Hot-spot Cell Research Articles

Expression of CD25, mast cell markers and T-cell markers in eosinophilic esophagitis

While eosinophilic esophagitis (EOE) is defined by histologic presence of eosinophils, a few studies have established the presence of mast cells in EOE and even shown their correlation with symptom persistence despite resolution of eosinophils. Expression of aberrant mast cell markers CD25 and CD2 have not been studied in EOE. This study quantifies the number of hotspot cells per high power field expressing CKIT/CD117, tryptase, CD25, CD2 and CD3 by immunohistochemical stains in endoscopic esophageal biopsies of the following three cohorts: (1) established and histologically confirmed EOE, (2) suspected EOE with biopsies negative for eosinophils, and (3) no history of or suspicion for EOE with histologically unremarkable biopsies. In this study, mast cells were highlighted by CKIT and tryptase in EOE, and not seen in other clinically mimicking cases. There were also significantly higher densities of CD25 and pan-T-cell marker staining in EOE cases. These findings suggest an inflammatory cellular milieu in EOE, beyond just eosinophils, that can be demonstrated by immunohistochemistry, and that invite further study into the role that these cells may play in EOE.

Hot Spot Detection of Photovoltaic Module Based on Distributed Fiber Bragg Grating Sensor

The hot spot effect is an important factor that affects the power generation performance and service life in the power generation process. To solve the problems of low detection efficiency, low accuracy, and difficulty of distributed hot spot detection, a hot spot detection method using a photovoltaic module based on the distributed fiber Bragg grating (FBG) sensor is proposed. The FBG sensor array was pasted on the surface of the photovoltaic panel, and the drift of the FBG reflected wavelength was demodulated by the tunable laser method, wavelength division multiplexing technology, and peak seeking algorithm. The experimental results show that the proposed method can detect the temperature of the photovoltaic panel in real time and can identify and locate the hot spot effect of the photovoltaic cell. Under the condition of no wind or light wind, the wave number and variation rule of photovoltaic module temperature value, environmental temperature value, and solar radiation power value were basically consistent. When the solar radiation power fluctuated, the fluctuation of hot spot cell temperature was greater than that of the normal photovoltaic cell. As the solar radiation power decreased to a certain value, the temperatures of all photovoltaic cells tended to be similar.

Research on hot spot risk of high wattage solar modules

With the rapid increase of solar module wattage from about 300 W to above 650 W, it is important to study the impact of high wattage on the hot spot risk. In this paper we use finite element analysis (FEA) and experiments to analyze the effects of various designs on the hot spot temperature of high wattage solar modules. Design factors include cell size (156.75 mm, 166 mm, 182 mm and 210 mm), the number of cells per bypass diode and cell shape (full cell, half cell and one-third cells). The simulation data is in good agreement with the experiment, and shows a clear trend: increasing the number of cells per bypass diode increases the hotspot temperature at most, increasing cell size leads to a moderate but considerate increase, and cutting a cell into smaller pieces lowers the hot spot temperature under certain conditions. The developed thermal balance model shows that the change in the power density and effective thermal resistance at the hotspot cells are the keys to the trend. This research proves the effectiveness of using finite element analysis (FEA) to study the hotspot risk, and points out a new direction for how to control the hotspot risk of high wattage solar modules with larger solar cells.

Perigenual and Subgenual Anterior Cingulate Afferents Converge on Common Pyramidal Cells in Amygdala Subregions of the Macaque.

The subgenual (sgACC) and perigenual (pgACC) anterior cingulate are important afferents of the amygdala, with different cytoarchitecture, connectivity, and function. The sgACC is associated with arousal mechanisms linked to salient cues, whereas the pgACC is engaged in conflict decision-making, including in social contexts. After placing same-size, small volume tracer injections into sgACC and pgACC of the same hemisphere in male macaques, we examined anterogradely labeled fiber distribution to understand how these different functional systems communicate in the main amygdala nuclei at both mesocopic and cellular levels. The sgACC has broad-based termination patterns. In contrast, the pgACC has a more restricted pattern, which was always nested in sgACC terminals. Terminal overlap occurred in subregions of the accessory basal and basal nuclei, which we termed "hotspots." In triple-labeling confocal studies, the majority of randomly selected CaMKIIα-positive cells (putative amygdala glutamatergic neurons) in hotspots received dual contacts from the sgACC and pgACC. The ratio of dual contacts occurred over a surprisingly narrow range, suggesting a consistent, tight balance of afferent contacts on postsynaptic neurons. Large boutons, which are associated with greater synaptic strength, were ∼3 times more frequent on sgACC versus pgACC axon terminals in hotspots, consistent with a fast "driver" function. Together, the results reveal a nested interaction in which pgACC ("conflict/social monitoring") terminals converge with the broader sgACC ("salience") terminals at both the mesoscopic and cellular level. The presynaptic organization in hotspots suggests that shifts in arousal states can rapidly and flexibly influence decision-making functions in the amygdala.SIGNIFICANCE STATEMENT The subgenual (sgACC) and perigenual cingulate (pgACC) have distinct structural and functional characteristics and are important afferent modulators of the amygdala. The sgACC is critical for arousal, whereas the pgACC mediates conflict-monitoring, including in social contexts. Using dual tracer injections in the same monkey, we found that sgACC inputs broadly project in the main amygdala nuclei, whereas pgACC inputs were more restricted and nested in zones containing sgACC terminals (hotspots). The majority of CaMKIIα + (excitatory) amygdala neurons in hotspots received converging contacts, which were tightly balanced. pgACC and sgACC afferent streams are therefore highly interdependent in these specific amygdala subregions, permitting "internal arousal" states to rapidly shape responses of amygdala neurons involved in conflict and social monitoring networks.

Tumour budding and CD8+ T cells: ‘attackers’ and ‘defenders’ in rectal cancer with and without neoadjuvant chemoradiotherapy

Tumour budding ('attacker') and CD8+ T cells ('defender') are recognised as important parameters for risk stratification in colon cancers and, combined, may have an even stronger clinical impact. Here, we determine the value of tumour budding and CD8+ in rectal cancer patients treated with/without neoadjuvant therapy. Using digital scans of all tumour slides/case, we analysed CD8+ T cell counts in two patient cohorts: 45 neoadjuvantly treated and 47 primarily surgically treated (totalling n=543 slides) after double-staining of the surgical resection specimen for pan-cytokeratin and CD8+ . Tumour buds in hot-spots were manually counted (area=0.785mm2 ) and CD8+ T cell counts were analysed separately both in tumour budding hot-spots and the densest CD8+ regions throughout the tumour. In neoadjuvantly treated patients, only tumour budding and not CD8+ T cells was associated with tumour features, including more advanced ypT (P=0.0062), venous invasion (P=0.002), lymphatic invasion (P=0.0003) and perineural invasion (P=0.0017), as well as higher American Joint Committee on Cancer (AJCC) tumour regression score (P=0.0035), indicating less tumour response. Overall survival was also worse in patients with high-grade budding in univariate analysis only. In contrast, all three variables, namely tumour budding (P=0.0347), CD8+ T cells in budding hot-spots (P=0.0382) and CD8+ T cells in the densest areas (P=0.0117) were also associated with worse (budding) and better (CD8) survival time in the multivariate setting. In rectal cancer, tumour budding has clinical relevance in both primarily surgically treated patients and in those with neoadjuvantly treated patients, where it characterises highly aggressive residual disease. CD8+ T cell counts appear not to have prognostic relevance in the neoadjuvant context.

Interobserver concordance in visual assessment of Ki67 immunohistochemistry in surgical excision specimens from patients with lymph node-negative breast cancer.

This study aimed to determine the interobserver concordance of two methods for proliferation assessment in breast cancer using Ki67 immunohistochemistry. Ki67 was independently assessed in randomly selected tumour samples from patients with lymph node-negative breast cancer using two different methods: either cell counting or visual estimation of hot spot areas. For hot spot cell counting, positive and negative cell numbers were recorded for total cell counts of 300-500, 500-800 and 800-1000 cells. Visual estimation involved allocation of a score from 1 to 5 using a visual scale to estimate percentage positivity. Interobserver agreement for hot spot counting was calculated using a two-way fixed effects intraclass correlation model, and by using Cohen's kappa measure for visual assessment. Prognostic concordance between the two methods was also calculated using Cohen's kappa. Samples from 96 patients were included in this analysis. Interobserver agreement for hot spot cell counting was excellent (> 0.75) across all three cell count ranges, with correlation coefficients of 0.88 (95% CI 0.84-0.92), 0.87 (95% CI 0.82-0.91) and 0.89 (95% CI 0.85-0.92), respectively. Interobserver agreement with visual estimation was greatest for hot spots compared with areas of intermediate or low proliferation, with kappa scores of 0.49, 0.42 and 0.40, respectively. Both assessment methods demonstrated excellent prognostic agreement. Interobserver and prognostic concordance in Ki67 immunohistochemistry assessments was high using either hot spot cell counting or visual estimation, further supporting the utility and reproducibility of these cost-efficient methods to assess proliferation.

Hot-spot generation model using electrical and thermal equivalent circuits for a copper indium gallium selenide photovoltaic module

Hot-spot generation is critical to the reliability and performance of copper indium gallium selenide (CIGS) solar cells; however, its occurrence mechanism has not been fully elucidated. We conducted a partial shade stress test on three large-area CIGS modules (156 cm × 62.6 cm in size, with 102 cells) connected in series. Partial shade stress can cause irreversible and unpredictable damage to the modules, and we confirmed the generation of hot spots on the shaded cells via infrared imaging. To emulate numerically the internal electrical and thermal changes in the shaded cells, we present electrical and thermal equivalent circuits based on the material properties and layered structure of the CIGS cells and modules. Furthermore, we propose a hot-spot generation model describing the irreversible damage to CIGS cells via shunt resistance degradation because the dissipated electrical power exceeds the threshold power (Pth). The current–voltage characteristics simulated by the presented method are congruent with those measured under partial shade conditions. Partial shade induces high electrical power consumption in the shaded cells, up to ~34 mW/cm2 at a 5% shade ratio, ~1,500 times higher than that in the unshaded cells. The shunt resistance is degraded to ~18.5 Ω/mm2 (only ~0.1% of the initial normal value), and the Pth-value is estimated to be ~2.4 mW/cm2 at the center of the hot-spot cells. The presented method and Pth-parameter can be used to evaluate durability with respect to the effects of partial shade stress for CIGS and various other thin-film photovoltaic cells and modules.

Multicellular "hotspots" harbor high-grade potential in lower-grade gliomas.

BackgroundLower-grade gliomas may be indolent for many years before developing malignant behavior. The mechanisms underlying malignant progression remain unclear.MethodsWe collected blocks of live human brain tissue donated by people undergoing glioma resection. The tissue blocks extended through the peritumoral cortex and into the glioma. The living human brain tissue was cut into ex vivo brain slices and bathed in 5-aminolevulinic acid (5-ALA). High-grade glioma cells avidly take up 5-ALA and accumulate high levels of the fluorescent metabolite, Protoporphyrin IX (PpIX). We exploited the PpIX fluorescence emitted by higher-grade glioma cells to investigate the earliest stages of malignant progression in lower-grade gliomas.ResultsWe found sparsely distributed “hot-spots” of PpIX-positive cells in living lower-grade glioma tissue. Glioma cells and endothelial cells formed part of the PpIX hotspots. Glioma cells in PpIX hotspots were IDH1 mutant and expressed nestin suggesting they had acquired stem-like properties. Spatial analysis with 5-ALA-conjugated quantum dots indicated that these glioma cells replicated adjacent to blood vessels. PpIX hotspots were formed in the absence of angiogenesis.ConclusionOur data show that PpIX hotspots represent microdomains of cells with high-grade potential within lower-grade gliomas and identify locations where malignant progression could start.

Ki-67 Index of 55% Distinguishes Two Groups of Bronchopulmonary Pure and Composite Large Cell Neuroendocrine Carcinomas with Distinct Prognosis

Background: Little information is available concerning prognostic factors for bronchopulmonary large cell neuroendocrine carcinomas (BP-LCNECs) and even less is known about combined LCNECs (Co-LCNECs). We investigated whether an integrated morphological, immunohistochemical, and molecular approach could be used for their prognostic evaluation. Methods: Morphological (including combined features), proliferative (mitotic count/Ki-67 index), immunohistochemical (napsin A, p40, TTF-1, CD44, OTP, SSTR2A, SSTR5, mASH1, p53, RB1, and MDM2), and genomic (TP53, RB1, ATM, JAK2, KRAS, and STK11) findings were analyzed in BP-LCNECs from 5 Italian centers, and correlated with overall survival (OS). The Ki-67 index was expressed as the percentage of positive cells in hot spots as indicated in the WHO 2019 Digestive System Tumors and, for Co-LCNECs, the Ki-67 index was evaluated only in the LCNEC component. Results: A total of 111 LCNECs were distinguished into 70 pure LCNECs, 35 Co-LCNECs (27 with adenocarcinoma [ADC] and 8 with squamous cell carcinoma [SqCC]), and 6 LCNECs with only napsin A immunoreactivity. The Ki-67 index cutoff at 55% evaluated in the neuroendocrine component was the most powerful predictor of OS (log-rank p = 0.0001) in all LCNECs; 34 cases had a Ki-67 index <55% (LCNEC-A) and 77 had a Ki-67 index ≥55% (LCNEC-B). Statistically significant differences in OS (log-rank p = 0.0001) were also observed between pure and Co-LCNECs. A significant difference in OS was found between pure LCNECs-A and Co-LCNECs-A (p < 0.05) but not between pure LCNECs-B and Co-LCNECs-B. Co-LCNEC-ADC and LCNEC napsin A+ cases had longer OS than pure LCNEC and Co-LCNEC-SqCC cases (log-rank p = 0.0001). On multivariable analysis, tumor location, pure versus combined features, and napsin A, but no single gene mutation, were significantly associated with OS after adjustment for Ki-67 index and study center (p < 0.05). Conclusions: The Ki-67 proliferation index and the morphological characterization of combined features in LCNECs seem to be important tools for predicting clinical outcome in BP-LCNECs.

Coverage Analysis of Integrated Sub-6GHz-mmWave Cellular Networks With Hotspots

Deploying Sub-6GHz networks together with millimeter wave (mmWave) is a promising solution to achieve high data rates in traffic hotspots while guaranteeing sufficient coverage, where mmWave small cells are densely deployed to provide high quality of service. In this paper, we propose an analytical framework to investigate the integrated Sub-6GHz-mmWave cellular networks, in which the Sub-6GHz base stations (BSs) are modeled as a Poisson point process, and the mmWave BSs are clustered following a Poisson cluster process in traffic hotspots. We conduct stochastic geometry-based analysis and derive the performance metrics including the association probability, signal-to-interference-plus-noise ratio coverage probability and average achievable rate, which are validated to be accurate by Monte Carlo simulations. We analyze the impact of various deployment parameters on the network performance to give insights on the network design. In particular, it is shown that deploying mmWave small cells in traffic hotspots will outperform both traditional Sub-6GHz heterogeneous network and isolated mmWave system in terms of the coverage probability. It can also be shown that extremely high and extremely small association weight for mmWave BSs will deteriorate the performance for cell edge users and cell interior users, respectively. Moreover, there exists an optimal pre-decided dispersion parameter of mmWave BSs that contributes to the maximum coverage probability.

Precoding for Flexible High Throughput Satellites: Hot-Spot Scenario

Motivated by the need of resource flexibility in high throughput satellite systems, a hot-spot cell configuration is introduced and analyzed in terms of throughput performance. Cell partitioning and user scheduling are also addressed in conjunction with the application of different types of linear precoding algorithms. The analysis is based on a real satellite system design and uses a system simulation approach, encompassing the random user distribution inside the hot-spot cell area. Results provide guidelines on the design of the hot-spot cell partitioning and show the achievable gains of precoding with respect to conventional, non precoded, transmission.

Dynamic self-reconfiguration of unmanned aerial vehicles to serve overloaded hotspot cells

Unmanned Aerial Vehicle (UAV) networks can provide wireless coverage to users when cellular infrastructure is unavailable. Each UAV covers a circular area, called a hotspot cell, and serves the users in it. Natural disasters can cause unpredictable mobility of users, randomly overloading some cells, called hot zones, for different time intervals. Along with an efficient initial deployment, this paper presents a two-fold approach to handle hot zones. First, the loads in overlapped sections are redistributed to neighbors. Second, a distributed algorithm is run that dynamically repositions the least number of UAVs to serve the maximum possible users. Additionally, to balance the user demand and supply of wireless coverage, adjacent UAVs are allowed to swap their positions. Simulation results show improvement in the network performance using the parameters: packet delivery ratio, data served per unit of depleted energy, service discontinuity time, and the total amount of data served.

Risks of Biological Invasion on the Belt and Road

China's Belt and Road Initiative (BRI) is an unprecedented global development program that involves nearly half of the world's countries [1]. Itnot only will have economic and political influences, but also may generate multiple environmental challenges and is a focus of considerable academic and public concerns [2-6]. The Chinese government expects BRI to be a sustainable development, paying equal attention to economic development and environmental conservation [7].However, BRI's high expenditure on infrastructure construction, by accelerating trade andtransportation, is likely to promote alien species invasions [5], one of the primary anthropogenic threats to global biodiversity [8]. BRI countries may have different susceptibilities to invasive species due to different financial and response capacities [9]. Moreover, these countries overlap 27 of 35 recognized global biodiversity hotspots [10]. Identifying those areas with high-invasionrisks, and species with high invasive potentials within BRI countries, is therefore of vital importance for the sustainable implementation of the BRI, and the development of early, economical, and effective biosecurity strategies [11]. In response, we present here a comprehensive study to evaluate invasion risks by alien vertebrates within BRI. We identified a total of 14 invasion hotspots, the majority of which fall along the six proposed BRI economic corridors, with the proportion of grid cells in invasion hotspots 1.6 times higher than other regions. Based on our results, we recommend the initiation of a project targeting early prevention, strict surveillance, rapid response, and effective control of alien species in BRI countries to ensure that this development is sustainable.

Optimizing utilization in cellular radio networks using mobility data

The main resource for any telecom operator is the physical radio cell network. We present two related methods for optimizing utilization in radio networks: Tetris optimization and selective cell expansion. Tetris optimization tries to find the mix of users from different market segments that provides the most even load in the network. Selective cell expansion identifies hotspot cells, expands the capacity of these radio cells, and calculates how many subscribers the radio network can handle after the expansions. Both methods are based on linear programming and use mobility data, i.e., data defining where different categories of subscribers tend to be during different times of the week. Based on real-world mobility data from a region in Sweden, we show that Tetris optimization based on six user segments made it possible to increase the number of subscribers by 58% without upgrading the physical infrastructure. The same data show that by selectively expanding less than 6% of the cells we are able to increase the number of subscribers by more than a factor of three without overloading the network. We also investigate the best way to combine Tetris optimization and selective cell expansion.

Comparison of Half-Cell and Full-Cell Module Hotspot-Induced Temperature by Simulation

The impact of partial shading on cell operating current, voltage, and temperature is simulated, for a half-cell module with series–parallel–series connections and for the conventional full-cell module. When shaded, we find the half-cell modules comprising two parallel 60-half-cell strings benefit from a reduced heat dissipation compared to a 60-full-cell series connected design. The maximum hotspot cell temperature of the shaded half-cell module is 28 °C lower than that of the full-cell module. Our result suggests that half-cell module design could mitigate hotspot degradation or failure in crystalline-silicon photovoltaic modules.

Prognostic Significance of Epidermal Growth Factor Receptor in Patients of Glioblastoma Multiforme.

Glioblastoma Multiforme (GBM) is the most aggressive glial tumour with hallmark characteristics of rampant proliferation of glial cells along with high pleomorphism, necrosis, endothelial proliferation and high MIB-1 labeling index (cell proliferation marker). These tumours are managed by surgery followed by Radiotherapy (RT), Chemotherapy (CT) and adjuvant CT Temozolomide (TMZ). To evaluate Epidermal Growth Factor Receptor (EGFR) protein expression in GBM patients. The study comprised of 52 cases of GBM diagnosed by histomorphology from biopsy specimens. Ancillary techniques like Immunohistochemistry (IHC) for Glial Fibrillary Acidic Protein (GFAP), cell proliferation marker (MIB-1 labeling index, P53 expressions) were done in all cases. EGFR protein expression was assessed by IHC as the percentage of positive tumour cells in hot spots (10 high power fields). Response to therapy was assessed at three months post therapy by using World Health Organization (WHO) Response Evaluation Criteria In Solid Tumours (RECIST) guideline. Statistical analysis was performed by using IBM-Statistical Package for Social Sciences (SPSS) software, version 20. The p-value of ≤ 0.05 was considered significant. The mean survival of the patients was calculated using unpaired t-test and ANOVA (analysis of variance) test. Out of 52 cases, thirty cases was EGFR positive and 22 cases were EGFR negative. Response to therapy was evident in 33 (63.5%) cases and 19 cases (36.5%) were non responders. The responders with EGFR negative were 86.4% and EGFR positive were 46.7% with a p-value of 0.003. The mean survival among EGFR positive and negative GBM were 315.73±257.54 and 657.91±305.88 days respectively with a significant p-value of 0.001. EGFR negative patients respond better to therapy along with longer duration of survival as compared to EGFR positive patient.

Progenitor Cell Dynamics in the Newt Telencephalon during Homeostasis and Neuronal Regeneration

SummaryThe adult newt brain has a marked neurogenic potential and is highly regenerative. Ventricular, radial glia-like ependymoglia cells give rise to neurons both during normal homeostasis and after injury, but subpopulations among ependymoglia cells have not been defined. We show here that a substantial portion of GFAP+ ependymoglia cells in the proliferative hot spots of the telencephalon has transit-amplifying characteristics. In contrast, proliferating ependymoglia cells, which are scattered along the ventricular wall, have stem cell features in terms of label retention and insensitivity to AraC treatment. Ablation of neurons remodels the proliferation dynamics and leads to de novo formation of regions displaying features of neurogenic niches, such as the appearance of cells with transit-amplifying features and proliferating neuroblasts. The results have implication both for our understanding of the evolutionary diversification of radial glia cells as well as the processes regulating neurogenesis and regeneration in the adult vertebrate brain.

Revisiting epidermal growth factor receptor in glioblastoma multiforme: does it play a role in response to therapy?

Glioblastoma multiforme (GBM) are the most aggressive class of cancer of central nervous system with hallmark characteristics that include rampant proliferation, necrosis, and endothelial proliferation. Epidermal growth factor receptor (EGFR) has been implicated as the primary contributor to glioblastoma initiation and succession. The present study was designed to evaluate EGFR protein expression in GBM as predictor of response to therapy and survival. Epidermal growth factor receptor was assessed by immunohistochemistry as a percentage of positive tumor cells in hot spots (10 high-power fields). The study group comprised of 35 cases of GBM. All cases underwent surgical resection and subsequently underwent radiotherapy (n = 17) or radiotherapy with adjuvant temozolomide chemotherapy (n = 18). Immediate response to therapy was assessed at 3 months using World Health Organization response evaluation criteria in solid tumors criteria and cases followed up for survival. Twenty-four cases (68.6%) expressed EGFR while 11/35 (31.4%) cases were negative. Response to therapy was evident in 21/35 cases (60.0%) and 14/35 were (40.0%) nonresponders. Mean EGFR protein expression in responders was 37.23 ± 33.70 and in nonresponders was 59.5 ± 39.46 (P = 0.542). The percentage of responders which were EGFR negative was 72.7% and while response in EGFR positive cases was observed in 54.2%. Mean survival in EGFR positive and negative GBM was 394.37 ± 189.11 and 420.54 ± 191.23 days, respectively. The EGFR negative cases appear to respond better to therapy, however, the difference is not statistically significant (P = 0.298). Further, EGFR protein expression does not play a definitive role in predicting survival. This is an original study evaluating EGFR in terms of therapeutic response.

Two-Staged Load Balancing Mechanism in LTE Self-Organization Networks

In mobile communication system, the traffic is time-varying and unpredictable, so there will be some hot-spot cells. It means that, the number of service request is much higher than an acceptable level in some cells, which may result in call-blocking with a large probability. But in other cells of system there are still resources available to serve more users. How to avoid the imbalance to effectively improve the system's resource utilization is what load balancing need to solve. In this paper, a new kind of event-trigger mechanism using cell load status information exchange between eNBs via X2 interface is presented. Additionally, based on it, a novel load balancing algorithm, named TSLB(two-staged load balancing), for LTE systems is put forward. Using this algorithm, eNBs can start corresponding load balancing procedure accurately according to the cell load status in real-time without any manual intervention. Simulation results show that the method is valid and it can increase the system throughput significantly as well as decrease the network delay.

Self-organising cluster-based cooperative load balancing in OFDMA cellular networks

Mobility load balancing MLB redistributes the traffic load across the networks to improve the spectrum utilisation. This paper proposes a self-organising cluster-based cooperative load balancing scheme to overcome the problems faced by MLB. The proposed scheme is composed of a cell clustering stage and a cooperative traffic shifting stage. In the cell clustering stage, a user-vote model is proposed to address the virtual partner problem. In the cooperative traffic shifting stage, both inter-cluster and intra-cluster cooperations are developed. A relative load response model is designed as the inter-cluster cooperation mechanism to mitigate the aggravating load problem. Within each cluster, a traffic offloading optimisation algorithm is designed to reduce the hot-spot cell's load and also to minimise its partners' average call blocking probability. Simulation results show that the user-vote-assisted clustering algorithm can select two suitable partners to effectively reduce call blocking probability and decrease the number of handover offset adjustments. The relative load response model can address public partner being heavily loaded through cooperation between clusters. The effectiveness of the traffic offloading optimisation algorithm is both mathematically proven and validated by simulation. Results show that the performance of the proposed cluster-based cooperative load balancing scheme outperforms the conventional MLB. Copyright © 2013 John Wiley & Sons, Ltd.