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Remote usability testing is performed by evaluators who are in different physical locations from the participants (synchronous remote testing) and possibly operating at different times (asynchronous remote testing). The tools developed in recent years to support remote tests exploit web technology based on HTML5 and JavaScript ES6 and thus enable previously unexplored scenarios. However, studies providing evidence on the benefits or drawbacks of utilizing recent web-based tools have not yet been reported in the literature. This article sheds some light on the impact of such tools on asynchronous remote usability testing of websites by reporting an experimental study with 100 participants and 15 evaluators to compare real-time laboratory tests with asynchronous remote tests. The study investigates: 1) how the metrics results of asynchronous remote usability tests performed through a web-based tool differ from those of usability tests conducted in real-time laboratory settings; and 2) how the experience of participants differs in the two types of tests. The lessons learned in the study are instrumental in informing the design of future tools. Some results of particular interest indicate that the web technology used by the tool for asynchronous remote testing affects task execution times and participants’ satisfaction. Another indication is that slow internet connections must be managed in asynchronous remote testing; slow connections introduce delays when transferring large amounts of collected data, which, together with the lack of human support, make participants of asynchronous remote tests more prone to feel negative emotions.

Occup Environ Med 2003;60:746-751 Aims: To study the concentration of N,N-dimethylacetamide (DMA) and its metabolite, N-methylacetamide (NMA), in urine of workers occupationally exposed to DMA in a factory producing synthetic [...]

In the era of precision medicine, liquid biopsy is becoming increasingly important in oncology. It consists in the isolation and analysis of tumor-derived biomarkers, including extracellular vesicles (EVs), in body fluids. EVs are lipid bilayer-enclosed particles, heterogeneous in size and molecular composition, released from both normal and neoplastic cells. In tumor context, EVs are valuable carriers of cancer information; in fact, their amount, phenotype and molecular cargo, including proteins, lipids, metabolites and nucleic acids, mirror nature and origin of parental cells rendering EVs appealing candidates as novel biomarkers. Translation of these new potential diagnostic tools into clinical practice could deeply revolutionize the cancer field mainly for solid tumors but for hematological neoplasms, too.

In the last few years, the rapid diffusion of components produced through additive manufacturing processes has boosted the research on design methodologies based on topology optimization algorithms. Structural topology optimization is largely employed since it permits to minimize the component weight and maximize its stiffness and, accordingly, optimize its resistance under structural loads. On the other hand, thermal topology optimization has been less investigated, even if in many applications, such as turbine blades, engines, heat exchangers, thermal loads have a crucial impact. Currently, structural and thermal optimizations are mainly considered separately, despite the fact that they are both present and coupled in components in service condition. In the present paper, a novel methodology capable of defining the optimized structure under simultaneous thermomechanical constraints is proposed. The mathematical formulation behind the optimization algorithm is reported. The proposed methodology is finally validated on literature benchmarks and on a real component, confirming that it permits to define the topology, which presents the maximized thermal and mechanical performance.

Additive manufacturing for fibre-reinforced composite structures is rapidly diffusing, since it enables the production of lightweight structural parts characterized by complex geometries and tailored fibre orientations. Therefore, the development of design methodologies capable to simultaneously optimize the shape of the fibre-reinforced composite part and the fibre orientation in the additive manufacturing process is, at present, of utmost interest among industries and research centres. In this paper, a novel simultaneous optimisation method capable to optimise the topology and the local fibre orientation is proposed. The method is computationally cheap, fast convergent and permits to avoid stress peaks, working efficiently on 2D and on 3D models. The analytical formulation of the problem and the optimisation algorithm are at first described. The optimisation criteria are based on the uniform strain energy density distribution and the fibre alignement along the principal stress direction. The proposed method is then verified with several benchmarks from the literature and with a 3D illustrative example, confirming that it can be effectively and efficiently employed for the optimisation of composite components to be produced through additive manufacturing.

A 6-mo-old female Beagle dog was inappetent and depressed. The radiographic, ultrasonographic, and computed tomographic examination of the chest revealed a 10 × 7 cm multicystic mediastinal structure interpreted as altered thymus, in association with moderate pleural effusion that laboratory tests confirmed as hemothorax. No history of trauma or anticoagulant drug intoxication was reported, and no coagulation disorders were detected. Afterward, medial cranial sternotomy was performed to remove the altered tissue. Histologically, this tissue was compatible with a thymic remnant, characterized by numerous cystic lesions, mostly blood filled and lined by flattened-to-cuboidal epithelial cells, occasionally projecting into the surrounding stroma, and forming cytokeratin-positive ribbons, trabeculae, and papillae. Lymphocytes were scant, and numerous areas of congestion and hemorrhage were present throughout the samples. This case of idiopathic thymic hemorrhage with cystic degeneration of the thymus and pseudoepitheliomatous hyperplasia was an incidental finding; the dog recovered from surgery uneventfully.

ABSTRACTNasal drug delivery has specific challenges which are distinct from oral inhalation, alongside which it is often considered. The next generation of nasal products will be required to deliver new classes of molecule, e.g. vaccines, biologics and drugs with action in the brain or sinuses, to local and systemic therapeutic targets. Innovations and new tools/knowledge are required to design products to deliver these therapeutic agents to the right target at the right time in the right patients. We report the outcomes of an expert meeting convened to consider gaps in knowledge and unmet research needs in terms of (i) formulation and devices, (ii) meaningful product characterization and modeling, (iii) opportunities to modify absorption and clearance. Important research questions were identified in the areas of device and formulation innovation, critical quality attributes for different nasal products, development of nasal casts for drug deposition studies, improved experimental models, the use of simulations and nasal delivery in special populations. We offer these questions as a stimulus to research and suggest that they might be addressed most effectively by collaborative research endeavors.

The sustainable development goals (SDGs) present a real opportunity to direct India towards a path of equality and equity. This article posits that India’s plans to achieve the millennium development goals by the end of their term in 2015 faltered because reforms designed to alleviate poverty and achieve equitable growth did not adequately address weaknesses in institutions of accountability, which undermined the reform agenda. These institutions, which include Parliament and the judiciary, exist in part to ensure that actions taken by public officials are subject to oversight so that government initiatives meet their stated objectives. As India shifts its attention to Agenda 2030, its renewed commitment to institutional reforms represents an occasion for the state to address the inequalities in income and the resulting human development concerns. For the government to achieve the SDGs, this article suggests that India must integrate what we refer to as a baseline conception of distributive justice within its plans, which can account for structural barriers to its development arising from ineffective institutions of accountability and provide the poor with a route towards individual empowerment.

A 10-month-old male American Pitbull Terrier puppy was treated for the correction of cor triatriatum dexter by balloon catheter dilation under echocardiographic guidance. Two weeks after the interventional procedure, the dog presented ascites because re-stenosis of cor triatriatum dexter occurred. A second interventional procedure, by combining membranostomy and balloon catheter dilation of the intra-atrial septum, allowed the resolution of congestive heart failure. Based on the clinical outcome, the alternative approach described in this report appears to be a viable treatment option for dogs affected with cor triatriatum dexter, especially when re-stenosis occurs.

Migrating plant material is often suspected clinically to be the underlying cause of iliopsoas myositis in the dog, but cannot always be found pre- or intraoperatively. In most cases, recurrence of clinical signs is related to failure to remove the plant material. Preoperative ultrasonography can be useful to visualize migrating plant material and to determine anatomical landmarks that can assist in planning a surgical approach. The purpose of the present study was to report the role of intraoperative (intra-abdominal) ultrasonography for visualizing and removing the plant material from iliopsoas abscesses using a ventral midline laparotomy approach. A retrospective case series of 22 dogs with iliopsoas muscle abnormalities and suspected plant material was reported. Preoperative visualization and subsequent retrieval of the plant material was performed during a single hospitalization. In all 22 dogs, the plant material (including complete grass awns, grass awn fragments and a bramble twig) was successfully removed via ventral midline laparotomy in which intraoperative ultrasonography was used to direct the grasping forceps tips to the foreign body and guide its removal. In 11 of these 22 dogs, the plant material was not completely removed during prior surgery performed by the referring veterinarians without pre- or intraoperative ultrasonography. Clinical signs resolved in all dogs and all dogs resumed normal activity after successful surgical removal of the plant material. Intraoperative ultrasonography is a safe and readily available tool that improves success of surgical removal of plant material within the iliopsoas abscesses via ventral midline laparotomy. Moreover, ultrasonographic findings of unusual plant material can be useful in planning and guiding surgical removal, by providing information about the size and shape of the foreign body.

A new report, 'Women on the Verge: Corporate Power in Latin America, tells an amazing success story, one that would have been unthinkable just 10 years ago. Surveys conducted by [...]

Purpose The growing incidence of renal cell carcinoma (RCC) raises many questions about the management of these patients. The late clinical presentation, the presence of locally advanced or metastatic disease at diagnosis, the difficulty of radical surgical excision, and radioresistance make it one of the more challenging tumors to treat. The primary objective of this article is to propose an updated and critical review of the role of radiotherapy (RT) in the treatment of RCC.Methods This literature review is based on data from meta-analyses and randomized, prospective, and retrospective studies. We collected reports from 1970 to the present about preoperative RT, postoperative RT, stereotactic body RT, radiosurgery, and intraoperative RT in locally advanced renal cancer and in metastatic diseases.Results We emphasize the progress made in RT technology that allowed the creation of a more personalized and focused treatment with a minimum rate of complications.Conclusions In the coming years, new studies will be published to confirm and increase the indications for use of RT.

Background.Dead code is a code smell. It can refer to code blocks, fields, methods, etc. that are unused and/or unreachable—e.g., if a method is unused and/or unreachable, it is a dead method. Past research has shown that the presence of dead code in source code harms its comprehensibility and maintainability. Nevertheless, there is still little empirical evidence on the spread of this code smell in the source code of commercial and open-source software applications.

IntroductionCatheter-ablation (CA) is routinely used for the treatment of atrio-ventricular nodal re-entrant tachycardia (AVNRT) and accessory AV-pathways and is usually performed with 4 or 5 catheters.This study reports the short- and long-term results of an alternative simplified approach with a 2-catheter configuration for both electrophysiological study (EPS) and CA in patients with re-entrant supraventricular tachycardias.MethodsIn total, 274 consecutive patients who underwent EPS with a view to curative CA for AVNRT or AVRT were enrolled. A 2-catheter configuration was routinely used. Ablation success, acute in-hospital complications, symptoms recurrence, arrhythmia recurrence were recorded.Results195 patients underwent ablation of AVNRT and 79 of a single AP. Immediate success after CA ablation was achieved in 99.6% of patients. Major complications occurred in 2 patients (0.73%, 2 cases of complete AV block, one of which requiring pacemaker implantation after 1 year, one during typical AVNRT ablation and one during epicardial AP-ablation).Vascular complications occurred in 4 patients (1.4%, 3 partial femoral vein thrombosis without embolic events, one femoral arteriovenous fistula). Minimal pericardial effusion occurred in 6 patients (2.2%). All vascular complications were medically successfully treated not requiring surgery.The mean follow-up was 86 months. Arrhythmia recurrence was observed in 5.6% of patients (2.6% with AP, 2.9% with AVNRT); a second successful catheter ablation was performed in 2.9%.ConclusionsCA with simplified approach is effective in the treatment of supraventricular tachycardia due to APs and AVNRT and is associated with a low incidence of major and minor complications and late recurrence of arrhythmias.

The past decade has witnessed a revival in interest in the relationship between rule of law and economic development. Disenchantment with the universal model that emerged from the Washington Consensus era led to a shift in focus to a more pluralist approach in which policy prescriptions became tailored to each country’s socio-political context. The authors suggest that the pendulum may have swung to the other extreme, and that the newly ascendant pluralist approach may overemphasize pluralism at the expense of core rule of law principles. This paper examines the rule of law building efforts pursued by the BRIC countries to shed light on their strikingly different processes of economic transition. The authors argue that formal, informal, and transitional institutions have played distinct roles in these divergent economic development narratives. While informal and transitional institutions have facilitated growth during initial and intermediate phases of development, a degree of formalization across some institutions is critical to support the long-term development of a market economy. The authors set out the core tenets approach, an exploratory concept that emphasizes a malleable set of fundamental rule of law principles which exist alongside transition institutions to build trust in formal institutions as an economy advances.

The purpose of this study was to understand youth's attitudes and emotions towards responses to cybergossip. Youth (N = 160, ages 10–16) read ten stories involving cybergossip, where an individual received gossip electronically from a friend. The target of gossip was either another friend or a classmate (Target Relationship: friend/classmate). The gossip receiver responded to the gossip sharer in five different ways (Response: passive/positive intervention/negative intervention/encouraging/blocking). In addition, as a between-subjects factor, the online setting was either a private conversation between the sharer and receiver or a public setting involving the sharer, receiver, and a few other friends in a group chat (Setting: private/public). Age (preadolescent/adolescent) and gender (female/male) differences were also examined. Participants were asked to morally evaluate each response, rate the effectiveness of each response, and rate their emotions towards using each response. The findings highlight the nuances of responding to cybergossip and the role of personal and contextual factors. Moreover, the results suggest there are misconceptions among youth about the effectiveness of interventions. These results and others as well as the implications will be discussed. The findings provide critical information on what youth in today's digital world believe are acceptable and effective ways to cyber-communicate.

We describe observation driven time series models for Student-t and EGB2 conditional distributions in which the signal is a linear function of past values of the score of the conditional distribution. These specifications produce models that are easy to implement and deal with outliers by what amounts to a soft form of trimming in the case of t and a soft form of Winsorizing in the case of EGB2. We show how a model with trend and seasonal components can be used as the basis for a seasonal adjustment procedure. The methods are illustrated with US and Spanish data.

Aims To evaluate the utility of a multiparametric 3T magnetic resonance imaging (MRI) study using diffusion-weighted images (DWI) for the assessment of prostate cancer before and after radiotherapy (RT).Methods A total of 34 patients, who received a histologic diagnosis of prostate adenocarcinoma, underwent MRI examination before and after local RT for the assessment of response to treatment. Apparent diffusion coefficient (ADC) values were calculated and compared.Results Before RT, DWI shows pathologic restriction of signal, while after RT pathologic restriction of signal was reduced or disappeared. The ADC values were significantly increased after therapy (p<0.05).Conclusions The use of DWI with ADC measurements may be an imaging biomarker in the assessment of prostate cancer.

A three-month-old female Rottweiler puppy was referred for intravascular correction of a previously identified cor triatriatum dexter. Echocardiography confirmed the presence of a hyperechoic membrane that divided the right atrium into a cranial and caudal chamber. A foramen in this membrane allowed the blood to flow from the caudal to the cranial chamber. Balloon dilation of the defect under transthoracic echocardiographic guidance was scheduled for the following day. The dog was premedicated with 0.5 μg/kg sufentanil and 0.2 mg/kg midazolam administered intravenously. General anaesthesia was induced with 2 mg/kg propofol and maintained with inhaled isoflurane in oxygen; at the same time, a constant rate infusion of 0.5 μg/kg/h sufentanil was administered by means of an infusion pump. Uneventful ventricular and supraventricular tachyarrhythmias developed during the placement of catheters and balloon dilation. At the end of procedure, when the guide wire and balloon catheter were removed, normal sinus rhythm was observed. To the authors’ knowledge, no previous reports have described the anaesthetic management of a balloon dilation procedure for cor triatriatum dexter in dogs.

Semiosis, and particularly visual semiosis, is not something unique to humans. All animal species, all living beings (including other forms of life outside the animal kingdom) have semiotic activity. But we can go even beyond that. It is possible to maintain that also in the world that is usually called “inanimate” or “inert” some kind of semiotic activity takes place. This paper proposes a view in which the elements and organisms in the natural environment, instead of being classified into separate categories are thought of as forming a continuous gradation from one to another, from lower to upper levels of complexity and semiotic behavior. From this, and from further arguments, it is possible to maintain that semiosis permeates the entire universe. A special point is made concerning the interaction of light stimuli with matter and living organisms, which in some cases has produced the systems of vision that many animals posses, and in some other cases produce reactions and changes that can be considered as a kind of protosemiotic activity.

As a certified professional in health and fitness, I am constantly seeking new avenues to expand my capabilities and diversify my experience. In so doing, I frequently delve into industry [...]

In silicotarget fishing is an emerging tool in drug discovery, which is mostly used for primary target or off-target prediction and drug repositioning. In this work, we developed an in silicotarget fishing protocol to identify the primary target of GV2–20, a false-positive hit highlighted in a cell-based screen for 14–3–3 modulators. Although GV2–20 does not bind to 14–3–3 proteins, it showed remarkable antiproliferative effects in CML cells, thus raising interest toward the identification of its primary target. Six potential targets of GV2–20 were prioritized in silicoand tested in vitro. Our results show that the molecule is a potent inhibitor of carbonic anhydrase 2 (CA2), thus confirming the predictive capability of our protocol. Most notably, GV2–20 experienced a remarkable selectivity for CA2, CA7, CA9, and CA12, and its scaffold was never explored before as a chemotype for CA inhibition, thus becoming an interesting lead candidate for further development.

Aims and background To present the Italian state-of-the-art contribution to radiobiology of external beam radiotherapy, brachytherapy, and radionuclide radiotherapy.Methods and study design A survey of the literature was carried out, using PubMed, by some independent researchers of the Italian group of radiobiology. Each paper was reviewed by researchers of centers not comprising its authors. The survey was limited to papers in English published over the last 20 years, written by Italian investigators or in Italian institutions, excluding review articles.Results A total of 135 papers have been published in journals with an impact factor, with an increase in the number of published papers over time, for external beam radiotherapy rather than radionuclide radiotherapy. The quantity and quality of the papers researched constitutes a proof of the enduring interest in clinical radiobiology among Italian investigators.Conclusions The survey could be useful to individuate expert partners for an Italian network on clinical radiobiology, addressing future collaborative investigations.

Due to the anatomical changes frequently occurring during the course of head and neck (H&N) cancer radiotherapy, the dose distribution, which was actually delivered to the patient, might significantly differ from that planned. The aim of this paper is to investigate these volumetric changes and the resulting dosimetric implications on organs at risk (OARs) and clinical target volumes (CTVs) by cone beam computed tomography (CBCT) scans throughout the treatment. Ten H&N patients, treated by Intensity Modulated Radiotherapy, were analyzed. CTVs and OARs were delineated on four CBCT, acquired at the 10th, 15th, 20thand 25thtreatment session, and then compared with the ones at planning CT. The planned beams were applied to each CBCT to recalculate the dose distribution and the corresponding dose volume histograms were compared with those generated on planning CT. To evaluate the HU discrepancies between the conventional CT and CBCT images we used a Catphan® 504, observing a maximum discrepancy of about 30 HU. We evaluated the impact of this HU difference in dose calculation and a not clinically relevant error, within 2.8%, was estimated. No inhomogeneity correction was used. The results showed an increased CTV mean dose (Dmean) of about 3% was found, without significant reduction in volume. Due to the parotids' shrinkage (up to 42%), significant dosimetric increases were observed: ipsilateral gland at 15thCBCT (Dmeanby 18%; V30 by 31%); controlateral gland at the 10thCBCT (Dmeanby 12.2%; V30 by 18.7%). For the larynx, a significant increase of volume was found at the 20th(15.7%) and 25thCBCT (13.3%) but it complied with dose constraint. The differences observed for the spinal cord and mandible maximum doses were not clinically relevant. In conclusion, the dosimetric analysis on CBCT can help clinicians to monitor treatment progress and to evaluate whether and when a new plan is necessary. The main benefit of replanning could be to preserve the parotids and our data support the hypothesis that the 3rdweek of radiotherapy should be a check point for parotids.

Prevention is the best treatment for cerebrovascular disease, which is why early diagnosis and the immediate treatment of carotid stenosis contribute significantly to reducing the incidence of stroke. Given its silent nature, 80% of stroke cases occur in asymptomatic individuals, emphasizing the importance of screening individuals with carotid stenosis and identifying high-risk groups for the disease. The aim of this study was to determine the prevalence and the most frequent risk factors for carotid stenosis.

A personal narrative is presented that describes how the author designed the home of John Ed and Isabel Anthony in Mount Desert Island, Maine, that blends with its environment.

The authors describe the use of modified baculoviruses containing mammalian expression cassettes (BacMam technology) in steroid nuclear receptor reporter assays designed for screening and profiling agonist and antagonist compounds. Baculo-viruses were constructed that express full-length human genes for mineralocorticoid receptor (MR), glucocorticoid receptor (GR), progesterone receptor A (PR-A), and progesterone receptor B (PR-B) from the cytomegalovirus immediate early promoter. A virus carrying the mouse mammary tumor virus–firefly luciferase (MMTV-Luc) cassette was generated to provide a suitable reporter construct. Feasibility studies with BacMam-MR in single-dose tests of 1000 compounds showed high correlation to the standard transfection-based assay results. Likewise, in dose-response experiments, BacMam-based assays for GR and PR-B produced potency and efficacy values similar to transfection assay results. At various receptor/reporter ratios, the BacMam assays showed good flexibility, demonstrating consistent signal-to-background (S/B) ratios and compound potencies. Increasing transduction time from 24 to 48 h provided no benefit, actually reducing overall assay performance as measured by S/B and Z′ values. The BacMam technology was applied in studies of isoforms PR-A and PR-B, which showed similar responses to a series of agonists. Taken together, the results demonstrate the utility of steroid nuclear receptor BacMam constructs for compound screening procedures with high reproducibility, reduced turnaround time, and lower cost.

Two non-pathogenic scaffolds (represented by the filamentous bacteriophage fd and the dihydrolipoyl acetyltransferase E2 protein of the Bacillus stearothermophilus pyruvate dehydrogenase (PDH) complex) able to deliver human immunodeficiency virus (HIV)-1 antigenic determinants, were designed in our laboratories and investigated in controlled assay conditions. Based on a modification of the phage display technology, we developed an innovative concept for a safe and inexpensive vaccine in which conserved antigenic determinants of HIV-1 reverse transcriptase (RTase) were inserted into the N-terminal region of the major pVIII coat protein of bacteriophage fd virions. Analogously, we developed another antigen delivery system based on the E2 component from the PDH complex and capable of displaying large intact proteins on the surface of an icosahedral lattice. Our data show that both of these systems can deliver B and T epitopes to their respective presentation compartments in target cells and trigger a humoral response as well as a potent helper and cytolytic response in vitro and in vivo.

Prostaglandins are important mediators of activated macrophage functions, and their inducible synthesis is mediated by cyclooxygenase-2 (COX-2). Here, we make use of the murine macrophage cells RAW264 as well as of immortalized macrophages derived from mice deficient for the transcription factor CCAAT enhancer-binding protein β (C/EBPβ) to explore the molecular mechanisms regulating COX-2 induction in activated macrophages. We demonstrate that lipopolysaccharide-mediated COX-2 mRNA induction is biphasic. The initial phase is independent of de novoprotein synthesis, correlates with cAMP-response element-binding protein (CREB) activation, is inhibited by treatments that abolish CREB phosphorylation and reduce NF-κB-mediated gene activation, and requires the presence of the transcription factor C/EBPβ. On the other hand, C/EBPδ appears to be essential in addition to C/EBPβ to effect the second phase of COX-2 gene transcription, which is important for maintaining the induced state and requires de novoprotein synthesis. Indeed, both phases of COX-2 induction were defective in C/EBPβ−/− macrophages. Moreover, the synthesis of C/EBPδ was increased dramatically by treatment with lipopolysaccharide and, like COX-2 induction, repressed by combined inhibition of the MAPK and of the SAPK2/p38 cascades. Taken together, these data identify CREB, NF-κB, and both C/EBPβ and -δ as key factors in coordinately orchestrating transcription from the COX-2 promoter in activated macrophages.

Cyclooxygenase-2 (COX-2) is the rate-limiting enzyme for the inducible synthesis of prostaglandins, and its up-regulated activity is thought to play a pathological role in diseases such as inflammatory bowel disease, rheumatoid arthritis, and cancer. Regulation of COX-2 expression is complex and appears to involve diversified mechanisms in different cell types and conditions. Here we make use of immortalized macrophages and fibroblasts that we have generated from C/EBPβ-deficient mice to directly test and compare the specific role played by this factor in inducible COX-2 expression in these two cell types. We could demonstrate that COX-2 mRNA induction and promoter activity were profoundly impaired in C/EBPβ−/−macrophages and could be rescued by expression of C/EBPβ. The obligatory role of C/EBPβ in COX-2 expression appeared to be mediated exclusively by the C/EBP element located at positions −138/−130 of the murinecox-2promoter, and did not involve altered activity at the level of the other promoter elements described previously (the −402/−392 NF-κB site, the −59/−48 CRE/E box element, and a potential second C/EBP site located at positions −93/−85). In contrast, COX-2 induction was completely normal in C/EBPβ-deficient fibroblasts, thus highlighting the diversity of cell-specific molecular mechanisms in determining inducible COX-2 expression and prostaglandins production.

The specificities of 28 commercially available compounds reported to be relatively selective inhibitors of particular serine/threonine-specific protein kinases have been examined against a large panel of protein kinases. The compounds KT 5720, Rottlerin and quercetin were found to inhibit many protein kinases, sometimes much more potently than their presumed targets, and conclusions drawn from their use in cell-based experiments are likely to be erroneous. Ro 318220 and related bisindoylmaleimides, as well as H89, HA1077 and Y 27632, were more selective inhibitors, but still inhibited two or more protein kinases with similar potency. LY 294002 was found to inhibit casein kinase-2 with similar potency to phosphoinositide (phosphatidylinositol) 3-kinase. The compounds with the most impressive selectivity profiles were KN62, PD 98059, U0126, PD 184352, rapamycin, wortmannin, SB 203580 and SB 202190. U0126 and PD 184352, like PD 98059, were found to block the mitogen-activated protein kinase (MAPK) cascade in cell-based assays by preventing the activation of MAPK kinase (MKK1), and not by inhibiting MKK1 activity directly. Apart from rapamycin and PD 184352, even the most selective inhibitors affected at least one additional protein kinase. Our results demonstrate that the specificities of protein kinase inhibitors cannot be assessed simply by studying their effect on kinases that are closely related in primary structure. We propose guidelines for the use of protein kinase inhibitors in cell-based assays.

The aim of this article is twofold: to make semioticians interested in visual semiotics better acquainted with the very elaborate aspects of color theory, from which they could take models to develop other aspects of visual semiotics, and to make color theorists more familiar with general semiotics, a paradigm that can encompass and organize the whole study of color. General semiotic notions are described and illustrated with examples taken from the domain of color, and an account of some of the advances of color theory is given within the framework of semiotic categories. Aspects such as color semantics, color grammar, color harmony, color combinations, and others, are reviewed. © 1998 John Wiley & Sons, Inc. Col Res Appl, 23: 390–401, 1998

Many artists and scientists have been concerned, throughout time, with the correspondences between color and sound. Numerous studies on the subject have been written. There are approaches based on intuition as well as approaches based on psychology, psychophysics, physics, and physiology The classical comparison relies on the fact that the stimuli for the sensations of pitch in sound and hue in color are mainly determined by the wavelength of the auditory energy and the visible energy. both taken as undulatory phenomena. On this basis. a comparison is usually drawn between the chromatic scale of sounds and the hue circle. This criterion has been followed to such extent to relate a sound of specific frequency with a determined spectral color. The comparison can be expanded and refined by considering the other variables of sound and color. too. This article relates luminosity of color with loudness of sound. saturation of color with timbre of sound, and size of color with duration of sound. There are psychological and physical arguments to support such a comparison. © 1994 John Wiley & Sons, Inc.

Presenilin 1 (PS–1) has been identified as the protein encoded by the chromosome 14 locus that, when mutated, leads to familial Alzheimer's disease (FAD). Using PS–1 transfected SHSY5Y neuroblastoma cells, we have demonstrated by immunodetection, using polyclonal antibodies, that PS–1 is processed to give two fragments: an N–terminal 28 kDa fragment, and a C–terminal 18 kDa fragment. In a number of non-transfected cell types, most PS–1 is detected as the cleaved products. The molecular weights of the PS–1 cleavage products suggest that the cleavage point will most probably be within a region of the hydrophilic loop domain coded for by either exon 8 or 9 of the PS–1 gene. The clustering of FAD mutations within exon 8 strongly suggests that it encodes a key functional domain. It seems likely that the cleavage of PS–1 is crucial to some aspect of its functionality. An understanding of this process will give insights into the pathology of AD, and may offer new opportunities for therapeutic intervention.

Ewing tumor is the second most common bone tumor in children. Its variant, malignant small cell tumor of the thoracopulmonary region, is infrequent in children and extremely rare in adults. A multimodal treatment approach is preferred for this tumor. We describe a rare case of primitive neuroectodermal tumor/Ewing sarcoma arising from the thoracic wall in a 54-year-old man. He underwent extensive resection of the tumor followed by adjuvant chemotherapy and radiotherapy.

Several letters to the editor are presented in response to articles in previous issues including an article by Thomas J. Norton on anamorphic lenses in the October 2008 issue, a review of the Pioneer Elite KURO PRO-111FD plasma high definition television (HDTV), and Fred Manteghian's review of the Rotel RSP-1069 surround processor in the October 2008 issue.

We report the case of a patient undergoing two surgeries in the right and left occipital lobes for resection of primary central nervous system tumor at different times. The first approach was performed in the left hemisphere, with the patient awake and, five months later, the second approach was performed in the right hemisphere, with the use of VEP for the study of the visual pathways. Both procedures were performed by the same surgical team, anesthesiologist and intraoperative monitoring neurophysiologist. Nevertheless, the outcomes were different, and the patient evolved with a left inferior temporal quadrantanopia after the second surgery, a deficit not detected by VEP.