Vibrotactile sensitivity in active touch: effect of pressing force

An experiment was conducted to study the effects of force produced by active touch on vibrotactile perceptual thresholds. The task consisted in pressing the fingertip against a flat rigid surface that provided either sinusoidal or broadband vibration. Three force levels were considered, ranging from light touch to hard press. Finger contact areas were measured during the experiment, showing positive correlation with the respective applied forces. Significant effects on thresholds were found for vibration type and force level. Moreover, possibly due to the concurrent effect of large (unconstrained) finger contact areas, active pressing forces, and long duration stimuli, the measured perceptual thresholds are considerably lower than what previously reported in the literature

Extracellular matrix-cell interactions: Focus on therapeutic applications

Extracellular matrix (ECM) macromolecules together with a multitude of different molecules residing in the extracellular space play a vital role in the regulation of cellular phenotype and behavior. This is achieved via constant reciprocal interactions between the molecules of the ECM and the cells. The ECM-cell interactions are mediated via cell surface receptors either directly or indirectly with co-operative molecules. The ECM is also under perpetual remodeling process influencing cell-signaling pathways on its part. The fragmentation of ECM macromolecules provides even further complexity for the intricate environment of the cells. However, as long as the interactions between the ECM and the cells are in balance, the health of the body is retained. Alternatively, any dysregulation in these interactions can lead to pathological processes and finally to various diseases. Thus, therapeutic applications that are based on retaining normal ECM-cell interactions are highly rationale. Moreover, in the light of the current knowledge, also concurrent multi-targeting of the complex ECM-cell interactions is required for potent pharmacotherapies to be developed in the future

Does It Ping or Pong? Auditory and Tactile Classification of Materials by Bouncing Events

Two experiments studied the role of impact sounds and vibrations in classification of materials. The task consisted of feeling on an actuated surface and listening through headphones to the recorded feedback of a ping-pong ball hitting three flat objects respectively made of wood, plastic, and metal, and then identifying their material. In Experiment 1, sounds and vibrations were recorded by keeping the objects in mechanical isolation. In Experiment 2, recordings were taken while the same objects stood on a table, causing their resonances to fade faster due to mechanical coupling with the support. A control experiment, where participants listened to and touched the real objects in mechanical isolation, showed high accuracy of classification from either sounds (90% correct) or vibrations (67% correct). Classification of reproduced bounces in Experiments 1 and 2 was less precise. In both experiments, the main effect of material was statistically significant; conversely, the main effect of modality (auditory or tactile) was significant only in the control. Identification of plastic and especially metal was less accurate in Experiment 2, suggesting that participants, when possible, classified materials by longer resonance tails. Audio-tactile summation of classification accuracy was found, suggesting that multisensory integration influences the perception of materials. Such results have prospective application to the nonvisual design of virtual buttons, which is the object of our current research

Effects of vibration direction and pressing force on finger vibrotactile perception and force control

This paper reports about the effects of vibration direction and finger-pressing force on vibrotactile perception, with the goal of improving the effectiveness of haptic feedback on interactive surfaces. An experiment was conducted to assess the sensitivity to normal or tangential vibration at 250 Hz of a finger exerting constant pressing forces of 0.5 or 4.9 N. Results show that perception thresholds for normal vibration depend on the applied pressing force, significantly decreasing for the stronger force level. Conversely, perception thresholds for tangential vibrations are independent of the applied force, and approximately equal the lowest thresholds measured for normal vibration

Effects of vibration direction and pressing force on finger vibrotactile perception and force control

This paper reports about the effects of vibration direction and finger-pressing force on vibrotactile perception, with the goal of improving the effectiveness of haptic feedback on interactive surfaces. An experiment was conducted to assess the sensitivity to normal or tangential vibration at 250 Hz of a finger exerting constant pressing forces of 0.5 or 4.9 N. Results show that perception thresholds for normal vibration depend on the applied pressing force, significantly decreasing for the stronger force level. Conversely, perception thresholds for tangential vibrations are independent of the applied force, and approximately equal the lowest thresholds measured for normal vibration

Un Prototipo Di Pianoforte Digitale Con Feedback Vibrotattile

Questo lavoro presenta i risultati di due esperimenti percettivi compiuti su un prototipo di pianoforte digitale aumentato. L'obiettivo di entrambi gli esperimenti era studiare la percezione da parte del pianista di feedback vibrotattile sulla tastiera. Nel primo esperimento i soggetti coinvolti dovevano suonare liberamente al variare del feedback, e fornire un giudizio sulla qualit\ue0 percepita dello strumento in una griglia di cinque attributi: controllo dinamico, ricchezza, coinvolgimento, naturalezza, e preferenza complessiva. Nel secondo esperimento si \ue8 misurata l'accuratezza (in termini di tempo e di controllo dinamico) nell'esecuzione di una scala, al variare del feedback. I risultati mostrano una preferenza per le condizioni in cui \ue8 presente feedback vibrotattile, tuttavia per quanto riguarda l'accuratezza dell'esecuzione non sono state osservate differenze significative tra le diverse condizioni

Kupffer cell-monocyte communication is essential for initiating murine liver progenitor cell-mediated liver regeneration

Liver progenitor cells (LPCs) are necessary for repair in chronic liver disease because the remaining hepatocytes cannot replicate. However, LPC numbers also correlate with disease severity and hepatocellular carcinoma risk. Thus, the progenitor cell response in diseased liver may be regulated to optimize liver regeneration and minimize the likelihood of tumorigenesis. How this is achieved is currently unknown. Human and mouse diseased liver contain two subpopulations of macrophages with different ontogenetic origins: prenatal yolk sac-derived Kupffer cells and peripheral blood monocyte-derived macrophages. We examined the individual role(s) of Kupffer cells and monocyte-derived macrophages in the induction of LPC proliferation using clodronate liposome deletion of Kupffer cells and adoptive transfer of monocytes, respectively, in the choline-deficient, ethionine-supplemented diet model of liver injury and regeneration. Clodronate liposome treatment reduced initial liver monocyte numbers together with the induction of injury and LPC proliferation. Adoptive transfer of monocytes increased the induction of liver injury, LPC proliferation, and tumor necrosis factor-a production. Conclusion: Kupffer cells control the initial accumulation of monocyte-derived macrophages. These infiltrating monocytes are in turn responsible for the induction of liver injury, the increase in tumor necrosis factor-a, and the subsequent proliferation of LPCs

In epithelial cancers, aberrant COL17A1 promoter methylation predicts its misexpression and increased invasion

Background: Metastasis is a leading cause of death among cancer patients. In the tumor microenvironment, altered levels of extracellular matrix proteins, such as collagens, can facilitate the first steps of cancer cell metastasis, including invasion into surrounding tissue and intravasation into the blood stream. However, the degree of misexpression of collagen genes in tumors remains understudied, even though this knowledge could greatly facilitate the development of cancer treatment options aimed at preventing metastasis. Methods: We systematically evaluate the expression of all 44 collagen genes in breast cancer and assess whether their misexpression provides clinical prognostic significance. We use immunohistochemistry on 150 ductal breast cancers and 361 cervical cancers and study DNA methylation in various epithelial cancers. Results: In breast cancer, various tests show that COL4A1 and COL4A2 overexpression and COL17A1 (BP180, BPAG2) underexpression provide independent prognostic strength (HR = 1.25, 95% CI = 1.17–1.34, p = 3.03 × 10; HR = 1.18, 95% CI = 1.11–1.25, p = 8.11 × 10; HR = 0.86, 95% CI = 0.81–0.92, p = 4.57 × 10; respectively). Immunohistochemistry on ductal breast cancers confirmed that the COL17A1 protein product, collagen XVII, is underexpressed. This strongly correlates with advanced stage, increased invasion, and postmenopausal status. In contrast, immunohistochemistry on cervical tumors showed that collagen XVII is overexpressed in cervical cancer and this is associated with increased local dissemination. Interestingly, consistent with the opposed direction of misexpression in these cancers, the COL17A1 promoter is hypermethylated in breast cancer and hypomethylated in cervical cancer. We also find that the COL17A1 promoter is hypomethylated in head and neck squamous cell carcinoma, lung squamous cell carcinoma, and lung adenocarcinoma, in all of which collagen XVII overexpression has previously been shown. Conclusions: Paradoxically, collagen XVII is underexpressed in breast cancer and overexpressed in cervical and other epithelial cancers. However, the COL17A1 promoter methylation status accurately predicts both the direction of misexpression and the increased invasive nature for five out of five epithelial cancers. This implies that aberrant epigenetic control is a key driver of COL17A1 gene misexpression and tumor cell invasion. These findings have significant clinical implications, suggesting that the COL17A1 promoter methylation status can be used to predict patient outcome. Moreover, epigenetic targeting of COL17A1 could represent a novel strategy to prevent metastasis in patients

Decorin deficiency promotes hepatic carcinogenesis

Hepatocellular carcinoma represents one of the most-rapidly spreading cancers in the world. In the majority of cases, an inflammation-driven fibrosis or cirrhosis precedes the development of the tumor. During malignant transformation, the tumor microenvironment undergoes qualitative and quantitative changes that modulate the behavior of the malignant cells. A key constituent for the hepatic microenvironment is the small leucine-rich proteoglycan decorin, known to interfere with cellular events of tumorigenesis mainly by blocking various receptor tyrosine kinases (RTK) such as EGFR, Met, IGF-IR, PDGFR and VEGFR2. In this study, we characterized cell signaling events evoked by decorin deficiency in two experimental models of hepatocarcinogenesis using thioacetamide or diethyl nitrosamine as carcinogens. Genetic ablation of decorin led to enhanced tumor occurrence as compared to wild-type animals. These findings correlated with decreased levels of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 and a concurrent elevation in retinoblastoma protein phosphorylation via cyclin dependent kinase 4. Decreased steady state p21Waf1/Cip1 levels correlated with enhanced expression of transcription factor AP4, a known transcriptional repressor of p21Waf1/Cip1, and enhanced c-Myc protein levels. In addition, translocation of beta-catenin was a typical event in diethyl nitrosamine-evoked tumors. In parallel, decreased phosphorylation of both c-Myc and beta-catenin was observed in Dcn-/- livers likely due to the hindered GSK3beta-mediated targeting of these proteins to proteasomal degradation. We discovered that in a genetic background lacking decorin, four RTKs were constitutively activated (phosphorylated), including three known targets of decorin such as PDGFRalpha, EGFR, IGF-IR, and a novel RTK MSPR/RON. Our findings provide powerful genetic evidence for a crucial in vivo role of decorin during hepatocarcinogenesis as lack of decorin in the liver and hepatic stroma facilitates experimental carcinogenesis by providing an environment devoid of this potent pan-RTK inhibitor. Thus, our results support future utilization of decorin as an antitumor agent in liver cancer