Intrinsic Feedback Research Articles

Primary T Cell Immunodeficiencies and Autoimmunity

Abstract SCI-21There are a variety of primary T cell immunodeficiencies that can impair T cell differentiation or T cell activation. The latter include CD38δ deficiency, ZAP70 deficiency, Ca++ influx deficiency (ORAI1 and Stim1 deficiencies), and ITK deficiency as well. A new T cell activation deficiency as observed in a patient with defective T cell receptor triggered T cell activation and low CD4 T cell counts will be reported. A remarkable and quasi constant feature shared by all those T cell activation defects is the occurrence of autoimmune diseases, mostly related to autoantibodies, and inflammation such as colitis or panniculitis. Several mechanisms can account for these findings that include defective regulatory T cell development or function, defective negative selection impaired intrinsic feedback mechanism as well as non TCR-mediated T cell activation ultimately leading to proinflammatory cytokines release and autoantibody production by B cells. Another new form of primary T cell immunodeficiency with autosomal recessive inheritance observed in four patients from two families will be described. It is characterized by defective survival of naïve T cells. There again, autoimmunity appeared to be a significant component of the phenotype. Collectively, these results indicate that further insight into the role of key molecules in T cell activation/survival is provided by the analysis of new primary immunodeficiency phenotypes. In addition, the occurrence of autoimmunity in these settings stresses on one hand the role of T cells in the control of reactivity to self and, on the other hand, should be considered in the therapeutic strategy of these conditions. Disclosures:No relevant conflicts of interest to declare.

Abstract B130: BRAFV600E negatively regulates the PI3K/AKT pathway in melanoma cell lines.

Abstract The BRAFV600E mutation is frequently found in human cancers (∼ 8%), with the highest incidence in melanoma (60–70%). Small molecules targeting BRAFV600E or MEK have shown significant clinical activity in melanoma patients carrying the BRAFV600E mutation. However, rapid acquisition of drug resistance is an emerging problem that limits patient survival benefits from these agents. MEK inhibition abrogates the intrinsic negative feedback on both RAS/RAF/MEK and PI3K/AKT pathways leading to induction of MEK and AKT phosphorylation. Induction of MEK and AKT phosphorylation may confer resistance and limit the clinical activity of MEK inhibitors. In this study, we investigated the molecular mechanisms of crosstalk between the two pathways. In NIH3T3 cells, engineered expression of BRAFV600E activates the MEK/ERK pathway leading to a significant growth advantage compared to control cells both in vitro and in vivo. MEK inhibition in NIH3T3 control cells strongly induces AKT phosphorylation (Thr308 and Ser473) and downstream signalling, whereas in NIH3T3 cells expressing BRAFV600E the AKT phosphorylation is significantly reduced. Knockdown of BRAFV600E restores MEK inhibition-induced elevation of AKT phosphorylation (pAKT). In the melanoma cell line with wild-type BRAF, MEK inhibition also induces pAKT (Thr308 and Ser473), whereas in the melanoma cell lines harbouring BRAFV600E, MEK inhibition-induced pAKT is not seen. Knockdown of BRAFV600E in those melanoma cell lines significantly elevates basal pAKT levels. These results suggest that BRAFV600E negatively regulates AKT pathway activation. In BRAFV600E melanoma cell lines, knockdown of MEK1/2 or ERK1/2 and inhibition of BRAF by RAF inhibitor have minimal effects on pAKT, suggesting that BRAFV600E suppresses AKT activation independent of the MEK/ERK downstream signals and its kinase activity. Furthermore, the elevation of pAKT(Thr308 and Ser473) caused by BRAFV600E knockdown can be abolished by Rictor, but not Raptor, knockdown, suggesting that the pAKT induction is Rictor dependent. Lack of pAKT induction in cells carrying BRAFV600E is associated with co-purification of Rictor-mTOR and Raptor-mTOR complexes, which is rarely seen in cells with wild type BRAF. Taken together, our data demonstrate that in BRAFV600E melanoma cells, BRAFV600E negatively regulates AKT phosphorylation in a Rictor-dependent, MEK/ERK and kinase-independent manner, possibly via altering Rictor-mTOR complex formation. This study reveals a novel molecular mechanism of crosstalk between the RAF/MEK and the PI3K/AKT pathways, suggesting an underlying mechanism whereby a subset of BRAFV600E melanoma cells are exquisitely sensitive to MEK inhibition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B130.

Design and Development of a Component-Based System for Virtual Patients in the Virtual World of Second Life®

This paper presents the development of a Component-Based System structured as a distributed three- tier architecture, enabling monitoring and information visualisation of application activity as well as presentation of feedback to learners via a Heads-Up-Display (HUD) in the virtual world of Second Life®. The activities follow a game- based learning approach and take place in a Respiratory Ward in Second Life®, where learners interact with virtual patients receiving intrinsic feedback about their diagnosis, investigations and treatments. The proposed architecture developed by the authors, consists of different virtual patient components that provide the relevant personal and clinical data to the clinical scenario; a data availability model that enables the sequencing and progressive disclosure of a virtual patient identifying triggers and scaffolding information, and an activity model which encodes the activities available and how the learner will be able to engage with the virtual patients.

IGF-1 induced HIF-1α-TLR9 cross talk regulates inflammatory responses in glioma

The insulin-like growth factor (IGF-1) induces hypoxia inducible factor (HIF-1α) regulated genes in glioblastoma multiforme (GBM). As HIF-1α links inflammatory and oncogenic pathways in GBM, we investigated whether IGF-1 affects HIF-1α to regulate inflammatory response in glioma cells under normoxia. IGF-1 induced Ras and Calmodulin-dependent kinase II (CaMKII) regulated HIF-1α transcriptional activity in glioma cells. Increase in HIF-1α was concurrent with decreased Toll-like receptor (TLR9) and CXCR4 expression and elevated suppressor of cytokine signaling (SOCS3) levels. Interestingly, while synthetic CpG containing oligodeoxynucleotide TLR9 agonist (CpG DNA) decreased IGF-1 mediated increase in HIF-1α activity, siRNA mediated knockdown of HIF-1α decreased TLR9 levels. This suggested that IGF-1 induced HIF-1α-TLR9 axis is regulated by both positive and negative feedback loops. Importantly, TLR9 agonist reversed the effect of IGF-1 on CXCR4 and SOCS3 expression. While knockdown of HIF-1α abrogated IGF-1 mediated increase in SOCS3 it elevated IGF-1 induced decrease in CXCR4 levels. Thus HIF-1α positively and negatively regulates SOCS3 and CXCR4 expression respectively, in glioma cells. Though TLR9 agonist had no additive effect on IGF-1 mediated increase in pro-inflammatory cytokines IL-1β, IL-6 and IL-8, treatment with TLR9 agonist alone elevated expression of these pro-inflammatory cytokines. Our studies indicate that a complex HIF-1α-TLR9 cross-talk sustains a self-regulating cycle of inflammatory response through intrinsic negative and positive feedback mechanisms.

P21WAF1 is component of a positive feedback loop that maintains the p53 transcriptional program

The regulation of p53 activity through the MDM2 negative feedback loop is driven in part by an extrinsic ATM-pulse that maintains p53 oscillations in response to DNA damage. We report here that the p53 pathway has evolved an intrinsic positive feedback loop that is maintained by the p53-inducible gene product p21WAF1. p21-null cancer cells have defects in p53 protein turnover, reductions in MDM2-mediated degradation of p53, and reduced DNA damage-induced ubiquitination of p53. TLR3-IRF1 or ATM-dependent signaling to p53 is defective in p21-null cells and complementation of the p21 gene in p21-null cancer cells restores the p53 transcriptional response. The mechanism of p53 inactivity in p21-null cells is linked to a p53 protein equilibrium shift from chromatin into cytosolic fractions and complementation of the p21 gene into p21-null cells restores the nuclear localization of p53. A loss of p53 transcriptional function in murine B-cells heterozygous or homozygous null for p21 highlights a p21-gene dosage effect that maintains the full p53 transcriptional response. ATM inhibition results in nuclear exclusion of p53 highlighting a positive genetic interaction between ATM and p21. P21 protein oscillates in undamaged proliferating cells, and reductions of p21 protein using siRNA eliminate the DNA damage-induced p53 pulse. The p53 transcription program has evolved a negative feedback loop maintained by MDM2 that is counteracted by a positive feedback loop maintained by ATM-p21 the balance of which controls the specific activity of p53 as a transcription factor.

INHERENT SAFETY ANALYSIS OF THE KALIMER UNDER A LOFA WITH A REDUCED PRIMARY PUMP HALVING TIME

The 600 MWe, pool-type, sodium-cooled, metallic fuel loaded KALIMER-600 (Korea Advanced LiquId MEtal Reactor, 600 MWe) has been conceptually designed with an emphasis on safety by self-regulating (inherent/intrinsic) negative reactivity feedback in the core. Its inherent safety under the ATWS (Anticipated Transient Without Scram) events was demonstrated in an earlier study. Initiating events of an HCDA (Hypothetical Core Disruptive Accident), however, also need to be analyzed for assessment of the margins in the current design. In this study, a hypothetical triple-fault accident, ULOF (Unprotected Loss Of Flow) with a reduced pump halving time, is investigated as an initiator of a core disruptive accident. A ULOF with insufficient primary pump inertia may cause core sodium boiling due to a power-to-flow mismatch. If the positive sodium reactivity resulting from this boiling is not compensated for by other intrinsic negative reactivity feedbacks, the resulting core power burst would challenge the fuel integrity. The present study focuses on determination of the limit of the pump inertia for assuring inherent reactivity feedback and behavior of the core after sodium boiling as well. Transient analyses are performed with the safety analysis code SSC-K, which now incorporates a new sodium boiling model. The results show that a halving time of more than 6.0 s does not allow sodium boiling even with very conservative assumptions. Boiling takes place for a halving time of 1.8 s, and its behavior can be predicted reasonably by the SSC-K.

RyR(R4496C) Mutant Mice Model Reveals a New Paradigm on Local Ca 2+ Control of I CaL

The Ca2+-dependent inactivation (CDI) of the widely distributed L-type Ca2+ channels is a major intrinsic feedback mechanism for Ca2+ homeostasis. CDI manifests by the time-dependent current decay during prolonged depolarization but also the voltage-dependent availability of Ca2+ channel during double-pulse protocols. Whereas the first one has received most of the attention cumulating with the identification of calmodulin (CaM) as an important Ca2+ sensor that mediates CDI, the latter has not received extensive investigation. Here we evidence that Ca2+ sparks control L-type Ca2+ current (ICaL) availability in cardiomyocytes and consequently the steady-state window current. Comparing RyRR4496C catecholaminergic polymorphic ventricular tachycardia (CPVT) mutant mice to wild type (WT) littermates, we show that whereas peak density of ICaL and global [Ca2+]i transient are not modified, RyR2R4496C myocytes demonstrated a significantly lower ICaL density at −30 and −20 mV. This decrease is the consequence of a depolarizing shift in steady-state activation and a hyperpolarizing shift of steady-state inactivation that result in a decreased window current. These differences are eliminated in presence of fast the Ca2+ buffer BAPTA and by depleting the sarcoplasmic reticulum (SR) with thapsigargin, pointing out to a local control by the observed increase in Ca2+ spark occurrence at low voltages in CPVT mice. Somewhat surprisingly, CaM antagonists did not have any effect on CPVT cells but altered the inactivation and activation curves in the WT cells to make these similar to the CPVT. Our data echo the retrograde coupling of RyR and L-type Ca2+ channel observed in skeletal muscle, representing a novel mechanism to counteract excessive SR Ca2+ leak and to preserve CPVT mice from arrhythmic trigger activity such as early afterdepolarization due to enhancement of ICaL window current.

‘Brute force’vs.‘gentle taps’ in the control of unstable loads

‘Brute force’<i>vs.</i>‘gentle taps’ in the control of unstable loads

Microwave noise modeling of FinFETs

The noise characteristics of advanced silicon semiconductor devices fabricated with FinFET technology are investigated and modeled at the probe tip reference planes in the microwave frequency range. The transistor noise model is obtained by assigning an equivalent temperature to each resistor of the small signal equivalent circuit. These temperatures are selected to be equal to the room temperature with the exception of the temperature values of the intrinsic output, feedback, and substrate resistances, which are selected in order to reproduce accurately the 50Ω noise factor measurements over a broadband frequency range going from 0.5GHz up to 26.5GHz. Accurate model simulations are obtained at such high frequencies, thanks to the inclusion of the noise temperature associated to the feedback and substrate resistances representing non-quasi-static effects which cannot be neglected in the investigated frequency range.

Influence of anatomic landmarks in the virtual environment on simulated angled laparoscope navigation

BackgroundThe aim of this study is to investigate the influence of the presence of anatomic landmarks on the performance of angled laparoscope navigation on the SimSurgery SEP simulator.MethodsTwenty-eight experienced laparoscopic surgeons (familiar with 30° angled laparoscope, >100 basic laparoscopic procedures, >5 advanced laparoscopic procedures) and 23 novices (no laparoscopy experience) performed the Camera Navigation task in an abstract virtual environment (CN-box) and in a virtual representation of the lower abdomen (CN-abdomen). They also rated the realism and added value of the virtual environments on seven-point scales.ResultsWithin both groups, the CN-box task was accomplished in less time and with shorter tip trajectory than the CN-abdomen task (Wilcoxon test, p < 0.05). No significant differences were found between the performances of the experienced participants and the novices on the CN tasks (Mann–Whitney U test, p > 0.05). In both groups, the CN tasks were perceived as hard work and more challenging than anticipated.ConclusionsPerformance of the angled laparoscope navigation task is influenced by the virtual environment surrounding the exercise. The task was performed better in an abstract environment than in a virtual environment with anatomic landmarks. More insight is required into the influence and function of different types of intrinsic and extrinsic feedback on the effectiveness of preclinical simulator training.

Intrinsic feedback and bistable switching in Y-branched nanojunctions

We present intrinsic feedback and nonlinear switching in Y-branched nanotransistors. For this type of mesoscopic transistor the gate efficiency depends on the density of states in the gate electrode which is altered by voltage shifts at the drain. This nonclassical property of a Y junction introduces positive voltage feedback which leads to pronounced nonlinearities and is exploited to demonstrate highly efficient gating and bistable switching. Our results demonstrate that the efficiency of nanoscaled transistors can be enhanced dramatically by exploiting quantum effects.

A 58–65 GHz Neutralized CMOS Power Amplifier With PAE Above 10% at 1-V Supply

A 60-GHz band, three-stage pseudo-differential power amplifier (PA) is implemented with input and output baluns on-chip. Each stage consists of a neutralized common-source amplifier pair. Neutralization mitigates the intrinsic gate-drain feedback of each transistor for increased power gain and reverse isolation. Shielded transformers couple the gain stages and allow low supply voltage operation. Fabricated in a 65-nm bulk CMOS process, the measured small-signal gain of the 0.13 × 0.41 mm2 PA is 16 dB at 60 GHz with 3-dB bandwidth more than 8.5 GHz, while consuming 50 mW from a 1-V supply. Reverse isolation is better than 42 dB from 55 to 65 GHz. Maximum saturated output power is 11.5 dBm with a peak PAE of 15.2% measured at 62 GHz; from 58 to 65 GHz, the measured PAE is above 10%.

Deriving a power amplifier linearizer from a physics-based system-level model

The RF power amplifier (PA) is a nonlinear system with an intrinsic and dynamic feedback mechanism. The application of an adequate linearizer (which is also a nonlinear dynamic system) inserted at the input of the signal path (i.e., predistortion) is very important to maintain a linear transmission chain when the PA carries high power signals (avoiding spectral regrowth). This article presents a new PA linearizer model whose topology has support on the physical behavior of the general PA electronic circuit. As the proposed model is of a feed-forward nature, it is suited for implementation on digital hardware devices, such as field programmable gate array and digital signal processor. Validation tests were performed on the linearization of a 900 MHz PA excited with WCDMA-3GPP signals. Comparison with other state-of-the-art linearizer models is included, demonstrating very good linearization results. Moreover, this model has potential to be an adequate linearizer for a wider range of applications since it has physical support. © 2010 Wiley Periodicals, Inc. Int J RF and Microwave CAE, 2010.

Modeling, Analysis, and Optimal Design of the Automotive Transmission Ball Capsule System

Clutch shift control is critical for the performance and fuel economy of automotive transmissions, including both automatic and hybrid transmissions. Among all the factors that influence clutch shift control, clutch fill and clutch engagement are crucial to realize a fast and smooth clutch shift. When the clutch is not engaged, the fluid held by the centrifugal force inside of the clutch chamber, which introduces additional pressure that will affect the subsequent clutch fill and engagement processes, should be released. To realize this function, a ball capsule system is introduced and mounted on the clutch chamber. When the clutch chamber is ready to be filled for engagement, the ball capsule needs to close quickly and remain closed until the clutch is disengaged. It is also desirable to have an appropriate closing velocity for the ball capsule to minimize noise and wear. In this paper, the ball capsule dynamics is modeled, in which the derivation of the ball capsule throttling area is considered novel and critical because of its asymmetrical nature. Through this, the ball capsule’s intrinsic positive feedback structure is also revealed, which is considered to be the key to realize a fast response. Moreover, through the system dynamics analysis, the slope angle of the capsule is found to be an effective control parameter for system performance and robustness. To this end, the optimal shape of the capsule is designed using dynamic programming to achieve the desired performance.

MAGUK-Controlled Ubiquitination of CARMA1 Modulates Lymphocyte NF-κB Activity

The adaptor protein CARMA1 is required for antigen receptor-triggered activation of IKK and JNK in lymphocytes. Once activated, the events that subsequently turn off the CARMA1 signalosome are unknown. In this study, we found that antigen receptor-activated CARMA1 underwent lysine 48 (K48) polyubiquitination and proteasome-dependent degradation. The MAGUK region of CARMA1 was an essential player in this event; the SH3 and GUK domains contained the main ubiquitin acceptor sites, and deletion of a Hook domain (an important structure for maintaining inactive MAGUK proteins) between SH3 and GUK was sufficient to induce constitutive ubiquitination of CARMA1. A similar deletion promoted the ubiquitination of PSD-95 and Dlgh1, suggesting that a conserved mechanism may control the turnover of other MAGUK family protein complexes. Functionally, we demonstrated that elimination of MAGUK ubiquitination sites in CARMA1 resulted in elevated basal and inducible NF-kappaB and JNK activation as a result of defective K48 ubiquitination and increased persistence of this ubiquitination-deficient CARMA1 protein in activated lymphocytes. The coordination of degradation with the full activation of the CARMA1 molecule likely provides an intrinsic feedback control mechanism to balance lymphocyte activation upon antigenic stimulation.

Self-organization of intracellular gradients during mitosis

Gradients are used in a number of biological systems to transmit spatial information over a range of distances. The best studied are morphogen gradients where information is transmitted over many cell lengths. Smaller mitotic gradients reflect the need to organize several distinct events along the length of the mitotic spindle. The intracellular gradients that characterize mitosis are emerging as important regulatory paradigms. Intracellular gradients utilize intrinsic auto-regulatory feedback loops and diffusion to establish stable regions of activity within the mitotic cytosol. We review three recently described intracellular mitotic gradients. The Ran GTP gradient with its elaborate cascade of nuclear transport receptors and cargoes is the best characterized, yet the dynamics underlying the robust gradient of Ran-GTP have received little attention. Gradients of phosphorylation have been observed on Aurora B kinase substrates both before and after anaphase onset. In both instances the phosphorylation gradient appears to result from a soluble gradient of Aurora B kinase activity. Regulatory properties that support gradient formation are highlighted. Intracellular activity gradients that regulate localized mitotic events bare several hallmarks of self-organizing biologic systems that designate spatial information during pattern formation. Intracellular pattern formation represents a new paradigm in mitotic regulation.

Why and how physical activity promotes experience-induced brain plasticity.

Adult hippocampal neurogenesis is an unusual case of brain plasticity, since new neurons (and not just neurites and synapses) are added to the network in an activity-dependent way. At the behavioral level the plasticity-inducing stimuli include both physical and cognitive activity. In reductionistic animal studies these types of activity can be studied separately in paradigms like voluntary wheel running and environmental enrichment. In both of these, adult neurogenesis is increased but the net effect is primarily due to different mechanisms at the cellular level. Locomotion appears to stimulate the precursor cells, from which adult neurogenesis originates, to increased proliferation and maintenance over time, whereas environmental enrichment, as well as learning, predominantly promotes survival of immature neurons, that is the progeny of the proliferating precursor cells. Surprisingly, these effects are additive: boosting the potential for adult neurogenesis by physical activity increases the recruitment of cells following cognitive stimulation in an enriched environment. Why is that? We argue that locomotion actually serves as an intrinsic feedback mechanism, signaling to the brain, including its neural precursor cells, increasing the likelihood of cognitive challenges. In the wild (other than in front of a TV), no separation of physical and cognitive activity occurs. Physical activity might thus be much more than a generally healthy garnish to leading “an active life” but an evolutionarily fundamental aspect of “activity,” which is needed to provide the brain and its systems of plastic adaptation with the appropriate regulatory input and feedback.

Pharmacologic Administration of Interleukin‐2

The development of biologic therapies for patients with cancer has in part been impeded by the extraordinary complexity and intrinsic feedback mechanisms promoting homeostasis in tissue injury, repair, inflammation, and immunity. Recombinant interleukin 2 (IL-2) therapy was initiated in 1984 based on its role as the prototypic T-cell growth factor, with novel roles deduced late after its FDA approval in regulating not only effector T cells but also regulatory T cells. Complicating its application, even in the most sophisticated centers, has been the manageable but difficult toxicities attendant on its use in spite of clear evidence of complete responses in 5-10% of treated patients with melanoma and renal cell carcinoma with extraordinary durability lasting now for almost 25 years, thus tantamount to "cures." Although efforts have been made to diminish toxicity or enhance efficacy the only substantive advance in combination therapy has been the application of tumor-infiltrating lymphocytes and the antibody to CTLA4. A deeper understanding of the "limiting" toxicity associated with mild flu-like symptoms and more debilitating cytokine "storm" not forthcoming. Here we propose the notion that the systemic syndrome associated with IL-2 administration is due to global cytokine-induced autophagy and temporally limited tissue dysfunction. The possible role of autophagy inhibitors to enhance efficacy and limit toxicity as well as possible problems with this approach are considered.

Intrinsic activity and positive feedback in motor circuits in organotypic spinal cord slice cultures

In co-cultures of embryonic rat spinal cord slices and skeletal muscle, spinal motoneurons innervate muscle fibres and drive muscle contractions. However, multi-electrode array (MEA) recordings show that muscle contractions often appear in the absence of population activity in the spinal cord networks. Such uncorrelated muscle activity persists when the population bursts in the neuronal networks are prevented by un-coupling the network with the glutamatergic antagonists CNQX and D-APV. By contrast, the uncorrelated muscle activity is fully suppressed by the muscular nicotinic antagonist D-tubocurarine. Together, these findings confirm the previous finding that motoneurons drive muscle fibres in this preparation and suggest that they are intrinsically spiking in the absence of synaptic input. Intracellular recordings from spinal neurons support this suggestion. Analysing the correlated muscle activity, we found that in 15% of the population bursts, muscle activity appears at the beginning or before neuronal activity, suggesting that in these cases motoneurons initiate the population activity. Both the total number of population bursts and the percentage of such bursts that are initiated by muscle activity are reduced by a block of nicotinic receptors. Uncorrelated muscle and neuronal activity is reduced by the gap junction blocker carbenoxolone, suggesting that electrical coupling is involved in the generation of this activity. Together, these findings suggest that intrinsic firing of motoneurons may contribute to the activation of population bursts through cholinergic positive feedback loops in cultured spinal networks.

Novel block decision feedback equalizers for MIMO-OFDM used in UTRA LTE for UTRA LTE

The long term evolution of UMTS Terrestrial Radio Access, abbreviated as UTRA LTE, will use OFDM (orthogonal frequency division multiplexing) combined with MIMO (multiple-input multiple-output), termed MIMO-OFDM. And spatial multiplexing MIMO scheme is deployed in UTRA LTE downlink to provide high data rates. Considering the detection of spatial multiplexing signals, well-known techniques such as the V-BLAST schemes provide an attractive error ratio performance, but still a considerable signal processing effort, which merits further research towards less complex schemes. In this communication, the authors will propose a novel set of detection techniques which use intrinsic block decision feedback equalization (BDFE) characteristics instead of successive interference cancellation (SIC). Both zero-forcing (ZF) and minimum mean square error (MMSE) schemes based BDFE are proposed, termed as MIMO-BDFE-ZF and MIMO-BDFE-MMSE. Setting out from a novel general model for the evaluation of the signal-to-noise ratio (SNR) at the data detector output, the authors will evaluate the error ratio performance of the novel MIMO-BDFE and provide comparison results. It will be shown that the porposed scheme provide an attractive performance at a lower realization complexity.