985 resultados para epistemic closure
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Actin-based motor protein requirements and nitric oxide (NO) production are important features of macrophage activity during phagocytosis or microbicidal processes. Different classes of myosins contribute directly or indirectly to phagocytosis by providing mechanical force for phagosome closure or organelle movement. Recent data have shown the presence of myosins IC, II, V and IXb in phagosomes of bone marrow-derived murine macrophages. In our investigation we demonstrated the presence of different classes of myosins in J774 macrophages. We also analyzed the effect of gamma interferon (IFN-gamma), with or without calcium ionophore or cytochalasin B, on myosins as well as on inducible nitric oxide synthase (iNOS) expression and NO production. Myosins IC, II, Va, VI and IXb were identified in J774 macrophages. There was an increase of myosin V expression in IFN-gamma-treated cells. iNOS expression was increased by IFN-gamma treatment, while calcium ionophore and cytochalasin B had a negative influence on both myosin and iNOS expression, which was decreased. The increases in NO synthesis were reflected by increased iNOS expression. Macrophages activated by IFN-gamma released significant amounts of NO when compared to control groups. In contrast, NO production by calcium ionophore- and cytochalasin B-treated cells was similar to that of control cells. These results suggest that IFN-gamma is involved in macrophage activation by stimulating protein production to permit both phagocytosis and microbicidal activity.
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Current immunological opinion disdains the necessity to define global interconnections between lymphocytes and regards natural autoantibodies and autoreactive T cells as intrinsically pathogenic. Immunological theories address the recognition of foreignness by independent clones of lymphocytes, not the relations among lymphocytes or between lymphocytes and the organism. However, although extremely variable in cellular/molecular composition, the immune system preserves as invariant a set of essential relations among its components and constantly enacts contacts with the organism of which it is a component. These invariant relations are reflected, for example, in the life-long stability of profiles of reactivity of immunoglobulins formed by normal organisms (natural antibodies). Oral contacts with dietary proteins and the intestinal microbiota also result in steady states that lack the progressive quality of secondary-type reactivity. Autoreactivity (natural autoantibody and autoreactive T cell formation) is also stable and lacks the progressive quality of clonal expansion. Specific immune responses, currently regarded as the fundament of the operation of the immune system, may actually result from transient interruptions in this stable connectivity among lymphocytes. More permanent deficits in interconnectivity result in oligoclonal expansions of T lymphocytes, as seen in Omenn's syndrome and in the experimental transplantation of a suboptimal diversity of syngeneic T cells to immunodeficient hosts, which also have pathogenic consequences. Contrary to theories that forbid autoreactivity as potentially pathogenic, the physiology of the immune system is conservative and autoreactive. Pathology derives from failures of these conservative mechanisms.
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The desire to create a statistical or mathematical model, which would allow predicting the future changes in stock prices, was born many years ago. Economists and mathematicians are trying to solve this task by applying statistical analysis and physical laws, but there are still no satisfactory results. The main reason for this is that a stock exchange is a non-stationary, unstable and complex system, which is influenced by many factors. In this thesis the New York Stock Exchange was considered as the system to be explored. A topological analysis, basic statistical tools and singular value decomposition were conducted for understanding the behavior of the market. Two methods for normalization of initial daily closure prices by Dow Jones and S&P500 were introduced and applied for further analysis. As a result, some unexpected features were identified, such as a shape of distribution of correlation matrix, a bulk of which is shifted to the right hand side with respect to zero. Also non-ergodicity of NYSE was confirmed graphically. It was shown, that singular vectors differ from each other by a constant factor. There are for certain results no clear conclusions from this work, but it creates a good basis for the further analysis of market topology.
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Tässä diplomityössä on tutkittu lauhdekapasiteetin ennenaikaisen markkinoilta poistumisen energiataloudellisia vaikutuksia. Tarkastelu toteutettiin sähkömarkkinamallinnuksen avulla luomalla kaksi erilaista lauhdekapasiteettiskenaariota perustuen arvioituun lauhdekapasiteetin poistumiseen sekä vastavuoroisesti sen säilymiseen markkinoilla. Skenaarioiden vaikutuksia tutkittiin myös herkkyystarkasteluin ja tuloksia analysoitiin energiataloudellisesta näkökulmasta. Työn tavoitteena oli selvittää lauhdekapasiteetin ennenaikaisen poistumisen energiataloudellista kustannusta. Viime vuosien pitkittynyt talouden taantuma on hillinnyt kysynnän ennakoitua kehitystä johtaen alhaiseen sähkön markkinahintatasoon. Samalla tiukentuneet energiatuotannon ympäristövaatimukset asettavat investointirasitteita perinteisille voimalaitoksille heikentäen niiden taloudellisen kannattavuuden edellytyksiä. Markkinasähkön alhainen hintataso yhdessä investointirasitteiden kanssa asettaa haasteita etenkin usein rajatuotantomuotona toimiville lauhdelaitoksille. Alhaisen kannattavuuden seurauksena lauhdekapasiteettia arvioidaan poistuvan ennen teknisen käyttöiän täyttymistä markkinoilta merkittävästi lähivuosina. Kapasiteetin poistuminen kasvattaa oman tuotannon ja kysynnän välistä tehovajetta, minkä vuoksi sähköjärjestelmän nähdään tiukentuvan merkittävästi ennen rakenteilla olevan ydinvoimalaitoksen valmistumista. Työssä toteutettujen mallinnusten perusteella lauhdekapasiteetin väheneminen nostaa sähkön hintatasoa sekä lisää korkeiden hintapiikkien esiintymistä merkittävästi suhteessa korkeamman kapasiteetin tuloksiin. Sähköjärjestelmä on hyvin tiukka ennen rakenteilla olevan ydinvoimalaitoksen käyttöönottoa, minkä vuoksi lauhdekapasiteetin eroavaisuuksien vaikutukset ovat merkittävä etenkin poikkeuksellisen kylmänä vuotena. Lauhdekapasiteetin merkitys pienenee selvästi 2020-luvulla, kun oma tuotantokapasiteetti kasvaa. Työn tulosten perusteella lähivuosina alhaisemman lauhdekapasiteetin aiheuttama vuotuinen energiataloudellinen kustannus on huomattavasti korkeampi kuin laitosten kannattavan ylläpidon vaatima kustannus.
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Suomen metsäteollisuus elää voimakasta uusiutumis- ja murrosvaihetta, joka ilmenee muutoksina yksittäisten tehtaiden ja tehdasintegraattien toiminnassa. Monia yksikköjä on poistunut tuotannosta ja tuotannon painotusta on muutettu. Toisaalta metsäteollisuus on suuntaamassa uusille aloille, jolloin tuotteina voivat olla esimerkiksi erilaiset biopolttoaineet, kemianteollisuuden raaka-aineet ja uuden sukupolven paperi- ja kartonkituotteet. Metsäteollisuuden muuttuminen ja laitosten monimutkaistuminen sekä jatkuvasti lisääntyvä tiedontarve asettavat yhä suurempia vaatimuksia sekä toiminnanharjoittajien ympäristövastaaville että viranomaisille. Hallinnon jatkuva muutos ja niukkenevat voimavarat voivat johtaa siihen, että käytännön lupa- ja valvontatyöhön jää yhä vähemmän aikaa. Kaakkois-Suomen ELY-keskuksen koordinoima hanke ”Metsäteollisuuden ympäristöstrategia vuoteen 2020 - hallinnon näkökulma” pyrkii vastaamaan edellä mainittuihin haasteisiin strategiatyön avulla. Hankkeen tarkoituksena oli tarkastella metsäteollisuuden ympäristönäkökohtia niistä lähtökohdista, joihin yritys voi vaikuttaa raaka-aineen tulosta tehtaalle ja tuotteen lähdöstä tehtaalta sekä tehtaan perustamisesta sulkemiseen ja jälkihoitoon asti. Tavoitteena oli määritellä toiminnoille toimiva ympäristöstrategia. Strategiassa pyrittiin löytämään yhteisymmärrys toiminnanharjoittajan ja viranomaisen kanssa mm. siitä, miten otetaan käyttöön parhaat käytännöt niin teollisuudessa kuin hallinnossakin, toimitaan uusien BAT-, IED- ja vesienhoitoperiaatteiden mukaisesti sekä edistetään kestävän kehityksen mukaisten tuotteiden markkinoille tuloa ja otetaan ennakointi tavaksi -lähtökohta käyttöön kaikessa toiminnassa. Hanketyössä esille nousseet haasteet ryhmiteltiin aihelueittain kolmeksi pääkohdaksi tärkeysjärjestyksessä: viranomaisen ja teollisuuden tiedonkulun ja tietämyksen parantaminen, lupa-, valvonta- ja hallintoprosessien parantaminen sekä uusien haasteiden kartoittaminen ja niihin reagointi. Haasteiden ratkaisukeinoiksi etsittiin käytännön toimenpiteitä sekä määriteltiin niille vastuutahot. Toimenpiteiksi esitettiin mm. viranomaisen ja teollisuuden yhteisiä koulutuspäiviä, asiantuntijapaneelin perustamista sekä lupamääräysten antamista myös tehtaan tai tuotantoyksikön sulkemisen tai muuttamisen varalle. Riittävien resurssien ja tietotaidon turvaaminen niin hallinnossa kuin teollisuudessa on ehdoton edellytys toimenpiteiden onnistumiselle
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We microscopically and mechanically evaluated the femurs of rats subjected to hindlimb unloading (tail suspension) followed by treadmill training. Female Wistar rats were randomly divided into five groups containing 12-14 rats: control I (118 days old), control II (139 days old), suspended (tail suspension for 28 days), suspended-released (released for 21 days after 28 days of suspension), and suspended-trained (trained for 21 days after 28 days of suspension). We measured bone resistance by bending-compression mechanical tests of the entire proximal half of the femur and three-point bending tests of diaphyseal cortical bone. We determined bone microstructure by tetracycline labeling of trabecular and cortical bone. We found that tail suspension weakened bone (ultimate load = 86.3 ± 13.5 N, tenacity modulus = 0.027 ± 0.011 MPa·m vs ultimate load = 101.5 ± 10.5 N, tenacity modulus = 0.019 ± 0.006 MPa·m in control I animals). The tenacity modulus for suspended and released animals was 0.023 ± 0.010 MPa·m vs 0.046 ± 0.018 MPa·m for trained animals and 0.035 ± 0.010 MPa·m for control animals. These data indicate that normal activity and training resulted in recovered bone resistance, but suspended-released rats presented femoral head flattening and earlier closure of the growth plate. Microscopically, we found that suspension inhibited new bone subperiosteal and endosteal formation. The bone disuse atrophy secondary to hypoactivity in rats can be reversed by an early regime of exercising, which is more advantageous than ordinary cage activities alone.
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Round holes in the ears of MRL mice tend to close with characteristics of regeneration believed to be absent in other mouse strains (e.g., C57BL/6). We evaluated the kinetics and the histopathology of ear wound closure in young (8 weeks old) C57BL/6 and BALB/c mice. We also used middle-aged (40 weeks old) C57BL/6 mice to evaluate the influence of aging on this process. A circular through-and-through hole was made in the ear, photographs were taken at different times after injury and wound area was measured with digital analysis software. The percentages of closed area measured on day 100 were: 23.57 ± 8.66% for young BALB/c mice, 56.47 ± 7.39% for young C57BL/6 mice, and 75.31 ± 23.65% for middle-aged C57BL/6 mice. Mice were sacrificed on days 1, 3, 5, 25, 44, and 100 for histological evaluation with hematoxylin and eosin, Gomori’s trichrome, periodic acid-Schiff, or picrosirius red staining. In young mice of both strains, healing included re-epithelialization, chondrogenesis, myogenesis, and collagen deposition. Young C57BL/6 and BALB/c mice differed in the organization of collagen fibers visualized using picrosirius-polarization. Sebaceous glands and hair follicles regenerated and chondrogenesis was greater in young C57BL/6 mice. In middle-aged C57BL/6 mice all aspects of regeneration were depressed. The characteristics of regeneration were present during ear wound healing in both young BALB/c and young C57BL/6 mice although they differed in intensity and pattern. Greater ear wound closure in middle-aged C57BL/6 mice was not correlated with regeneration.
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This study determined the effects of gallium-aluminum-arsenide laser (GaAlAs), gallium-arsenide laser (GaAs) and Dersani® healing ointment on skin wounds in Wistar rats. The parameters analyzed were: type I and III collagen fiber concentrations as well as the rate of wound closure. Five wounds, 12 mm in diameter, were made on the animals’ backs. The depth of the surgical incision was controlled by removing the epithelial tissue until the dorsal muscular fascia was exposed. The animals were anesthetized with ketamine and xylazine via intraperitoneal injection. The rats were randomly divided into five groups of 6 animals each, according to the treatment received. Group 1 (L4): GaAs laser (4 J/cm²); group 2 (L30): GaAlAs laser (30 J/cm²); group 3 (L60): GaAlAs laser (60 J/cm²); group 4 (D): Dersani® ointment; group 5 (control): 0.9% saline. The applications were made daily over a period of 20 days. Tissue fragments were stained with picrosirius to distinguish type I collagen from type III collagen. The collagen fibers were photo-documented and analyzed using the Quantum software based on the primary color spectrum (red, yellow and blue). Significant results for wound closing rate were obtained for group 1 (L4), 7.37 mm/day. The highest concentration of type III collagen fibers was observed in group 2 (L30; 37.80 ± 7.10%), which differed from control (29.86 ± 5.15%) on the 20th day of treatment. The type I collagen fibers of group 1 (L4; 2.67 ± 2.23%) and group 2 (L30; 2.87 ± 2.40%) differed significantly from control (1.77 ± 2.97%) on the 20th day of the experiment.
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Physical training influences the cells and mediators involved in skin wound healing. The objective of this study was to determine the changes induced by different intensities of physical training in mouse skin wound healing. Ninety male C57BL6 mice (8 weeks old, 20-25 g) were randomized into three physical training groups: moderate (70% VO2max), high (80% VO2max), and strenuous intensity (90% VO2max). Animals trained on a motorized treadmill for 8 weeks (Elesion: physical training until the day of excisional lesion, N = 10) or 10 weeks (Eeuthan: physical training for 2 additional weeks after excisional lesion until euthanasia, N = 10), five times/week, for 45 min. Control groups (CG) trained on the treadmill three times/week only for 5 min (N = 10). In the 8th week, mice were anesthetized, submitted to a dorsal full-thickness excisional wound of 1 cm², and sacrificed 14 days after wounding. Wound areas were measured 4, 7, and 14 days after wounding to evaluate contraction (d4, d7 and d14) and re-epithelialization (d14). Fragments of lesion and adjacent skin were processed and submitted to routine histological staining. Immunohistochemistry against alpha-smooth muscle actin (α-SMA) was performed. Moderate-intensity training (M) until lesion (M/Elesion) led to better wound closure 7 days after wounding compared to controls and M/Eeuthan (P < 0.05), and both moderate-intensity groups showed better re-epithelialization rates than controls (M/Elesion = 85.9%, M/Eeuthan = 96.4% and M/CG = 79.9%; P < 0.05). Sections of M/Elesion and M/Eeuthan groups stained with hematoxylin-eosin, Picrosirius red and α-SMA showed the most mature granulation tissues among all trained groups and controls. Thus, moderate-intensity physical training improves skin wound healing.
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The context of this study is corporate e-learning, with an explicit focus on how digital learning design can facilitate self-regulated learning (SRL). The field of e-learning is growing rapidly. An increasing number of corporations use digital technology and elearning for training their work force and customers. E-learning may offer economic benefits, as well as opportunities for interaction and communication that traditional teaching cannot provide. However, the evolving variety of digital learning contexts makes new demands on learners, requiring them to develop strategies to adapt and cope with novel learning tools. This study derives from the need to learn more about learning experiences in digital contexts in order to be able to design these properly for learning. The research question targets how the design of an e-learning course influences participants’ self-regulated learning actions and intentions. SRL involves learners’ ability to exercise agency in their learning. Micro-level SRL processes were targeted by exploring behaviour, cognition, and affect/motivation in relation to the design of the digital context. Two iterations of an e-learning course were tested on two groups of participants (N=17). However, the exploration of SRL extends beyond the educational design research perspective of comparing the effects of the changes to the course designs. The study was conducted in a laboratory with each participant individually. Multiple types of data were collected. However, the results presented in this thesis are based on screen observations (including eye tracking) and video-stimulated recall interviews. These data were integrated in order to achieve a broad perspective on SRL. The most essential change evident in the second course iteration was the addition of feedback during practice and the final test. Without feedback on actions there was an observable difference between those who were instruction-directed and those who were self-directed in manipulating the context and, thus, persisted whenever faced with problems. In the second course iteration, including the feedback, this kind of difference was not found. Feedback provided the tipping point for participants to regulate their learning by identifying their knowledge gaps and to explore the learning context in a targeted manner. Furthermore, the course content was consistently seen from a pragmatic perspective, which influenced the participants’ choice of actions, showing that real life relevance is an important need of corporate learners. This also relates to assessment and the consideration of its purpose in relation to participants’ work situation. The rigidity of the multiple choice questions, focusing on the memorisation of details, influenced the participants to adapt to an approach for surface learning. It also caused frustration in cases where the participants’ epistemic beliefs were incompatible with this kind of assessment style. Triggers of positive and negative emotions could be categorized into four levels: personal factors, instructional design of content, interface design of context, and technical solution. In summary, the key design choices for creating a positive learning experience involve feedback, flexibility, functionality, fun, and freedom. The design of the context impacts regulation of behaviour, cognition, as well as affect and motivation. The learners’ awareness of these areas of regulation in relation to learning in a specific context is their ability for design-based epistemic metareflection. I describe this metareflection as knowing how to manipulate the context behaviourally for maximum learning, being metacognitively aware of one’s learning process, and being aware of how emotions can be regulated to maintain volitional control of the learning situation. Attention needs to be paid to how the design of a digital learning context supports learners’ metareflective development as digital learners. Every digital context has its own affordances and constraints, which influence the possibilities for micro-level SRL processes. Empowering learners in developing their ability for design-based epistemic metareflection is, therefore, essential for building their digital literacy in relation to these affordances and constraints. It was evident that the implementation of e-learning in the workplace is not unproblematic and needs new ways of thinking about learning and how we create learning spaces. Digital contexts bring a new culture of learning that demands attitude change in how we value knowledge, measure it, define who owns it, and who creates it. Based on the results, I argue that digital solutions for corporate learning ought to be built as an integrated system that facilitates socio-cultural connectivism within the corporation. The focus needs to shift from designing static e-learning material to managing networks of social meaning negotiation as part of a holistic corporate learning ecology.
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The objective of this paper is to definite Historicity in Economic Sciences applying the principles of Entropy and methodological indeterminism. This implies the definition of two kinds of economic universes: one characterized by ergodicity and reversibility of Time and processes and the other by the opposite properties. The first part will deal with the construction of the subject of study and the nature of the proper analysis to these two universes. Taking such dichotomy into account, the second part will examine its implications as regards to the nature of equilibrium, the properties of stability and instability and the closure of the systems.
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The definition of knowledge as justified true belief is the best we presently have. However, the canonical tripartite analysis of knowledge does not do justice to it due to a Platonic conception of a priori truth that puts the cart before the horse. Within a pragmatic approach, I argue that by doing away with a priori truth, namely by submitting truth to justification, and by accordingly altering the canonical analysis of knowledge, this is a fruitful definition. So fruitful indeed that it renders the Gettier counterexamples vacuous, allowing positive work in epistemology and related disciplines.
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Knowledge seems to need the admixture of de facto reliability and epistemic responsibility. But philosophers have had a hard time in attempting to combine them in order to achieve a satisfactory account of knowledge. In this paper I attempt to find a solution by capitalizing on the real and ubiquitous human phenomenon that is the social dispersal of epistemic labour through time. More precisely, the central objective of the paper is to deliver a novel and plausible social account of knowledge-relevant responsibility and to consider the merits of the proposed combination of reliability and responsibility with respect to certain cases of unreflective epistemic subjects.
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Cyanobacteria are able to regulate the distribution of absorbed light energy between photo systems 1 and 2 in response to light conditions. The mechanism of this regulation (the state transition) was investigated in the marine cyanobacterium Synechococcus sp. strain PCC 7002. Three cell types were used: the wild type, psaL mutant (deletion of a photo system 1 subunit thought to be involved in photo system 1 trimerization) and the apcD mutant (a deletion of a phycobilisome subunit thought to be responsible for energy transfer to photo system 1). Evidence from 77K fluorescence emission spectroscopy, room temperature fluorescence and absorption cross-section measurements were used to determine a model of energy distribution from the phycobilisome and chlorophyll antennas in state 1 and state 2. The data confirm that in state 1 the phycobilisome is primarily attached to PS2. In state 2, a portion of the phycobilisome absorbed light energy is redistributed to photo system 1. This energy is directly transferred to photo system 1 by one of the phycobilisome terminal emitters, the product of the apcD gene, rather than via the photo system 2 chlorophyll antenna by spillover (energy transfer between the photo system 2 and photo system 1 chlorophyll antenna). The data also show that energy absorbed by the photo system 2 chlorophyll antenna is redistributed to photo system 1 in state 2. This could occur in one of two ways; by spillover or in a way analogous to higher plants where a segment of the chlorophyll antenna is dissociated from photo system 2 and becomes part of the photo system 1 antenna. The presence of energy transfer between neighbouring photo system 2 antennae was determined at both the phycobilisome and chlorophyll level, in states 1 and 2. Increases in antenna absorption cross-section with increasing reaction center closure showed that there is energy transfer (connectivity) between photosystem 2 antennas. No significant difference was shown in the amount of connectivity under these four conditions.
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Two efficient, regio- and stereo controlled synthetic approaches to the synthesis of racemic analogs of pancratistatin have been accomplished and they serve as the model systems for the total synthesis of optically active 7-deoxy-pancratistatin. In the Diels-Alder approach, an efficient [4+2] cycloaddition of 3,4-methylenedioxyco- nitrostyrene with Danishefsky's diene to selectively form an exo-nitro adduct has been developed as the key step in the construction of the C-ring of the target molecule. In the Michael addition approach, the key step was a conjugate addition of an organic zinc-cuprate to the 3,4-methylenedioxy-(B-nitrostyrene, followed by a diastereocontroUed closure to form the cyclohexane C-ring of the target molecule via an intramolecular nitro-aldol cyclization on a neutral alumina surface. A chair-like transition state for such a cyclization has been established and such a chelation controlled transition state can be useful in the prediction of diastereoselectivity in other related 6-exo-trig nitroaldol reactions. Cyclization of the above products fi^om both approaches by using a Bischler-Napieralski type reaction afforded two lycoricidine derivatives 38 and 50 in good yields. The initial results from the above modeling studies as well as the analysis of the synthetic strategy were directed to a chiral pool approach to the total synthesis of optically active 7-deoxy-pancratistatin. Selective monsilylation and iodination of Ltartaric acid provided a chiral precursor for the proposed key Michael transformation. The outlook for the total synthesis of 7-deoxy-pancratistatin by this approach is very promising.A concise synthesis of novel designed, optically pure, Cz-symmetrical disulfonylamide chiral ligands starting from L-tartaric acid has also been achieved. This sequence employs the metallation of indole followed by Sfj2 replacement of a dimesylate as the key step. The activity for this Cz-symmetric chiral disulfonamide ligand in the catalytic enantioselective reaction has been confirmed by nucleophilic addition to benzaldehyde in the disulfonamide-Ti (0-i-Pr)4-diethylzinc system with a 48% yield and a 33% e.e. value. Such a ligand tethered with a suitable metal complex should be also applicable towards the total synthesis of 7-deoxy-pancratistatin.