Redundant Signals Research Articles

Multiple Plumage Ornaments as Signals of Intrasexual Communication in Golden‐Winged Warblers

AbstractAvian plumage represents some of the greatest diversity in integument coloration of all animals. Plumage signals are diverse in function, including those that allow for assessing potential mates or the mitigation of agonistic interactions between rivals. Many bird species possess multiple ornamental traits that have the potential to serve as multiple or redundant signals. For example, male golden‐winged warblers (Vermivora chrysoptera) have brilliant carotenoid‐based yellow crowns, melanin‐based black throats, and structurally based white patches on their outer tail feathers. Using a correlative approach, we investigated whether plumage ornaments have the potential to reliably signal ability to acquire higher quality territory, aggressive response to simulated territorial intrusions, and reproductive success. We found that both crown chroma and tail brightness were significantly related to habitat quality and aggression; more ornamented birds held territories with higher quality habitat and were less aggressive toward simulated conspecific stimuli. Older birds sang less threatening songs than younger birds and were more likely to sing their mate attraction song type (type 1) rather than songs typically reserved for agonistic interactions (type 2). Finally, despite our previous research demonstrating that habitat strongly predicts reproductive success in this warbler population, we found no evidence of a direct link between ornamentation and reproductive success. Overall, these data suggest that younger males, and those with lower quality ornaments, compensate with more aggressive behaviors. Additional research is needed to investigate the dynamics between behavioral traits and ornaments to better understand complex signaling and how golden wing signals function in conspecific interactions (male–male interactions and mate‐choice).

Multisensory Decisions: the Test of a Race Model, Its Logic, and Power

The use of separate multisensory signals is often beneficial. A prominent example is the speed-up of responses to two redundant signals relative to the components, which is known as the redundant signals effect (RSE). A convenient explanation for the effect is statistical facilitation, which is inherent in the basic architecture of race models (Raab, 1962,Trans. N. Y. Acad. Sci.24, 574–590). However, this class of models has been largely rejected in multisensory research, which we think results from an ambiguity in definitions and misinterpretations of the influential race model test (Miller, 1982,Cogn. Psychol.14, 247–279). To resolve these issues, we here discuss four main items. First, we clarify definitions and ask how successful models of perceptual decision making can be extended from uni- to multisensory decisions. Second, we review the race model test and emphasize elements leading to confusion with its interpretation. Third, we introduce a new approach to study the RSE. As a major change of direction, our working hypothesis is that the basic race model architecture is correct even if the race model test seems to suggest otherwise. Based on this approach, we argue that understanding the variability of responses is the key to understand the RSE. Finally, we highlight the critical role of model testability to advance research on multisensory decisions. Despite being largely rejected, it should be recognized that race models, as part of a broader class of parallel decision models, demonstrate, in fact, a convincing explanatory power in a range of experimental paradigms. To improve research consistency in the future, we conclude with a short checklist for RSE studies.

Event-Triggered H∞ Proportional-Integral Output Feedback Tracking Control and Its Application to Ducted Rocket Engine

This paper deals with the problem of $H_\infty $ proportional–integral (PI) output feedback tracking control for a ducted rocket engine when event-triggering mechanism is incorporated. We determine necessary samplings of the feedback signal by constructing predefined event-triggering condition that can reduce redundant signal transmission and updates. Specifically, the mathematical model of ducted rocket is first introduced and its control problem is described. Then, for control design, an output-based periodic event-triggering scheme is provided. Particularly, a variable built by the exogenous disturbance and reference signal is added in the event-triggering condition to adjust triggering frequency and $H_\infty $ output tracking performance. Moreover, to facilitate system performance analysis, a time-delay closed-loop model is established with the PI controller. By using the Lyapunov–Krasovskii functional method, a sufficient condition is further provided to guarantee the $H_\infty $ output tracking performance. Meanwhile, the influence of the event-triggered control on the system performance analysis is clarified. Finally, the proposed control method is applied to the ducted rocket control model, and simulation results demonstrate its effectiveness.

Development of high-yield and high-reliability design for high-performance ultra large scale 3DLSI processor

With LSI micro-fabrication technology reaching its scaling limits, miniaturizing LSIs based on Moore's Law is unable to satisfy the CPU/memory module performance for high-speed, low-power, high-end servers, an alternative integration technology such as three-dimensional integration (3DI) is becoming mainstream. With the development of 3D stacked high-performance processors, specifications that excel in power consumption (200 to 300 W), heat generation, number of electrodes and large die area are required, necessitating a major technical leap from the conventional 3D packaging technologies. A guarantee of reliability and the yield loss is very severe, because of the high-performance processor's needing 30 times or more the both die area and the number of pins compared with the combinational high band width memory stacking. We were the first to verify 3D logic device operation by integrating the following technologies: through-silicon via (TSV) technologies, in which signals are connected in the shortest distance between a top and bottom stacked ultra-large die area processor die; novel redundancy signal transmission design technology; super multi-pins connection technology for high-yield signal transmission with high bandwidth; and high reliability solder joint materials considering power integrity (PI) between stacked dies. To achieve the high-yield TSV connection, the TSV redundant circuit was designed and installed into the stack dies due to the difficulty of the avoidance of defect density (D0) increasing such as large die area. Novel logic macro design with one redundant TSV for 16 signal node enabled the accurate switching selection to redundant defective TSV by using the execution of a pre-test sequence to find bad TSV. In addition, a redundant logic circuit of top and bottom interconnect is a design that gives control signal the redundancy. As a result, the higher operation guarantee was given to the operation execution of controlling circuit. This redundant circuit design technology demonstrated without yield loss of TSV interconnect. For high-reliability fine pitch bump (40-μm pitch) and 10-μm TSV interconnect formation technologies, a large-current, high-heat dissipation and high-precision stacking technology were required. We have developed a process technology for fine-pitch micro bump junctions supporting large current and high-precision I/O bumps stacking dies with 200,000 or more pins using by Ni-Sn intermetallic compound (IMC) solder materials. We also have developed a high accuracy of large die stacking process to be used in fine TSV in which large amounts of current flow and connection terminal sections on dies, achieving stable supply of 300-Watt-class power consumption. Compared with the current density for a 10-year guaranteed lifetime, the case of IMC alloy joining achieves a current density resistance of 4 times more than that of conventional Sn-Ag solder materials, and this has proven to be effective for a high-performance processor. By developing 3DLSI packaging technology compatible with ultra large dies for a high-performance processor and overcoming the issue of yield and reliability, we have achieved a redundancy design technology and micro bump materials of high-yield at product level stacked logic processor with over 750 mm square as full reticle shot size. In this paper, we will discuss the important key redundancy TSV design method and micro bump material technologies; in 3D packaging technology for realizing high-performance ultra large scale processor.

Adaptive mechanisms of resistance to anti-neoplastic agents.

Intrinsic and acquired resistance to conventional and targeted therapeutics is a fundamental reason for treatment failure in many cancer patients. Targeted approaches to overcome chemoresistance as well as resistance to targeted approaches require in depth understanding of the underlying molecular mechanisms. The anti-cancer activity of a drug can be limited by a broad variety of molecular events at different levels of drug action in a cell-autonomous and non-cell-autonomous manner. This review summarizes recent insights into the adaptive mechanisms used by tumours to resist therapy including cellular phenotypic plasticity, dynamic alterations of the tumour microenvironment, activation of redundant signal transduction pathways, modulation of drug target expression levels, and exploitation of pro-survival responses.

Positive association between vocal and facial attractiveness in women but not in men: A cross-cultural study

Various species use multiple sensory modalities in the communication processes. In humans, female facial appearance and vocal display are correlated and it has been suggested that they serve as redundant markers indicating the bearer’s reproductive potential and/or residual fertility. In men, evidence for redundancy of facial and vocal attractiveness is ambiguous. We tested the redundancy/multiple signals hypothesis by correlating perceived facial and vocal attractiveness in men and women from two different populations, Brazil and the Czech Republic. We also investigated whether facial and vocal attractiveness are linked to facial morphology. Standardized facial pictures and vocal samples of 86 women (47 from Brazil) and 81 men (41 from Brazil), aged 18–35, were rated for attractiveness by opposite-sex raters. Facial and vocal attractiveness were found to positively correlate in women but not in men. We further applied geometric morphometrics and regressed facial shape coordinates on facial and vocal attractiveness ratings. In women, facial shape was linked to their facial attractiveness but there was no association between facial shape and vocal attractiveness. In men, none of these associations was significant. Having shown that women with more attractive faces possess also more attractive voices, we thus only partly supported the redundant signal hypothesis.

Combinatorial Effect of HDAC6i and Ibrutinib Therapy in CLL Murine Model

Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor is now FDA approved for front line and relapsed and refractory CLL. Although this drug has been shown to be successful in controlling the disease, most patients only reach partial responses (PR) likely secondary to activation of alternative and redundant BCR signaling pathways. In the past several years, epigenetic changes in CLL have gained special attention (Tong et al 2010) because of their intricate interplay with previously described genetic events and its active role in the regulation of pathogenesis and immune-related pathways (Stilgenbauer et al 2002). Recent publications have described the differential expression of specific HDACs in CLL, as well as the impact of global histone deacetylase activity and its relation with progression and overall survival (Van Damme et al 2014, Yang et al 2015).Previously, we had reported that expression of HDAC6 is increased in CLL patient samples and cell lines. We have also demonstrated that modulation of this HDAC, effects cell proliferation and viability in CLL cell lines. Additionally, treatment with HDAC6i (ACY-738 - a potent and selective HDAC6i) demonstrated increased overall survival in euTCL1 mice, a murine CLL model. Treatment of euTCL1 mice (both adoptive transfer and aging model) with ACY-738 as a single agent resulted in 1) overall survival advantage, 2) reduction of tumor burden, 3) reduction in PD-L1 expression in the malignant B cell population and 4) decreased circulating Treg numbers. Furthermore, we demonstrated that in an in vitrostudy, treatment of HDAC6i with ibrutinib in CLL cell lines render strong synergistic cell killing. In our current study of this combinatorial approach, using the adoptive transfer euTCL1 model receiving Ibrutinib in drinking water and ACY-738 in feed, we demonstrate a further decrease in tumor burden when compared to single agent treatment with either compound alone. This observed effect on tumor burden occurred in conjunction with decreases in co-inhibitory molecules and circulating Treg frequency. The combination was well tolerated and no significant toxicity was observed.Since aberrant over-expression of HDAC6 in CLL cell lines and patient's samples have already been demonstrated (Van Damme et al 2012, Sahakian et al 2012) we sought to understand its mechanistic role in BCR survival pathways of CLL. Our studiesin normal B cells isolated from C57BL/6 and HDAC6KO mice, demonstrated a reduction in phosphorylation of BTK, ERK, and AKT. Similar results were observed when we compared euTCL1 to euTCL1/HDAC6KO B cells. Additionally,we observed decreased phosphorylation of ERK and SYK in MEC2-HDAC6KD cells when compared to parental control CLL cells. Moreover, RNA-Seq studies of the eu-TCL1/HDAC6KO versus euTCL1 B cells showed several key BCR signaling proteins altered by the deletion of HDAC6.In conclusion, these results from our preclinical CLL models suggest that combinatorial therapy of Ibrutinib plus HDAC6i show synergistic inhibition of BCR signaling and therefore a better overall treatment outcome. DisclosuresQuayle:Acetylon Pharmaceuticals: Employment, Equity Ownership. Jones:Acetylon Pharmaceuticals, Inc.: Employment, Equity Ownership. Pinilla-Ibarz:Gilead: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy, Speakers Bureau; Novartis: Consultancy; Abbvie: Consultancy, Speakers Bureau; Novartis: Consultancy; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Speakers Bureau.

Adaptive Reactivation of Signaling Pathways As a Novel Mechanism of Resistance to JAK Inhibitors in Ph-like ALL

Background:Ph-like ALL was first described in 2009 and was accepted as a novel B-ALL subgroup by the WHO in 2016. Ph-like ALL is characterized by different chromosomal rearrangements involving CRLF2, ABL1, JAK2, and EPOR. In addition, mutations in PAX5, IKZF1, and JAK2 are very common. The gene expression profile of this disease is very similar to Ph+ ALL which is characterized by the BCR-ABL1 oncogene. We have previously shown that Ph-like ALL is a high risk disease with a poor prognosis and constitutive activation of cytokine receptor signaling pathway (Tasian et al., submitted). Our current study is focusing on redundant signaling activation in Ph-like ALL that allows the cells to survive cytokine receptor inhibition.Results:We and others have shown that Ph-like ALL have constitutive activation of the cytokine receptor signaling pathway evident by high expression levels of pSTAT5. Xenotransplantation models of Ph-like ALL show a decrease in leukemia burden when treated with Ruxolitinib a JAK1/2 inhibitor. However, all mice ultimately succumb to the disease, demonstrating that Ph-like ALL does not demonstrate oncogene addiction. To understand these results, we have initially used Ph-like ALL cell lines. Ruxolitinib treatment of such cell lines decreases survival but does not eliminate all viable cells. In addition, Ruxolitinib leads to down regulation of pSTAT5, pSTAT3, pAKTT308 as well as pAKTS473. To further study the mechanism of resistance to JAK inhibition we performed a time course experiments and found that as early as 48-72 hours after the initial JAK inhibitor treatment Ph-like ALL cell are able to reactivate pSTAT5 and pAKT. This effect was not due to drug inactivation. Based on this observation, we hypothesized that adaptive signaling through PI3 kinase protects Ph-like ALL cells from cell death. Interestingly, PI3K inhibition (Idelalisib) alone had only a minor effect on cell viability and cell proliferation and the Ph-like ALL cells were able to reactivate the signaling network within 48-72h. Dual treatment with JAK1/2 and PI3 kinase inhibition significantly increased the apoptotic effect and stopped proliferation. In addition, the dual treatment induced a long lasting inhibitory effect with no signs of pAKT reactivation. Strikingly, combining JAK and PI3K inhibition with Methotrexate an antimetabolite that is used for the treatment of ALL patients significantly increased the apoptotic effect of the combinatory treatment. Overall, these results demonstrate that adaptive signaling with reactivation of the PI3K signaling cascade protects Ph-like ALL cells from inhibition of JAK kinases and suggests that dual kinase inhibitor therapy may increase response in the clinic. Experiments studying how reactivation occurs and the in vivo response to dual JAK-PI3K inhibition are in progress.Clinical relevance:Older patients (>40 years) often do not qualify for induction chemotherapy as they do not tolerate high doses of chemotherapy regimens and are therefore in clinical need of alternative treatment regimens that can improve their clinical outcome. While children with ALL currently have a 5-year survival rate of 90% adults especially older adults have a very poor clinical outcome with survival rates of about 40%. We therefore combined JAK1/2 and PI3K inhibitory treatments with methotrexate a frequently used antimetabolite that is well tolerated by older patients. Strikingly, the combinatory treatment had a strong effect on cell viability and represents so far the first study using specific signaling inhibitors combined with an antimetabolite treatment in Ph-like ALL.Conclusion:These findings identify that Ph-like ALL are able to reestablish their signaling networks. Based on our finding it is important to target more than one signaling pathways to fully inhibit cell proliferation and cell survival. We propose to treat Ph-like ALL patients with a combinatory treatment of JAK1/2 and PI3K inhibitor and currently used antimetabolite drugs to reduce the risk of relapse and to improve the clinical outcome of patients with Ph-like ALL. DisclosuresPerl:Seattle Genetics: Consultancy; Actinium Pharmaceuticals, Inc.: Research Funding.

Seeing the Forest for the Trees.

Although tens, or even hundreds, of molecular or pharmacological interventions have been shown to affect the course of heart failure in animal models, few have translated to clinical therapies. This likely stems from the fact that biological robustness and flexibility are conferred by the evolution of redundant or adaptive signaling and gene expression pathways, which lead to not one, but multiple “master” control nodes in the network, making it difficult to pinpoint the most effective single target intervention. Systems biology tools and approaches are helping to define how the heart is remodeled during stress and to define important control points, even as they further highlight the scope of our ignorance. Applying these analyses to time-dependent changes in heart failure is essential to understand critical thresholds for aberrant nonlinear cellular responses that lead to emergent events, such as sudden cardiac death. Trying to understand the mechanisms behind heart failure often brings to mind the analogy of science as “a hungry furnace that must be fed logs from the forests of ignorance that surrounds us. In the process, the clearing we call knowledge expands, but the more it expands, the longer its perimeter and the more ignorance comes into view.”1 Extending this further, we scientists often act as independent woodcutters in our own little clearings, either focusing our reductionist minds on taking the tree down like a leafcutter ant rather than by chainsaw, or attempting to frame our favorite target as the master key that unlocks the secret to curing the disease (a must to enchant those study section reviewers). From the literature, it seems that there are many such master keys that prevent or reverse cardiac dysfunction related to heart failure (HF) in animal models—fixing various defects in SR Ca2+ uptake, ryanodine receptor leak, repolarization reserve, oxidative stress, nitric …

Host cancelation‐based spread spectrum watermarking for audio anti‐piracy over Internet

AbstractThis paper addresses the audio piracy problem over Internet by tweaking data redundancy of host media signal for optimized embedding and extraction of spread spectrum watermarking. In particular, we take into account a special feature that host audio signals have the short‐time stationary property and their major power can be removed using linear prediction filter. By combining the redundancy removing and the improved spread spectrum modulation, host interference is canceled with minimized embedding distortion to the host audio. The data redundancy removing is also applied at the receiver to achieve matched filtering and improved performance. Experiments based on real audio signals show that our proposed scheme performs robustly against various kinds of channel attacks while maintaining high extraction performance. Copyright © 2016 John Wiley & Sons, Ltd.

Gs/Gi Regulation of Bone Cell Differentiation: Review and Insights from Engineered Receptors.

G-protein coupled receptors (GPCRs) and their ligands are critical for normal osteoblast formation and function. GPCRs mediate a wide variety of biological processes and are activated by multiple types of extracellular signals, ranging from photons to small molecules to peptides. GPCRs signal through a select number of canonical pathways: the Gs and Gi pathways increase or decrease intracellular cAMP levels, respectively, by acting on adenylate cyclase, while the Gq pathway increases intracellular calcium by activating phospholipase C. In addition, non-canonical GPCR pathways such as β-arrestin activation are important for osteoblast function. Since many cells express multiple GPCRs, and each individual GPCR may activate multiple signaling pathways, the resulting combinatorial signal provides a mechanism for regulating complex biological processes and effector functions. However, the wide variety of GPCRs, the possibility of multiple receptors acting with signaling redundancy, and the possibility of an individual GPCR activating multiple signaling pathways, also pose challenges for elucidating the role of a particular GPCR. Here, we briefly review the roles of Gs and Gi GPCR signaling in osteoblast function. We describe the successful application of a strategy for directly manipulating the Gs and Gi pathways using engineered receptors. These powerful tools will allow further elucidation of the roles of GPCR signaling in specific lineages of osteoblastic cells, as well as in non-osteoblast cells, all of which remain critical areas of active research.

Evidence for the Redundant Signals Effect in Detection of Categorical Targets

Evidence for the Redundant Signals Effect in Detection of Categorical Targets

Redundant information processing techniques comparison for differential vibratory gyroscope

Advantages of differential Coriolis vibratory gyroscope of the new type with two measuring channels of angle rate with opposite signs that provides redundant measuring information about angle rate are analyzed. Comparative analysis of four different techniques of redundant signals processing including technology of “virtual” gyro signals processing in application to the differential vibratory gyroscope is carried out. Importance of creation of redundant information processing techniques is caused by distinction of the differential vibratory gyroscope from other micro­electro­mechanical gyros, for example, tuning fork gyro, in that it has two output signals, which come from the single resonator and correspond to angle rates with opposite signs. As a result redundant output information processing techniques were obtained. This information comes from the differential vibratory gyroscope output and is formed by subtracting of two measuring channel signals. The algorithm of “virtual” gyro redundant output information processing was modified. The algorithm differs from known ones by calculation of inter­channel correlation matrix in on­line manner. This leads to decrease of angle rate measuring random error and to decrease overshoot in conditions of abrupt change of angle rate. The obtained results are important and useful for application of differential vibratory gyroscopes in stabilization systems and angular motion control. This is caused by high requirements to accuracy and ability to function in hash environment.

Human tissue engineering allows the identification of active miRNA regulators of glioblastoma aggressiveness.

Glioblastoma multiforme (GBM) is among the most aggressive cancers associated with massive infiltration of peritumoral parenchyma by migrating tumor cells. The infiltrative nature of GBM cells, the intratumoral heterogeneity concomitant with redundant signaling pathways likely underlie the inability of conventional and targeted therapies to achieve long-term remissions. In this respect, microRNAs (miRNAs), which are endogenous small non-coding RNAs that play a role in cancer aggressiveness, emerge as possible relevant prognostic biomarkers or therapeutic targets for treatment of malignant gliomas. We previously described a tissue model of GBM developing into a stem cell-derived human Engineered Neural Tissue (ENT) that allows the study of tumor/host tissue interaction. Combined with high throughput sequencing analysis, we took advantage of this human and integrated tissue model to understand miRNAs regulation. Three miRNAs (miR-340, -494 and -1293) active on cell proliferation, adhesion to extracellular matrix and tumor cell invasion were identified in GBM cells developing within ENT, and also confirmed in GBM biopsies. The components of miRNAs regulatory network at the transcriptional and the protein level have been also revealed by whole transcriptome analysis and Tandem Mass Tag in transfected GBM cells. Notably, miR-340 has a clinical relevance and modulates the expression of miR-494 and -1293, emphasizing its biological significance. Altogether, these findings demonstrate that human tissue engineering modeling GBM development in neural host tissue is a suitable tool to identify active miRNAs. Collectively, our study identified miR-340 as a strong modulator of GBM aggressiveness which may constitute a therapeutic target for treatment of malignant gliomas.

Dynamic Multisensory Integration: Somatosensory Speed Trumps Visual Accuracy during Feedback Control.

Recent advances in movement neuroscience have consistently highlighted that the nervous system performs sophisticated feedback control over very short time scales (<100 ms for upper limb). These observations raise the important question of how the nervous system processes multiple sources of sensory feedback in such short time intervals, given that temporal delays across sensory systems such as vision and proprioception differ by tens of milliseconds. Here we show that during feedback control, healthy humans use dynamic estimates of hand motion that rely almost exclusively on limb afferent feedback even when visual information about limb motion is available. We demonstrate that such reliance on the fastest sensory signal during movement is compatible with dynamic Bayesian estimation. These results suggest that the nervous system considers not only sensory variances but also temporal delays to perform optimal multisensory integration and feedback control in real-time. Numerous studies have demonstrated that the nervous system combines redundant sensory signals according to their reliability. Although very powerful, this model does not consider how temporal delays may impact sensory reliability, which is an important issue for feedback control because different sensory systems are affected by different temporal delays. Here we show that the brain considers not only sensory variability but also temporal delays when integrating vision and proprioception following mechanical perturbations applied to the upper limb. Compatible with dynamic Bayesian estimation, our results unravel the importance of proprioception for feedback control as a consequence of the shorter temporal delays associated with this sensory modality.

Low Complexity Joint Blind Equalization and CFO Estimation for MC-CDMA System

Based on the orthogonality between the used and the unused spreading codes (excess codes) subspaces in one hand and on the restoration of guard interval redundancy of Multicarrier Code Division Multiple Access signal in other hand, we propose joint Carrier Frequency Offset and time domain equalizer estimators. A major difficulty arises from the highly complexity of these methods. Use of an approximation method or an adaptive algorithm has been popular approach to ease problem solving. Our derived methods are found to be good in terms of estimation accuracies, computation complexity, and convergence speed when compared to the block processing algorithms.

The synergistic induction of bone formation by the osteogenic proteins of the TGF-β supergene family.

The momentum to compose this Leading Opinion on the synergistic induction of bone formation suddenly arose when a simple question was formulated during a discussion session on how to boost the often limited induction of bone formation seen in clinical contexts. Re-examination of morphological and molecular data available on the rapid induction of bone formation by the recombinant human transforming growth factor-β3 (hTGF-β3) shows that hTGF-β3 replicates the synergistic induction of bone formation as invocated by binary applications of hOP-1:hTGF-β1 at 20:1 by weight when implanted in heterotopic sites of the rectus abdominis muscle of the Chacma baboon, Papio ursinus. The rapid induction of bone formation in primates by hTGF-β3 may stem from bursts of cladistic evolution, now redundant in lower animal species but still activated in primates by relatively high doses of hTGF-β3. Contrary to rodents, lagomorphs and canines, the three mammalian TGF-β isoforms induce rapid and substantial bone formation when implanted in heterotopic rectus abdominis muscle sites of P.ursinus, with unprecedented regeneration of full thickness mandibular defects with rapid mineralization and corticalization. Provocatively, thus providing potential molecular and biological rationales for the apparent redundancy of osteogenic molecular signals in primates, binary applications of recombinant human osteogenic protein-1 (hOP-1) with low doses of hTGF-β1 and -β3, synergize to induce massive ossicles in heterotopic rectus abdominis, orthotopic calvarial and mandibular sites of P.ursinus. The synergistic binary application of homologous but molecularly different soluble molecular signals has indicated that per force several secreted molecular signals are required singly, synchronously and synergistically to induce optimal osteogenesis. The morphological hallmark of the synergistic induction of bone formation is the rapid differentiation of large osteoid seams enveloping haematopoietic bone marrow that forms by day 15 in heterotopic rectus abdominis sites. Synergistic binary applications also induce the morphogenesis of rudimentary embryonic growth plates indicating that the "memory" of developmental events in embryo can be redeployed postnatally by the application of morphogen combinations. Synergistic binary applications or single relatively high doses of hTGF-β3 have shown that hTGF-β3 induces bone by expressing a variety of inductive morphogenetic proteins that result in the rapid induction of bone formation. Tissue induction thus invocated singly by hTGF-β3 recapitulates the synergistic induction of bone formation by binary applications of hTGF-β1 and -β3 isoforms with hOP-1. Both synergistic strategies result in the rapid induction and expansion of the transformed mesenchymal tissue into large corticalized heterotopic ossicles with osteoblast-like cell differentiation at the periphery of the implanted reconstituted specimens with "tissue transfiguration" invivo. Molecularly, the rapid induction of bone formation by binary applications of hOP-1 and hTGF-β3 or by hTGF-β3 applied singly resides in the up-regulation of selected genes involved in tissue induction and morphogenesis, Osteocalcin, RUNX-2, OP-1, TGF-β1 and -β3 with however the noted lack of TGF-β2 up-regulation.

Abstract 1449: In vivo targeted silencing of CCR1 and CCR5 repolarizes pro-tumoral myeloid cells in retinoblastoma positive neutrophils with a strong anti-tumor activity

Abstract Introduction: Depending on their polarization, myeloid cells can either promote or restrain tumor progression. By secreting myelopoietic factors tumours promote myeloid cells polarization toward a phenotype that provides immune protection and that stimulate neoplastic cells growth, invasiveness, and metastasis. Chemokines and their cognate receptors are thought to play a key role in myeloid cell trafficking, however, their study in vivo is hindered by their signal redundancy and integration. Methods: By taking advantage of a newly developed nanoplatform that allows the in vivo preferential transfection of tumor infiltrating myeloid cells (TIMC, aka Myeloid derived suppressor cells, MDSC, and tumor associated macrophages, TAM), we evaluated the effect of CCR-1, CCR-2, CCR-4, CCR-5 and/or CCR-7 silencing on TAMC trafficking, phenotype, and function. Results: While CCR-4 and -7 targeted silencing did not affect tumor progression, simultaneous silencing of CCR-1 and CCR-5 significantly restrained tumor growth and greatly modifies tumor micro-environment. Mechanistic in vivo and in vitro analysis surprisingly indicate that myeloid cell trafficking was not altered whereas myeloid cell polarization was. In particular, CCR-1 and CCR-5 blockade restrained MDSC differentiation and promote the accumulation of retinoblastoma positive, neutrophil-like cells with a strong tumoricidal activity. Discussion: Our data indicate that CCR-1 and CCR-5 engagement (most likely via CCL-3 and CCL-4) is necessary for the pro-tumoral polarization of myeloid cells in cancer. Our findings not only improve our understanding of myeloid cells differentiation in cancer but, also, strongly suggest that targeted inhibition of CCR1 and CCR5 on TIMC can be a new and effective anti-tumor immune-therapeutic strategy that convert pro-tumoral MDSCs into tumoricidal neutrophils. Citation Format: Serena Zilio, Jennifer Vella, Adriana De La Fuente, Vincenzo Bronte, Emilia Mazza, Silvio Bicciato, Paolo Serafini. In vivo targeted silencing of CCR1 and CCR5 repolarizes pro-tumoral myeloid cells in retinoblastoma positive neutrophils with a strong anti-tumor activity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1449.

Continuous wavelet transform for ferroresonance detection in power systems

Wavelet transforms, such as Continuous Wavelet Transform (CWT) create numerous signals based on scale coefficients after decomposition. This entire signal set and their subsets with regard to a chosen function can actually be used to reconstruct redundant representations of the real signal in such a manner that different signal characteristics like anomalies can be detected. This study aims to provide another perspective to wavelet transform studies in terms of the redundancy feature which comes from wavelet type and scale number as well as transform type itself. Consequently, a partial feature construction (PFC) method has been introduced to select the appropriate signal subset which will reconstruct redundant signals for anomaly detection. As a real-world application, ferroresonance data generated by a MATLAB-Simulink model have been used. PFC method has been applied to a subset of decomposed ferroresonance data from CWT, and it has been investigated with different function scenarios. As a result, redundant signals reconstructed by specific functions in PFC have not only allowed detecting ferroresonance phenomenon, but they also made it clearer to observe physical ferroresonance behavior.

Tropical wrens rely more on acoustic signals than visual signals for inter- and intraspecific discrimination

Animals may use multiple signalling modalities to discriminate between conspecific versus heterospecific animals, or between individuals that represent a threat versus a mating opportunity. Multimodal signals used in intra- and interspecific discrimination can serve as redundant signals, or each modality may convey unique information. Furthermore, signals in different modalities may show different transmission properties through different habitats. In this study we investigated how two congeneric wrens, rufous-and-white wrens, Thryophilus rufalbus, and banded wrens, Thryophilus pleurostictus, use acoustic and visual signals for species discrimination in tropical forest habitats. We coupled song playback experiments with visual models to assess the importance of these signals, both in combination and in isolation. We assessed vegetation density in the territories of both species to assess whether more densely vegetated territories influence the use of visual signals. We presented both rufous-and-white wrens and banded wrens with conspecific and congeneric song treatments, model treatments and song-accompanied-by-model treatments. We found that both species responded strongly to song and song-accompanied-by-model treatments, but showed little or no response when the model was presented alone. These results suggest that wrens rely heavily on acoustic signals and very little on visual signals for discrimination. The species differed in their response to conspecific and congeneric trials, with rufous-and-white wrens showing little response to the congeneric trials but banded wrens responding strongly to both conspecific and congeneric trials. The asymmetrical response to the playback trials suggests that there may be a social dominance relationship between these two species, with rufous-and-white wrens being dominant over banded wrens. No previous studies have investigated the relative importance of acoustic and visual signals in males and females for species discrimination. Our results suggest that acoustic signals are more important than visual signals for inconspicuous animals living in dense environments.