Unbalanced Response Research Articles

Decoy Receptor 3 Improves Survival in Experimental Sepsis by Suppressing the Inflammatory Response and Lymphocyte Apoptosis.

PurposeUnbalanced inflammatory response and lymphocyte apoptosis is associated with high mortality in septic patients. Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an anti-inflammatory and anti-apoptotic factor. Recently, DcR3 expression was found to be increased in septic patients. This study evaluated the therapeutic effect and mechanisms of DcR3 on cecal ligation and puncture (CLP)-induced sepsis in mice.MethodsC57BL/6 mice were subjected to CLP-induced polymicrobial sepsis. DcR3 Fc was intravenously injected 30 min before and 6 h after CLP. Bacterial clearance, cytokine production, histology, lymphocyte apoptosis and survival were evaluated. Furthermore, we investigated the systemic effects of DcR3 in in vitro lymphocyte apoptosis regulation.ResultsOur results demonstrated that DcR3 protein treatments significantly improved survival in septic mice (p <0.05). Treatment with DcR3 protein significantly reduced the inflammatory response and decreased lymphocyte apoptosis in the thymus and spleen. Histopathological findings of the lung and liver showed milder impairment after DcR3 administration. In vitro experiments showed that DcR3 Fc inhibited Fas-FasL mediated lymphocyte apoptosis.ConclusionsTreatment with the DcR3 protein protects mice from sepsis by suppressing the inflammatory response and lymphocyte apoptosis. DcR3 protein may be useful in treatment of sepsis.

Host proteome correlates of vaccine-mediated enhanced disease in a mouse model of respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants. Despite over 50 years of research, to date no safe and efficacious RSV vaccine has been licensed. Many experimental vaccination strategies failed to induce balanced T-helper (Th) responses and were associated with adverse effects such as hypersensitivity and immunopathology upon challenge. In this study, we explored the well-established recombinant vaccinia virus (rVV) RSV-F/RSV-G vaccination-challenge mouse model to study phenotypically distinct vaccine-mediated host immune responses at the proteome level. In this model, rVV-G priming and not rVV-F priming results in the induction of Th2 skewed host responses upon RSV challenge. Mass spectrometry-based spectral count comparisons enabled us to identify seven host proteins for which expression in lung tissue is associated with an aberrant Th2 skewed response characterized by the influx of eosinophils and neutrophils. These proteins are involved in processes related to the direct influx of eosinophils (eosinophil peroxidase [Epx]) and to chemotaxis and extravasation processes (Chil3 [chitinase-like-protein 3]) as well as to eosinophil and neutrophil homing signals to the lung (Itgam). In addition, the increased levels of Arg1 and Chil3 proteins point to a functional and regulatory role for alternatively activated macrophages and type 2 innate lymphoid cells in Th2 cytokine-driven RSV vaccine-mediated enhanced disease. RSV alone is responsible for 80% of acute bronchiolitis cases in infants worldwide and causes substantial mortality in developing countries. Clinical trials performed with formalin-inactivated RSV vaccine preparations in the 1960s failed to induce protection upon natural RSV infection and even predisposed patients for enhanced disease. Despite the clinical need, to date no safe and efficacious RSV vaccine has been licensed. Since RSV vaccines have a tendency to prime for unbalanced responses associated with an exuberant influx of inflammatory cells and enhanced disease, detailed characterization of primed host responses has become a crucial element in RSV vaccine research. We investigated the lung proteome of mice challenged with RSV upon priming with vaccine preparations known to induce phenotypically distinct host responses. Seven host proteins whose expression levels are associated with vaccine-mediated enhanced disease have been identified. The identified protein biomarkers support the development as well as detailed evaluation of next-generation RSV vaccines.

Abstract T MP70: Genetic Deletion of the Prostaglandin E2 EP3 Receptor Improves Outcomes after Experimental Intracerebral Hemorrhage in Young and Old Mice

Intracerebral hemorrhage (ICH) is a type of hemorrhagic stroke associated with high mortality and morbidity rates. Prolonged and unbalanced inflammatory responses after hemorrhagic stroke may negatively contribute to secondary brain injury. Prostaglandin E2 (PGE 2 ) is an important mediator of inflammation and plays a role in several neurologic disorders. PGE 2 has selective high affinity toward its membrane-bound G-protein-coupled receptors EP1, EP2, EP3, and EP4, which together arbitrate its neuromodulatory effects. We have previously shown in a middle cerebral artery occlusion model of ischemia/reperfusion-induced brain injury and a striatal NMDA-induced excitotoxicity model that mice pretreated intracerebroventricularly with a selective EP3 receptor agonist have larger brain lesions when compared to control mice. In the present study, we investigated whether EP3 receptor deletion (EP3 -/- ) would lead to improved anatomical and functional outcomes in young (2-4mo) and aged (22-24mo) C57BL/6 mice after inducing a hemorrhagic stroke using the collagenase model of ICH (n=8-10 for all groups). Neurobehavioral testing, including video-recording of home cage activity and neurological deficit scoring was performed at 24h, 48h, and 72h post-ICH. At 72h, mice were transcardially perfused and brains isolated for Cresyl Violet staining and lesion volume quantification. In both young and aged mice, smaller brain lesion volumes were seen for the EP3 -/- when compared to age-matched wildtype controls (p&lt;0.05). Further, the aged EP3 -/- displayed significantly better neurologic recovery at 72h, as identified by both behavioral tests (p&lt;0.01). Interestingly, the aged EP3 -/- showed significantly reduced ambulatory and stereotypic activity at 24h post-ictus (p&lt;0.005). No significant behavioral differences were seen in the young cohort. Collectively, these results indicate a dynamic role of the EP3 receptor in mediating anatomical and functional outcomes following ICH. Additional studies are needed in order to clarify the mechanisms involved and identify potential therapeutic paradigms for alleviating the initial PGE 2 -EP3 receptor associated toxicity and promoting its later beneficial effects.

The Effects of Paracoccidioides brasiliensis Infection on GM-CSF- and M-CSF-Induced Mouse Bone Marrow-Derived Macrophage from Resistant and Susceptible Mice Strains.

Considering the importance of macrophages as the first line of defense against fungal infection and the different roles played by the two M1- and M2-like polarized macrophages, we decided to evaluate the effects of Paracoccidioides brasiliensis infection on GM-CSF- and M-CSF-induced bone marrow-derived macrophages (BMM) from the A/J and B10.A mouse strains, an established model of resistance/susceptibility to PCM, respectively. Upon differentiation, the generated GM- or M-BMMs were characterized by morphological analyses, gene expression profiles, and cytokines production. Our main results demonstrate that GM-BMMs derived from A/J and B.10 produced high levels of pro- and anti-inflammatory cytokines that may contribute to generate an unbalanced early immune response. In accordance with the literature, the B10.A susceptible mice lineage has an innate tendency to polarize into M1-like phenotype, whereas the opposite phenotype occurs in A/J resistance mice. In this context, our data support that susceptibility and resistance are strongly correlated with M1 and M2 polarization, respectively.

PID Controller Design for UPS Three-Phase Inverters Considering Magnetic Coupling

In three-phase inverters used in uninterruptible power supplies (UPSs), three-limb inductors and three-limb transformers are commonly used in consideration of cost and size. However, magnetic coupling exists between the three phases of the inverter, which can result in complex models. When instantaneous feedback control strategies are introduced to achieve high quality output waveforms, the transient analysis of the closed-loop inverters becomes difficult. In this paper, the phenomenon of magnetic coupling in three-phase inverters due to three-limb inductors and three-limb transformers is analyzed. A decoupled dynamic model is derived based on the instantaneous symmetrical components transformation, which comprises three decoupled equivalent circuits of instantaneous symmetrical components. Analyses based on this model indicate that magnetic coupling may have a significant impact on the performance of three-phase inverters under unbalanced load conditions and transient responses. For three-phase inverters in UPSs with Proportional-Integral-Differential (PID) closed-loop control strategies, the interactive influence between instantaneous closed-loop regulation and magnetic coupling is researched. Finally, a method of reliability analysis and PID controller design for inverters with magnetic coupling is derived. Simulation and experiment results validate the model and conclusions.

Music and hearing aids.

The signal processing and fitting methods used for hearing aids have mainly been designed to optimize the intelligibility of speech. Little attention has been paid to the effectiveness of hearing aids for listening to music. Perhaps as a consequence, many hearing-aid users complain that they are not satisfied with their hearing aids when listening to music. This issue inspired the Internet-based survey presented here. The survey was designed to identify the nature and prevalence of problems associated with listening to live and reproduced music with hearing aids. Responses from 523 hearing-aid users to 21 multiple-choice questions are presented and analyzed, and the relationships between responses to questions regarding music and questions concerned with information about the respondents, their hearing aids, and their hearing loss are described. Large proportions of the respondents reported that they found their hearing aids to be helpful for listening to both live and reproduced music, although less so for the former. The survey also identified problems such as distortion, acoustic feedback, insufficient or excessive gain, unbalanced frequency response, and reduced tone quality. The results indicate that the enjoyment of listening to music with hearing aids could be improved by an increase of the input and output dynamic range, extension of the low-frequency response, and improvement of feedback cancellation and automatic gain control systems.

Unbalanced Adaptive and Innate Immune Responses during TB-IRIS

Unbalanced Adaptive and Innate Immune Responses during TB-IRIS

Modal Analysis and Unbalanced Response Analysis of Rotor System

In this article, the entity model of the bearing-rotor system is established and meshed in ANSYS. The natural frequency and vibration mode of the rotor system is analyzed in order to avoid the occurrence of resonance. At the same time, the results showed that not only the location of the unbalance incentive of the system should be taken into account, but also consider the size of the unbalanced force.

Sideband characterization and atmospheric observations with various 340 GHz heterodyne receivers

This paper describes sideband response measurements and atmospheric observations with a double sideband and two Single Sideband (SSB) receiver prototypes developed for the multi-beam limb sounder instrument stratosphere-troposphere exchange and climate monitor radiometer. We first show an advanced Fourier-Transform Spectroscopy (FTS) method for sideband response and spurious signal characterization. We then present sideband response measurements of the different prototype receivers and we compare the results of the SSB receivers with sideband measurements by injecting a continuous wave signal into the upper and lower sidebands. The receivers were integrated into a total-power radiometer and atmospheric observations were carried out. The observed spectra were compared to forward model spectra to conclude on the sideband characteristics of the different receivers. The two sideband characterization methods show a high degree of agreement for both SSB receivers with various local oscillator settings. The measured sideband response was used to correct the forward model simulations. This improves the agreement with the atmospheric observations and explains spectral features caused by an unbalanced sideband response. The FTS method also allows to quantify the influence of spurious harmonic responses of the receiver.

Recombinant measles viruses expressing respiratory syncytial virus proteins induced virus-specific CTL responses in cotton rats

Respiratory syncytial virus (RSV) is a common cause of serious lower respiratory tract illnesses in infants. Natural infections with RSV provide limited protection against reinfection because of inefficient immunological responses that do not induce long-term memory. RSV natural infection has been shown to induce unbalanced immune response. The effective clearance of RSV is known to require the induction of a balanced Th1/Th2 immune response, which involves the induction of cytotoxic T lymphocytes (CTL). In our previous study, recombinant AIK-C measles vaccine strains MVAIK/RSV/F and MVAIK/RSV/G were developed, which expressed the RSV fusion (F) protein or glycoprotein (G). These recombinant viruses elicited antibody responses against RSV in cotton rats, and no infectious virus was recovered, but small amounts of infiltration of inflammatory cells were observed in the lungs following RSV challenge. In the present study, recombinant AIK-C measles vaccine strains MVAIK/RSV/M2-1 and MVAIK/RSV/NP were developed, expressing RSV M2-1 or Nucleoprotein (NP), respectively. These viruses exhibited temperature-sensitivity (ts), which was derived from AIK-C, and expressed respective RSV antigens. The intramuscular inoculation of cotton rats with the recombinant measles virus led to the induction of CD8+ IFN-γ+ cells. No infectious virus was recovered from a lung homogenate following the challenge. A Histological examination of the lungs revealed a significant reduction in inflammatory reactions without alveolar damage. These results support the recombinant measles viruses being effective vaccine candidates against RSV that induce RSV-specific CTL responses with or without the development of an antibody response.

Dynamic design methodology of high speed micro-spindles for micro/meso-scale machine tools

With the increasing demands for high manufacturing accuracy and processing efficiency, micro/meso-scale machine tool systems are proposed. The availability of micro-spindles with ultra-high rotating angular speeds and ultra-small run-out are a key technology for micro/meso-scale cutting processes. Well-established design methods exist for traditional spindle systems, but there is a strong demand for a methodology to predict the dynamic characteristics, particularly at the micro-scale, which will dictate manufacturing accuracy. In this respect, the minimization of run-out is of paramount importance. In response to this, two problem areas are considered in this paper: (a) hybrid air bearing systems—a methodology related to the calculation of the load capacity and stiffness of hybrid air journal and thrust bearings, and (b) spindle rotor system—a methodology for the rotor dynamic analysis including critical speed, mode shape, and unbalanced response predictions. Mathematical models and simulation procedures are given, followed by explanations of their use. Finally, the proposed dynamic design method is demonstrated on a realized micro-spindle system model. Two designs namely the original design and a modified design are analyzed and comparisons are carried out. The numerical simulations and the experimental evidence available for the original design have substantiated the validity of the proposed dynamic design method. The proposed methodology lays the foundation for controlling run-out of the high speed micro-spindles in micro/meso-scale machine tools.

Inflammasomes in Respiratory Disease: From Bench to Bedside

The respiratory tract of human subjects is constantly exposed to harmful microbes and air pollutants. The immune system responds to these offenders to protect the host, but an unbalanced inflammatory response itself may promote tissue damage and ultimately lead to acute and chronic respiratory diseases. Deregulated inflammasome activation is emerging as a key modulator of respiratory infections and pathologic airway inflammation in patients with asthma, COPD, and pulmonary fibrosis. Assembly of these intracellular danger sensors in cells of the respiratory mucosa and alveolar compartment triggers a proinflammatory cell death mode termed pyroptosis and leads to secretion of bioactive IL-1β and IL-18. Here, we summarize and review the inflammasome and its downstream effectors as therapeutic targets for the treatment of respiratory diseases.

Krylov subspace-based model order reduction for Campbell diagram analysis of large-scale rotordynamic systems

This paper focuses on a model order reduction (MOR) for large-scale rotordynamic systems by using finite element discretization. Typical rotor-bearing systems consist of a rotor, built-on parts, and a support system. These systems require careful consideration in their dynamic analysis modeling because they include unsymmetrical stiffness, localized nonproportional damping, and frequency-dependent gyroscopic effects. Because of this complex geometry, the finite element model under consideration may have a very large number of degrees of freedom. Thus, the repeated dynamic analyses used to investigate the critical speeds, stability, and unbalanced response are computationally very expensive to complete within a practical design cycle. In this study, we demonstrate that a Krylov subspace-based MOR via moment matching significantly speeds up the rotordynamic analyses needed to check the whirling frequencies and critical speeds of large rotor systems. This approach is very efficient, because it is possible to repeat the dynamic simulation with the help of a reduced system by changing the operating rotational speed, which can be preserved as a parameter in the process of model reduction. Two examples of rotordynamic systems show that the suggested MOR provides a significant reduction in computational cost for a Campbell diagram analysis, while maintaining accuracy comparable to that of the original systems.

Bifurcation and chaos analysis of nonlinear rotor system with axial-grooved gas-lubricated journal bearing support

Axial-grooved gas-lubricated journal bearings have been widely applied to precision instrument due to their high accuracy, low friction, low noise and high stability. The rotor system with axial-grooved gas-lubricated journal bearing support is a typical nonlinear dynamic system. The nonlinear analysis measures have to be adopted to analyze the behaviors of the axial-grooved gas-lubricated journal bearing-rotor nonlinear system as the linear analysis measures fail. The bifurcation and chaos of nonlinear rotor system with three axial-grooved gas-lubricated journal bearing support are investigated by nonlinear dynamics theory. A time-dependent mathematical model is established to describe the pressure distribution in the axial-grooved compressible gas-lubricated journal bearing. The time-dependent compressible gas-lubricated Reynolds equation is solved by the differential transformation method. The gyroscopic effect of the rotor supported by gas-lubricated journal bearing with three axial grooves is taken into consideration in the model of the system, and the dynamic equation of motion is calculated by the modified Wilson-θ-based method. To analyze the unbalanced responses of the rotor system supported by finite length gas-lubricated journal bearings, such as bifurcation and chaos, the bifurcation diagram, the orbit diagram, the Poincare map, the time series and the frequency spectrum are employed. The numerical results reveal that the nonlinear gas film forces have a significant influence on the stability of rotor system and there are the rich nonlinear phenomena, such as the periodic, period-doubling, quasi-periodic, period-4 and chaotic motion, and so on. The proposed models and numerical results can provide a theoretical direction to the design of axial-grooved gas-lubricated journal bearing-rotor system.

Nonparametric Stochastic Modeling of Structural Uncertainty in Rotordynamics: Unbalance and Balancing Aspects

This paper focuses on extending an earlier investigation on the systematic and rational consideration of uncertainty in reduced order models of rotordynamics systems. The current effort concentrates on the consistent introduction of uncertainty in mass properties on the modal mass and gyroscopic matrices and on the unbalance force vector. The uncertainty in mass is separated into uncertainty that maintains the rotor symmetry and the one which disrupts it. Both types of uncertainties lead to variations in the system modal matrices but only the latter induces an unbalance. Accordingly, the approach permits the selection of separate levels on the uncertainty on the system properties (e.g., natural frequencies) and on the unbalance. It was first found that the unbalanced response is increased by considering the uncertainty in the rotor modal mass matrices. It was next noted that the approach presented not only permits the analysis of uncertain rotors but it also provides a computational framework for the assessment of various balancing strategies. To demonstrate this unique feature, a numerical experiment was conducted in which a population of rotors were balanced at low speed and their responses were predicted at their first critical speed. These response predictions were carried with the uncertainty in the system modal mass matrices but with or without the balancing weights effects on these matrices. It was found that the balancing at low speed may, in fact, lead to an increase in both the mean and 95th percentile of the response at critical speed.

Inflammation and Infection in Critical Care Medicine

Inflammation and infection are closely linked in critically ill patients. When adaptive immunity fails to prevent or control infection, an exacerbated/maintained inflammatory response emerges as consequence. It could be considered as an attempt of the immune system to fight the infection, which, in so many occasions, results insufficiently. In turn, uncontrolled inflammatory responses impair the development of specific and targeted responses against the infecting microbe, closing a vicious circle. The consequences of unbalanced inflammatory and adaptive responses to infection are microbial escape and tissue damage, contributing to the physiopathogenesis of sepsis, acute respiratory distress syndrome, or multiorganic failure. In this special issue, Steel C. et al. review the major virulence factors of S. pneumoniae and their role in triggering overexuberant inflammatory responses contributing to the immunopathogenesis of invasive disease in community-acquired pneumonia (CAP). These authors provided an insight into the pharmacological, anti-inflammatory strategies with adjunctive potential in the antimicrobial chemotherapy of CAP. In turn, Surbatovic M. et al. explored some of the more novel elements of immunoinflammatory response in severe sepsis and severe trauma, highlighting the role of Toll-like receptors, cytokines, and the genetic polymorphisms in the immune response to infection. Esteban E. et al. summarized the immune modulation actions of extracorporeal devices in the context of endotoxin removal, elimination of cytokines and inflammatory molecules, vascular and coagulation proteins, and removal of cells, which might play a role as an innovative coadjuvant treatment in sepsis or nonseptic respiratory failure. De Pascale G. et al. reviewed the role of mannose-binding lectin (MBL) in severe sepsis and septic shock. MBLs are serum proteins that recognize a wide range of pathogenic microorganisms and activate complement cascade via the antibody-independent pathway. While MBL-deficient patients are at increased risk of infection acquisition, an excess of MBL activation may drive unbalanced proinflammatory responses and additional host injury. MBL replacement therapy was also discussed. An original article from Rodriguez-Fernandez A. and colleagues revealed the protective role of eosinophils in S. aureus ventilator-associated pneumonia. Being a recognised actor in the pathophysiology of asthma, there is an increasing body of evidence on the antimicrobial roles played by eosinophils. This paper highlights the potential of an unexpensive tool such as the leukogram as biomarker in severe infections. Finally, Koch A. et al. investigated the regulation and prognostic relevance of symmetric dimethylarginine (SDMA) serum concentrations in critical illness and sepsis. SDMA impacts vascular tension and integrity via modulating nitric oxide (NO) pathways. These authors identified SDMA serum concentrations at admission as an independent prognostic biomarker in critically ill patients not only for short-term mortality at the ICU but also for unfavourable long-term survival, with patients with sepsis showing the highest SDMA levels. They proposed this molecule as a novel biomarker for mortality risk stratification for ICU patients. We hope that this compilation will be of interest for both clinicians and researchers working in the field of host immune responses to infection in severely ill patients. Jesus F. Bermejo-Martin Ignacio Martin-Loeches Steven Bosinger

Design of magnetic bearings for turbo refrigerant compressors

Magnetic bearings are oil-free bearings that are widely employed in turbo machineries such as turbo refrigerant compressors in order to eliminate lubrication systems, avoid contamination, and increase efficiency. We have developed a 145 refrigerant ton (RT)-class turbo refrigerant compressor using homopolar-type radial hybrid magnetic bearings (HMBs) and thrust magnetic bearings. The thrust magnetic bearing comprises a thrust HMB and a permanent magnet that generate downward forces to overcome high upward thrust forces of 2000 N at 21 000 rpm. A test rig and controller for the compressor with magnetic bearings were fabricated, and rotordynamics such as the unbalance response and axial displacement were investigated. Rotordynamics analyses using the finite element method predicted that the 1st bending mode is located at a high frequency with sufficient margin from the operating speeds. Further, the zero-to-peak displacement caused by the unbalanced response was sufficiently small. The rotor was stably supported with few vibrations across the entire range of the operational speeds. Our results demonstrate that the advantages of oil-free bearings can be easily exploited in turbo machineries such as turbo refrigerant compressors by adopting HMBs.

More Happy or Less Unhappy? Comparison of the Balanced and Unbalanced Designs for the Response Scale of General Happiness

The single-item measure of general happiness has been widely used in questionnaires due to the advantages of easy implementation in surveys for comparison across time and culture. The balanced response scale that includes equal positive and negative response categories based on Likert-type response format has been commonly applied. However, the possibility of using an unbalanced response scale for happiness, for instance, more choices on the happy side, has not been fully examined. This study aims to explore the optimal number of response categories and the corresponding labels for general happiness by using telephone survey data in Taiwan. Six types of response scales with different combinations of response number and response labels were examined to distinguish both the intensity and direction of responses. A completely randomized experimental design using computer-assisted telephone interviewing system was conducted to collect data from representative samples aged 18 years or older. Individual characteristics among the six groups indicated that all of the sub-samples were similar in terms of gender, age, education, marital status, working status, and monthly income. Results of the graded response model suggested that a scale with at least three response categories on the positive side and no more than two on the negative side will be suitable for the single measure of general happiness. Findings of ordered logit regression on happiness were also in favor of an unbalanced response design. A discussion of the result is provided.

Analysis of Gear Static Transmission Error and Mesh Stiffness

In this paper, the object of study is one pair increasing gear with building a two-dimensional plane model in ANSYS. According to the gears meshing theory, considering the gear deformation, solve the static transmission error and the gear mesh stiffness in different conditions. The influence of the centre errors on static transmission error and mesh Stiffness are basis for modal analysis based on the mesh stiffness of gear and unbalanced harmonic response.

Transformation of Receptive Field Properties from Lateral Geniculate Nucleus to Superficial V1 in the Tree Shrew

Tree shrew primary visual cortex (V1) exhibits a pronounced laminar segregation of inputs from different classes of relay neurons in the lateral geniculate nucleus (LGN). We examined how several receptive field (RF) properties were transformed from LGN to V1 layer 4 to V1 layer 2/3. The progression of RF properties across these stages differed markedly from that found in the cat. V1 layer 4 cells are largely similar to the the LGN cells that provide their input, being dominated by a single sign (ON or OFF) and being strongly modulated by sinusoidal gratings. Some layer 4 neurons, notably those near the edges of layer 4, exhibited increased orientation selectivity, and most layer 4 neurons exhibited a preference for lower temporal frequencies. Neurons in cortical layer 2/3 differ significantly from those in the LGN; most exhibited strong orientation tuning and both ON and OFF responses. The strength of orientation selectivity exhibited a notable sublaminar organization, with the strongest orientation tuned neurons in the most superficial parts of layer 2/3. Modulation indexes provide evidence for simple and complex cells in both layer 4 and layer 2/3. However, neurons with high modulation indexes were heterogenous in the spatial organization of ON and OFF responses, with many of them exhibiting unbalanced ON and OFF responses rather than well-segregated ON and OFF subunits. When compared to the laminar organization of V1 in other mammals, these data show that the process of natural selection can result in significantly altered structure/function relationships in homologous cortical circuits.