of e-cigarettes as smoking elimination aids, informing evidence-based policies and interventions.

Global distribution pattern of soil phosphorus-cycling microbes under the influence of human activities.

Human activities have profoundly altered the Earth's phosphorus (P) cycling process and its associated microbial communities, yet their global distribution pattern and response to human influences remain unclear. Here, we estimated the abundances of P-cycling genes from 3321 global soil metagenomic samples and mapped the global distribution of five key P-cycling processes, that is, organic phosphoester hydrolysis, inorganic phosphorus solubilization, two-component system, phosphotransferase system, and transporters. Structural equation modeling and random forest analysis were employed to assess the impact of anthropogenic and environmental factors on the abundance of P-cycling genes. Our findings suggest that although less significant than the climate and soil profile, human-related factors, such as economic activities and population, are important drivers for the variations in P-cycling gene abundance. Notably, the gene abundances were increased parallel to the extent of human intervention, but generally at low and moderate levels of human activities. Furthermore, we identified critical genera, such as Pseudomonas and Lysobacter, which were sensitive to the changes in human activities. This study provides insights into the responses of P-cycling microbes to human activities at a global scale, enhancing our understanding of soil microbial P cycling and underscoring the importance of sustainable human activities in the Earth's biogeochemical cycle.

Measuring thermomechanical response of large-format printed polymer composite structures via digital image correlation

Large-format additive manufacturing (LFAM) is a branch of additive manufacturing (AM) research with the ability to create large structures typically measuring several meters in scale. LFAM is advantageous for tooling applications, not only because it offers the ability to create complex geometries not easily made using subtractive manufacturing processes, but the cost savings of pelletized feedstock used by these systems result in larger parts printed at faster speeds than traditional AM systems. Fiber reinforced polymer (FRP) is a commonly used feedstock material in LFAM structures because it reduces the distortion experienced during printing. However, FRP introduces highly anisotropic thermomechanical properties and contributes to a nonhomogeneous microstructure that can result in critical distortion of dimensions during tooling. Measuring the global thermomechanical response of LFAM structures requires a more representative method that accounts for not only anisotropic properties but also the nonhomogeneous nature of the final part. This is where traditional techniques to measure thermomechanical response, such as thermomechanical analysis (TMA), fall short as they assume homogeneity. This study evaluated the coefficient of thermal expansion (CTE) of LFAM structures as measured by TMA as compared to a novel digital image correlation oven (DIC Oven) system. The LFAM structures were made from 20 % by weight carbon fiber reinforced acrylonitrile butadiene styrene (CF-ABS). TMA measurements showed significant variations in CTE across a single LFAM bead, confirming the need for a global technique that captures overall thermomechanical response. The CTE values measured using the DIC Oven compared well to average TMA values obtained from localized measurements across the sample. The DIC Oven was also used to quantify the effects of different layer orientations on thermomechanical properties, which cannot be easily captured using TMA. A predictive model was also developed by using localized TMA values across an LFAM bead to predict the overall thermomechanical response of an LFAM structure.

Global Response to Continuing Education Needs in Pediatrics; A Survey Study

Abstract Date Presented 03/21/24 As a needs assessment to provide pediatric professional development, this survey asked OTs (N=143) across the globe (32 countries represented) in what areas they need continuing education. The majority (70%) of OTs requested education in feeding. Primary Author and Speaker: Kate Barlow Additional Authors and Speakers: Said Nafai, Kathryn LeMonda, Allyson Bates Contributing Authors: Liliya Todorova, Marinela Rata, Petya Mincheva

Phase I/II clinical trial of brentuximab vedotin for pretreated Japanese patients with CD30-positive cutaneous T-cell lymphoma.

Brentuximab vedotin (BV), a conjugate of anti-CD30 antibody and monomethyl auristatin E, has emerged as a promising treatment option for refractory CD30+ mycosis fungoides (MF) and primary cutaneous anaplastic large-cell lymphoma (pcALCL). BV has been shown to be safe and effective in treating Hodgkin's lymphoma and peripheral T-cell lymphoma. This multicenter, prospective, single-arm phase I/II study evaluated the efficacy of BV in Japanese patients with CD30+ cutaneous lymphomas, namely CD30+ cutaneous T-cell lymphoma. Participants were divided into two groups: those with CD30+ MF or pcALCL (cohort 1, n = 13) and those with CD30+ lymphoproliferative disorders other than those in cohort 1 (cohort 2, n = 3). The studied population included the full analysis set (FAS), modified FAS (mFAS), and safety analysis set (SAF). These sets were identified in cohorts 1 and 1 + 2 and labeled FAS1 and FAS2, mFAS1 and mFAS2, and SAF1 and SAF2, respectively. Each treatment cycle lasted 3 weeks, and BV was continued for up to 16 cycles after the third cycle based on treatment response. The primary endpoint was the 4-month objective response rate (ORR4) determined by the Independent Review Forum (IRF). ORR4 was 69.2% for FAS1 and 62.5% for FAS2 (P < 0.0001). Secondary endpoints of ORR, assessed using the global response score (53.8% in FAS1) and modified severity-weighted assessment tool (62.5% in FAS1), using the IRF, provided results comparable to the primary findings. The incidence of ≥grade 3 adverse events (≥15%) in SAF1 was peripheral neuropathy in three patients (23%) and fever and eosinophilia in two patients (15%). In conclusion, BV showed favorable efficacy, tolerability, and safety profile in Japanese patients with relapsed or refractory CD30+ primary cutaneous T-cell lymphoma. The trial was registered with University Hospital Medical Information Network Clinical Trials Registry, Japan (protocol ID: UMIN000034205).

Global equity, commodities and bond market response to Israel-Hamas war

This study used event study methodology to examine the impact of Hamas’ terrorist attack against Israel in global equity, commodities, and bond markets. The results show that negative abnormal returns in global equity markets are limited to the Middle East region. The major world economies - China, Europe and the US, present insignificant abnormal returns. The increase in geopolitical risk, however, brings good news for commodities and bonds that observe significant positive abnormal returns with the intensification of the conflict. This result means that bonds and commodities are a hedge against stocks on average and a safe haven against conflict risk.

An alternative modeling approach to incorporate bond-slip effects in fiber-based elements

Fiber-based elements can provide accurate estimates of the global and local inelastic response of RC members subjected to reversed cyclic loads. However, fiber-based elements per se do not account for the localized deformations that arise from strain penetration or bond-slip effects at the member ends. To account for bond-slip effects, some researchers have suggested the use of modified properties for the steel reinforcement fibers, or that a zero-length element be attached at the element ends. In this study, a modified modeling procedure is proposed to include anchorage-slip effects in reinforced concrete frame members modeled with fiber-based beam-column elements. The proposed modeling approach is based on local bond-slip laws that can be implemented in general-purpose fiber-element software, and it differs from existing approaches in that it does not require the use of a zero-length element (though it could be used), and that it can be used with any local bond-slip relationship representative of a variety of bar embedment conditions. As such, the model can be used to simulate the effects of bond-slip of short or long embedment lengths in confined or unconfined concrete. The proposed modeling procedure is validated by comparing the calculated response with experimental data from four independent investigations. The test data included three columns and two beam specimens with various confinement and reinforcement configurations and included members reinforced with conventional and high-strength steel reinforcement. The results from the analyses show that the proposed modeling procedure provides a very good estimate of both the global and the local responses (anchorage-slip rotation) of the specimens.