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Achilles Heel (Achille + heel)
Selected AbstractsLack of desquamation , the Achilles heel of the reconstructed epidermisINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2002M. Ponec Synopsis The use of human skin equivalents for screening tests aiming to assess repetitive application of various test agents is hampered by the lack of desquamation in vitro. The present study was undertaken to examine whether the desquamation can be induced by various treatments including mechanical stress, application of various agents that should decrease the surface pH and calcium level, activate the enzymes involved in desquamation process or UV irradiation. In addition, the effect of ,-hydroxyacids, known to enhance desquamation and to improve the stratum corneum barrier function in vivo, was examined as well. Human epidermis reconstructed on de-epidermized dermis or on fibroblast-populated collagen matrices during a 2-week culture at the air,liquid interface underwent various treatments during an additional 3-week period. The effects of treatments were evaluated on the basis of tissue morphology and lipid composition. The results of the present study revealed that cell shedding could only be induced by a mild repetitive mechanical treatment. The lack of desquamation, under most in vitro conditions, has a practical consequence, since it may hamper the use of reconstructed epidermis for various screening studies aiming to examine the repetitive exposure to topical agents or UV irradiation. The gradual thickening of the stratum corneum will lead to its higher resistance to the environmental stimuli and in this way affect the outcome of the tests. Furthermore, from the results obtained in the present study, it became evident that one should be careful in selecting endpoints when, for example, the effects of agents known to modulate melanogenesis are examined. Résumé L'utilization d'équivalents cutanés humains dans les procédures de criblage, afin d'estimer l'action répétée de divers agents, est entravée par l'absence de desquamation in vitro. La présente étude a été entreprise afin de déterminer dans quelle mesure la desquamation peut être induite par différents traitements tels que stress mécanique, application d'agents divers qui conduiraient à une chute du pH de surface et du taux de Calcium, activeraient les enzymes impliquées dans le processus de desquamation, ou l'irradiation UV. De plus, l'effet des , hydroxy-acides, connus pour favouriser la desquamation et d'améliorer la fonction barrière du Stratum-Corneum in vivo, a étéétudié. L'épiderme humain reconstruit sur un derme dé-épidermisé ou sur des matrices de collagène colonisées par des fibroblastes pendant 2 semaines de culture, en interface air × liquide, a subi divers traitements pendant une période additionnelle de 3 semaines. Les effets de ces traitements étaient évalués sur des critères morphologiques du tissu ainsi que la composition en lipides. Les résultats de cette étude montrent que l'élimination cellulaire ne peut être induite que par un léger traitement mécanique répété. L'absence de desquamation dans la plupart des conditions in vitro a une conséquence pratique puisqu'elle peut entraver l'utilization de l'épiderme reconstruit à des fins diverses de criblage en vue d'appréhender les expositions répétées à des agents topiques, ou l'irradiation UV. L'épaississement progressif du Stratum-Corneum lui confèrera une résistance accrue aux stimuli environnementaux qui, en retour, modifiera les résultats des tests. De plus, les résultats de cette présente étude impliquent à l'évidence une précaution dans la sélection des cinétiques de mesures lorsque, par exemple, les effets des agents connus pour moduler la mélanogénèse sont étudiés. [source] Cell cycle checkpoints and their impact on anticancer therapeutic strategiesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2004Alan Eastman Abstract Cells contain numerous pathways designed to protect them from the genomic instability or toxicity that can result when their DNA is damaged. The p53 tumor suppressor is particularly important for regulating passage through G1 phase of the cell cycle, while other checkpoint regulators are important for arrest in S and G2 phase. Tumor cells often exhibit defects in these checkpoint proteins, which can lead to hypersensitivity; proteins in this class include ataxia,telangiectasia mutatated (ATM), Meiotic recanbination 11 (Mre11), Nijmegen breakage syndrome 1 (Nbs 1), breast cancer susceptibility genes 1 and 2 (BRCA1), and (BRCA2). Consequently, tumors should be assessed for these specific defects, and specific therapy prescribed that has high probability of inducing response. Tumors defective in p53 are frequently considered resistant to apoptosis, yet this defect also provides an opportunity for targeted therapy. When their DNA is damaged, p53-defective tumor cells preferentially arrest in S or G2 phase where they are susceptible to checkpoint inhibitors such as caffeine and UCN-01. These inhibitors preferentially abrogate cell cycle arrest in p53-defective cells, driving them through a lethal mitosis. Wild type p53 can prevent abrogation of arrest by elevating levels of p21waf1 and decreasing levels of cyclins A and B. During tumorigenesis, tumor cells frequently loose checkpoint controls and this facilitates the development of the tumor. However, these defects also represent an Achilles heel that can be targeted to improve current therapeutic strategies. © 2003 Wiley-Liss, Inc. [source] Civil Disobedience and Test CasesRATIO JURIS, Issue 3 2004María José Falcón y Tella The novelty of our focus resides in the priority given to the legal aspect of civil disobedience, especially to the possible legal justification of civil disobedience, a perspective that is generally overlooked in analysing the phenomenon. This is where the Achilles heel is to be found, though it may provide unexploited insights into the issue from which significant conclusions can be drawn. [source] WHAT HAS PSYCHOANALYSIS GOT TO DO WITH HAPPINESS?BRITISH JOURNAL OF PSYCHOTHERAPY, Issue 4 2009RECLAIMING THE POSITIVE IN PSYCHOANALYTIC PSYCHOTHERAPY abstract This paper questions whether what is a strength of psychoanalysis , its focus on painful and difficult experiences and its ability to remain in touch with the negative aspects of the personality , might also be an Achilles heel. The paper discusses research from neuroscience, developmental and social psychology to argue that more attention needs to be given to how we work with more positive and hopeful aspects of the personality, and that otherwise psychoanalytic psychotherapists are not working with the whole person. Some clinical examples are used to illustrate how these ideas might be used. [source] Internal loading: A new solution to an old problem in aquatic sciencesLAKES & RESERVOIRS: RESEARCH AND MANAGEMENT, Issue 1 2004Lars Håkanson Abstract Internal loading has long been regarded as an ,Achilles heel' in aquatic science and management. Internal loading is of fundamental importance in large and shallow lakes, where even low wind velocities can cause a considerable resuspension of matter deposited on the lake bed. The resuspended matter, and the chemical substances bound to the resuspended matter, will influence almost all processes in the aquatic ecosystem, such as water clarity and depth of the photic zone, and hence, primary and secondary production. If the sediments are contaminated, it will increase the concentrations of harmful substances in water and sediments and the potential ecosystem effects related to such concentrations. This paper presents an overview of the processes regulating bottom dynamic conditions in lakes (erosion, transport, accumulation), provides examples on the role of internal loading within the context of limnology and water management, and presents a new, general approach to quantify internal loading from sediments in lakes. The new approach has been critically tested, being a key factor behind the increase in predictive power of a new generation of lake models meant to be used for practical water management. Internal loading of any water pollutant depends on sedimentation. Sedimentation in this approach is presented as a function of two substance-specific variables, including the fall velocity of the carrier-particles and the particulate fraction (which, by definition, is the only fraction of a water pollutant that can settle out on the lake bed), and three generic variables, including mean depth, suspended particulate matter and ET-areas (areas of erosion and transport). On ET-areas there is, by definition, a discontinuous sedimentation of materials that settles according to Stokes' law. Basically, internal loading is the sum of advective (resuspension) and diffusive transport from the sediments. Resuspension from ET-areas is given as a function of the lake form (a new algorithm based on the volume development) and the age of ET-sediments. [source] Waiting for scheduled services in Canada: development of priority-setting scoring systemsJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 1 2003T. W. Noseworthy MD MSc MPH FRCPC FACP FCCP FCCM CHE Abstract Rationale, aims and objectives An Achilles' heel of Canadian Medicare is long waits for elective services. The Western Canada Waiting List (WCWL) project is a collaboration of 19 partner organizations committed to addressing this issue and influencing the way waiting lists are structured and managed. The focus of the WCWL project has been to develop and refine practical tools for prioritizing patients on scheduled waiting lists. Methods Scoring tools for priority setting were developed through extensive clinical input and highly iterative exchange by clinical panels constituted in five clinical areas: cataract surgery; general surgery procedures; hip and knee replacement; magnetic resonance imaging (MRI) scanning, and children's mental health. Several stages of empirical work were conducted to formulate and refine criteria and to assess and improve their reliability and validity. To assess the acceptability and usability of the priority-setting tools and to identify issues pertaining to implementation, key personnel in the seven regional health authorities (RHAs) participated in structured interviews. Public opinion focus groups were conducted in the seven western cities. Results Point-count scoring systems were constructed in each of the clinical areas. Participating clinicians confirmed that the tools offered face validity and that the scoring systems appeared practical for implementation and use in clinical settings. Reliability was strongest for the general surgery and hip and knee criteria, and weakest for the diagnostic MRI criteria. Public opinion focus groups endorsed wholeheartedly the application of point-count priority measures. Regional health authorities were generally supportive, though cautiously optimistic towards implementation. Conclusions While the WCWL project has not ,solved' the problem of waiting lists and times, having a standardized, reliable means of assigning priority for services is an important step towards improved management in Canada and elsewhere. [source] Performance-Based Regulation and Regulatory Regimes: The Saga of Leaky BuildingsLAW & POLICY, Issue 4 2003Peter J. May Regulatory reformers have widely endorsed greater use of a performance-based approach to regulation that defines objectives in terms of desired outcomes. The appeal of the performance-based approach is as much about introducing a regime that overcomes problems of overly rigid rules and inflexible enforcement as it is about regulating for results. The case of leaky buildings in New Zealand provides a cautionary tale of a flawed performance-based regulatory regime. It allowed for flexibility without sufficient accountability and in so doing showed the Achilles' heel of performance-based regulation. [source] A Neo-Boasian Conception of Cultural BoundariesAMERICAN ANTHROPOLOGIST, Issue 3 2004IRA BASHKOW For the past 30 years, anthropology's critics have repeatedly questioned the notion of "cultural boundaries," arguing that concepts of culture inappropriately posit stable and bounded "islands" of cultural distinctiveness in an ever-changing world of transnational cultural "flows." This issue remains an Achilles' heel,or at least a recurring inflamed tendon,of anthropology. However, in the conception of boundaries, we still have much to learn from Boasian anthropologists, who conceived of boundaries not as barriers to outside influence or to historical change, but as cultural distinctions that were irreducibly plural, perspectival, and permeable. In this article, I retheorize and extend the Boasians' open concept of cultural boundaries, emphasizing how people's own ideas of "the foreign",and the "own" versus the "other" distinction,give us a way out of the old conundrum in which the boundedness of culture, as conceived in spatial terms, seems to contradict the open-ended nature of cultural experience. [source] Untersuchung des Wärmeschutzes von Außenecken über unbeheizten Kellern in Wohngebäuden , die Achillesferse von massiven Außenwänden mit äußerer Wärmedämmung?BAUPHYSIK, Issue 4 2004Christoph Geyer Dr. rer. nat. Außenwände von Wohngebäuden werden häufig als massive Mauerwerkswände mit einer außenliegenden Wärmedämmung erstellt. Bei dieser Wandkonstruktion trennt aber der Mauerwerkssockel der massiven Außenwand im Erdgeschoß die Wärmedämmebene der Außenwand von der Wärmedämmebene der Kellerdecke über einem unbeheizten Keller. Hierdurch entsteht eine linienförmige Wärmebrücke. Die für den Mindestwärmeschutz kritischste Stelle tritt an der Außenecke im Erdgeschoß auf, wo sich je zwei dieser linienförmigen Wärmebrücken überlagern. Daher wird die minimale raumseitige Oberflächentemperatur an dieser Ecke für die Beurteilung des Mindestwärmeschutzes der Konstruktion herangezogen. Durch eine Vielzahl von dreidimensionalen Wärmebrückenberechnungen werden die Konstruktionseigenschaften der angrenzenden ebenen Bauteile herausgearbeitet, welche die minimale, raumseitige Oberflächentemperatur in der Außenecke über einem unbeheizten Keller und damit den Mindestwärmeschutz der Konstruktion beeinflussen. Es zeigt sich, daß eine minimale raumseitige Oberflächentemperatur in der Außenecke von 12, 6 °C erst mit Wärmedurchlaßwiderständen der Tragschale bzw. der gesamten Wandkonstruktion nachgewiesen werden kann, die wesentlich höher als 1, 2 m2K/W sind. Damit ist für diese Art von Außenwänden ein Mindestwärmeschutz nach Tabelle 3, DIN 4108-2 [1] mit einer Anforderung an den Wärmedurchlasswiderstand von R , 1,2 m2K/W nicht ausreichend, um den Mindestwärmeschutz auch für die Außenecke im Erdgeschoß rechnerisch nachweisen zu können. Es wird daher vorgeschlagen, ergänzende Hinweise in die Norm aufzunehmen. Examination of the thermal insulation characteristics of external corners above unheated basements in dwellings , the Achilles' heel of heavy-weight external walls with thermal insulation on the outside? External walls in dwellings consist often of a heavy-weight wall and a thermal insulation fixed outside. With this construction the insulation of the external wall is separated by the plinth of the external wall from the thermal insulation incorporated in the slab above an unheated basement. This results in a thermal bridge along the edge of the basement slab. The most critical point of the construction with regard to thermal protection occurs at the exterior corner at ground floor level, where two linear thermal bridges overlay. For this reason the minimum inner surface temperature of the corner is used to estimate the heat protection of the construction. A number of calculations of the minimum temperature at the interior surface of this three dimensional thermal bridge is performed to evaluate the parameters of the adjacent construction details which affect the minimum temperature at the inner surface of the corner. To reach the minimum temperature at he inner surface of the corner of 12.6 °C demanded by the German standard DIN 4108-2 as the minimum requirement of heat protection for thermal bridges, thermal resistances of the whole wall construction much higher than 1.2 m2K/W are necessary. For this construction type of exterior walls a thermal resistance of 1.2 m2K/W as demanded in table 3 of the German standard DIN 4108-2 as a minimum heat insulation for exterior walls can be shown to be insufficient to assure a minimum temperature of 12.6 °C at the inner surface of the corner at ground floor level. Thus it is proposed to add additional notes concerning this construction type in this standard. [source] | |||||||||||||