Nothing more than a pair of curvatures: A common mechanism for the detection of both radial and non-radial frequency patterns.

Radial frequency (RF) patterns, which are sinusoidal modulations of a radius in polar coordinates, are commonly used to study shape perception. Previous studies have argued that the detection of RF patterns is either achieved globally by a specialized global shape mechanism, or locally using as cue the maximum tangent orientation difference between the RF pattern and the circle. Here we challenge both ideas and suggest instead a model that accounts not only for the detection of RF patterns but also for line frequency patterns (LF), i.e. contours sinusoidally modulated around a straight line. The model has two features. The first is that the detection of both RF and LF patterns is based on curvature differences along the contour. The second is that this curvature metric is subject to what we term the Curve Frequency Sensitivity Function, or CFSF, which is characterized by a flat followed by declining response to curvature as a function of modulation frequency, analogous to the modulation transfer function of the eye. The evidence that curvature forms the basis for detection is that at very low modulation frequencies (1-3 cycles for the RF pattern) there is a dramatic difference in thresholds between the RF and LF patterns, a difference however that disappears at medium and high modulation frequencies. The CFSF feature on the other hand explains why thresholds, rather than continuously declining with modulation frequency, asymptote at medium and high modulation frequencies. In summary, our analysis suggests that the detection of shape modulations is processed by a common curvature-sensitive mechanism that is subject to a shape-frequency-dependent transfer function. This mechanism is independent of whether the modulation is applied to a circle or a straight line

Modeling probability and additive summation for detection across multiple mechanisms under the assumptions of signal detection theory.

Many studies have investigated how multiple stimuli combine to reach threshold. There are broadly speaking two ways this can occur: additive summation (AS) where inputs from the different stimuli add together in a single mechanism, or probability summation (PS) where different stimuli are detected independently by separate mechanisms. PS is traditionally modeled under high threshold theory (HTT); however, tests have shown that HTT is incorrect and that signal detection theory (SDT) is the better framework for modeling summation. Modeling the equivalent of PS under SDT is, however, relatively complicated, leading many investigators to use Monte Carlo simulations for the predictions. We derive formulas that employ numerical integration to predict the proportion correct for detecting multiple stimuli assuming PS under SDT, for the situations in which stimuli are either equal or unequal in strength. Both formulas are general purpose, calculating performance for forced-choice tasks with M alternatives, n stimuli, in Q monitored mechanisms, each subject to a non-linear transducer with exponent τ. We show how the probability (and additive) summation formulas can be used to simulate psychometric functions, which when fitted with Weibull functions make signature predictions for how thresholds and psychometric function slopes vary as a function of τ, n, and Q. We also show how one can fit the formulas directly to real psychometric functions using data from a binocular summation experiment, and show how one can obtain estimates of τ and test whether binocular summation conforms more to PS or AS. The methods described here can be readily applied using software functions newly added to the Palamedes toolbox

Rejecting probability summation for radial frequency patterns, not so Quick!

Radial frequency (RF) patterns are used to assess how the visual system processes shape. They are thought to be detected globally. This is supported by studies that have found summation for RF patterns to be greater than what is possible if the parts were being independently detected and performance only then improved with an increasing number of cycles by probability summation between them. However, the model of probability summation employed in these previous studies was based on High Threshold Theory (HTT), rather than Signal Detection Theory (SDT). We conducted rating scale experiments to investigate the receiver operating characteristics. We find these are of the curved form predicted by SDT, rather than the straight lines predicted by HTT. This means that to test probability summation we must use a model based on SDT. We conducted a set of summation experiments finding that thresholds decrease as the number of modulated cycles increases at approximately the same rate as previously found. As this could be consistent with either additive or probability summation, we performed maximum-likelihood fitting of a set of summation models (Matlab code provided in our Supplementary material) and assessed the fits using cross validation. We find we are not able to distinguish whether the responses to the parts of an RF pattern are combined by additive or probability summation, because the predictions are too similar. We present similar results for summation between separate RF patterns, suggesting that the summation process there may be the same as that within a single RF

The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions

C-Kit (CD117), the receptor for the stem cell factor, a growth factor for melanocyte migra- tion and proliferation, has shown differential immunostaining in various benign and malig- nant melanocytic lesions. The purpose of this study is to compare c-Kit immunostaining in benign nevi and in primary and metastatic malignant melanomas, to determine whether c-Kit can aid in the differential diagnosis of these lesions. c-Kit immunostaining was per- formed in 60 cases of pigmented lesions, including 39 benign nevi (5 blue nevi, 5 intra- dermal nevi, 3 junctional nevi, 15 cases of pri- mary compound nevus, 11 cases of Spitz nevus), 18 cases of primary malignant melanoma and 3 cases of metastatic melanoma. The vast majority of nevi and melanomas examined in this study were posi- tive for c-Kit, with minimal differences between benign and malignant lesions. C-Kit cytoplasmatic immunoreactivity in the intraepidermal proliferating nevus cells, was detected in benign pigmented lesions as well as in malignant melanoma, increasing with the age of patients (P=0.007) in both groups. The patient’s age at presentation appeared to be the variable able to cluster benign and malignant pigmented lesions. The percentage of c-Kit positive intraepidermal nevus cells was better associated with age despite other vari- ables (P=0.014). The intensity and percentage of c-Kit positivity in the proliferating nevus cells in the dermis was significantly increased in malignant melanocytic lesions (P=0.015 and P=0.008) compared to benign lesions (compound melanocytic nevi, Spitz nevi, intradermal nevi, blue nevi). Immunostaning for c-Kit in metastatic melanomas was nega- tive. Interestingly in two cases of melanoma occurring on a pre-existent nevus, the melanoma tumor cells showed strong cytoplas- matic and membranous positivity for c-kit, in contrast with the absence of any immunoreac- tivity in pre-existent intradermal nevus cells. C-Kit does not appear to be a strong immuno- histochemical marker for distinguishing melanoma from melanocytic nevi, if we consid- er c-Kit expression in intraepidermal prolifer- ating cells. The c-Kit expression in proliferat- ing melanocytes in the dermis could help in the differential diagnosis between a superfi- cial spreading melanoma (with dermis inva- sion) and a compound nevus or an intradermal nevus. Finally, c-Kit could be a good diagnostic tool for distinguishing benign compound nevi from malignant melanocytic lesions with der- mis invasion and to differentiate metastatic melanoma from primary melanoma

CT attenuation analysis of carotid intraplaque hemorrhage

Background and Purpose: Intraplaque hemorrhage is considered a leading parameter of carotid plaque vulnerability. Our purpose was to assess the CT characteristics of intraplaque hemorrhage with histopathologic correlation to identify features that allow for confirming or ruling out the intraplaque hemorrhage. MATERIALS AND METHODS: This retrospective study included 91 patients (67 men; median age, 657 years; age range, 41-83 years) who underwent CT angiography and carotid endarterectomy from March 2010 to May 2013. Histopathologic analysis was performed for the tissue characterization and identification of intraplaque hemorrhage. Two observers assessed the plaque's attenuation values by using an ROI (≤1 and ≥2 mm2). Receiver operating characteristic curve, Mann-Whitney, and Wilcoxon analyses were performed. RESULTS: A total of 169 slices were assessed (59 intraplaque hemorrhage, 63 lipid-rich necrotic core, and 47 fibrous); the average values of the intraplaque hemorrhage, lipid-rich necrotic core, and fibrous tissue were 17.475 Hounsfield units (HU) and 18.407 HU, 39.476 HU and 48.048 HU, and 91.66 HU and 93.128 HU, respectively, before and after the administration of contrast medium. The Mann-Whitney test showed a statistically significant difference of HU values both in basal and after the administration of contrast material phase. Receiver operating characteristic analysis showed a statistical association between intraplaque hemorrhage and low HU values, and a threshold of 25 HU demonstrated the presence of intraplaque hemorrhage with a sensitivity and specificity of 93.22% and 92.73%, respectively. The Wilcoxon test showed that the attenuation of the plaque before and after administration of contrast material is different (intraplaque hemorrhage, lipid-rich necrotic core, and fibrous tissue had P values of .006, .0001, and .018, respectively). CONCLUSIONS: The results of this preliminary study suggest that CT can be used to identify the presence of intraplaque hemorrhage according to the attenuation. A threshold of 25 HU in the volume acquired after the administration of contrast medium is associated with an optimal sensitivity and specificity. Special care should be given to the correct identification of the ROI

Thymosin Beta 4 may translocate from the cytoplasm in to the nucleus in HepG2 cells following serum starvation. An ultrastructural study

Due to its actin-sequestering properties, thymosin beta-4 (Tβ4) is considered to play a significant role in the cellular metabolism. Several physiological properties of Tβ4 have been reported;, however, many questions concerning its cellular function remain to be ascertained. To better understand the role of this small peptide we have analyzed by means of transmission immunoelectron microscopy techniques the ultrastructural localization of Tβ4 in HepG2 cells. Samples of HepG2 cells were fixed in a mixture of 3% formaldehyde and 0.1% glutaraldehyde in 0.1 M cacodylate buffer and processed for standard electron microscopic techniques. The samples were dehydrated in a cold graded methanol series and embedded in LR gold resin. Ultrathin sections were labeled with rabbit antibodies to Tβ4, followed by gold-labeled goat anti-rabbit, stained with uranyl acetate and bismuth subnitrate, observed and photographed in a JEOL 100S transmission electron microscope. High-resolution electron microscopy showed that Tβ4 was mainly restricted to the cytoplasm of HepG2 growing in complete medium. A strong Tβ4 reactivity was detected in the perinuclear region of the cytoplasmic compartment where gold particles appeared strictly associated to the nuclear membrane. In the nucleus specific Tβ4 labeling was observed in the nucleolus. The above electron microscopic results confirm and extend previous observations at light microscopic level, highlighting the subcellular distribution of Tβ4 in both cytoplasmic and nuclear compartments of HepG2 cells. The meaning of Tβ4 presence in the nucleolus is not on the best of our knowledge clarified yet. It could account for the interaction of Tβ4 with nucleolar actin and according with this hypothesis, Tβ4 could contribute together with the other nucleolar acting binding proteins to modulate the transcription activity of the RNA polymeras

Cellular trafficking of thymosin beta-4 in HEPG2 cells following serum starvation

Thymosin beta-4 (Tβ4) is an ubiquitous multi-functional regenerative peptide, related to many critical biological processes, with a dynamic and flexible conformation which may influence its functions and its subcellular distribution. For these reasons, the intracellular localization and trafficking of Tβ4 is still not completely defined and is still under investigation in in vivo as well as in vitro studies. In the current study we used HepG2 cells, a human hepatoma cell line; cells growing in normal conditions with fetal bovine serum expressed high levels of Tβ4, restricted to the cytoplasm until 72 h. At 84 h, a diffuse Tβ4 cytoplasmic immunostaining shifted to a focal perinuclear and nuclear reactivity. In the absence of serum, nuclear reactivity was localized in small granules, evenly dispersed throughout the entire nuclear envelop, and was observed as earlier as at 48 h. Cytoplasmic immunostaining for Tβ4 in HepG2 cells under starvation appeared significantly lower at 48 h and decreased progressively at 72 and at 84 h. At these time points, the decrease in cytoplasmic staining was associated with a progressive increase in nuclear reactivity, suggesting a possible translocation of the peptide from the cytoplasm to the nuclear membrane. The normal immunocytochemical pattern was restored when culture cells submitted to starvation for 84 h received a new complete medium for 48 h. Mass spectrometry analysis, performed on the nuclear and cytosolic fractions of HepG2 growing with and without serum, showed that Tβ4 was detectable only in the cytosolic and not in the intranuclear fraction. These data suggest that Tβ4 is able to translocate from different cytoplasmic domains to the nuclear membrane and back, based on different stress conditions within the cell. The punctuate pattern of nuclear Tβ4 immunostaining associated with Tβ4 absence in the nucleoplasm suggest that this peptide might be localized in the nuclear pores, where it could regulate the pore permeabilit

Modeling software design diversity

Design diversity has been used for many years now as a means of achieving a degree of fault tolerance in software-based systems. Whilst there is clear evidence that the approach can be expected to deliver some increase in reliability compared with a single version, there is not agreement about the extent of this. More importantly, it remains difficult to evaluate exactly how reliable a particular diverse fault-tolerant system is. This difficulty arises because assumptions of independence of failures between different versions have been shown not to be tenable: assessment of the actual level of dependence present is therefore needed, and this is hard. In this tutorial we survey the modelling issues here, with an emphasis upon the impact these have upon the problem of assessing the reliability of fault tolerant systems. The intended audience is one of designers, assessors and project managers with only a basic knowledge of probabilities, as well as reliability experts without detailed knowledge of software, who seek an introduction to the probabilistic issues in decisions about design diversity

IMP-3 expression in keratoacanthomas and squamous cell carcinomas of the skin: an immunohistochemical study

<p>The protein insulin-like growth factor II mRNA binding protein 3 (IMP3) is an important factor for cell migration and adhesion in malignancies. Recent studies have shown a remarkable overexpression of IMP3 in different human malignant neoplasms and also revealed it as an important prognostic marker in some tumor entities. The purpose of this study is to compare IMP3 immunostaining in squamous cellular skin tumor and determine whether IMP3 can aid in the differential diagnosis of these lesions. To our knowledge, IMP3 expression has not been investigated in skin squamous cell proliferations thus far. Immunohistochemical staining for IMP3 was performed on slides organized by samples from 67 patients, 34 with keratoacanthoma and 33 with primary squamous cell carcinoma (16 invasive and 17 <em>in</em><em> situ</em>). The majority of our KAs (25/34) were negative for IMP-3 staining. The majority of SCCs (19/33) are positive for IMP3 staining. The percentage of IMP3 positive cells increases significantly in group SCC (p=0.0111), and in particular in the SCC <em>in situ</em> group (p=0.0021) with respect to the KA group.  IMP3 intensity staining increases significantly in SCCs (p=0.0213), and particularly in SCCs (p=0.008) with respect to KA. Our data show that IMP3 expression is different in keratoacanthomas with respect to squamous cell carcinoma. IMP3 assessment and staining pattern, together with a careful histological study, can be useful in the differential diagnosis between KA e SCC.</p