169,771 research outputs found
Déconstruction, auto-immunité, précarité. De l’intraduisible politique chez Derrida
No full textIn this paper we try to analyze that which in Jacques Derrida’s philosophical and political thinking is called “political untranslatable” through a triple movement described in the late texts: a deconstruction movement, which can be found in his entire works and which, in terms of political philosophy, aims to identify in politics an untranslatable remain that cannot be contained in any binary categories of philosophy; an autoimmune movement, which stretches and complicates deconstruction and which expresses the capacity of western political philosophy concepts to obliterate themselves from their inside. The political untranslatable, in terms of autoimmunity, signifies the difficulty, if not impossibility of transferring these concepts from a historical experience to another. Finally, the precariousness movement completes deconstruction and autoimmune vocabulary and refers to the necessity of considering, in any philosophical composition, the fragility of political, economic or social structures of the globalized world in which we live. The political untranslatable is another name for the rest of our individual and collective lives that resist to any recovery in totalizing ideologies
Fig. 16 in Taxonomic Review Of Euphydryas Maturna (Linnaeus, 1758) (Lepidoptera, Nymphalidae) With Description Of A New Subspecies From Dobrogea (Romania) And Notes On Conservation Biology
No full textFig. 16. Distribution of Euphydryas maturna in Eurasia and in SE EuropePublished as part of Rákosy, L., Pecsenye, K., Mihali, C., Tóth, A. & Varga, Z., 2012, Taxonomic Review Of Euphydryas Maturna (Linnaeus, 1758) (Lepidoptera, Nymphalidae) With Description Of A New Subspecies From Dobrogea (Romania) And Notes On Conservation Biology, pp. 145-161 in Acta Zoologica Academiae Scientiarum Hungaricae 58 (2) on page 151, DOI: 10.5281/zenodo.573571
MEMORY OF CHIRALITY: SYNTHESIS OF ENANTIOPURE SULTAMS DERIVED FROM ALFA-AMINO ACIDS
No full textMemory of Chirality: Synthesis of enantiopure sultams derived from α-amino acids
Cyclic sulfonamides (sultams), analogously to open chain sulfonamides, find important applications in human therapeutics. In particular, as a result of their biological activity and low toxicity, they have been recently employed in several fields of medicine, as drugs or as carriers of more complex molecules. Sultams, for example, are used in the design of potential thrombin inhibitors (1) or novel antiarthritic agents (2), showing a potent inhibitory effects on both cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LO), proving to be effective in several animal arthritic models, without any ulcerogenic activities; β-lactam antibiotics, such as (3) that is an anti-MRSA (Methicillin-resistant Staphylococcus aureus) from a series of 1-β-methyl-2-(naphthosultamyl)methyl cationic carbapenems while 8-hydroxy-[1,6]naphthyridines (4) is an HIV-1 integrase inhibitors.
Scheme 1
Moreover, since the introduction of Oppolzer’s sultam, camphorsultam and saccharin derived 3-alkyl benzosultams are relevant in asymmetric synthesis in many stereoselective transformations and have been wide-spreading used as chiral auxiliaries.
Indeed, due to their importance in asymmetric synthesis and medicinal chemistry, many methodologies have been developed for the synthesis of sultams: intramolecular Diels-Alder reactions, sulphonamide dianion alkylations, radical cyclizations, ring closing metathesis, intramolecular Heck cyclizations, etc.
Recently, our research group has reported a straightforward protocol for the preparation of racemic 3-aryl polyfluorobenzosultams, bearing a carboxylic function in the C-3 position. These compounds are obtained via an intramolecular nucleophilic substitution of a fluorine atom as leaving group .
Scheme 2
Our know-how in the application of the concept of “non-racemic enolates” to the synthesis of non-natural quaternary α-amino acids made us focus our attentions on improving a stereoselective synthesis of benzosultams via chiral enolates.
This reaction showed a significant bias toward the enantioselective non-catalized intramolecular cyclization. Given the results obtained in the application of the “Memory of chirality” (MOC) concept in the asymmetric transposition of 4-nitrobenzene sulfonamides, we turned our attention to the cyclization of (pentafluorobenzene)sulfonamido enolates, since these two reactions present a transition state/intermediate strictly related (Scheme 3).
Scheme 3
Memory of chirality is an emerging strategy for enantioselective synthesis. In general, MOC methods involve destruction of the sole original stereogenic center of a starting material, enantioselective generation of conformationally chiral intermediate, and subsequent enantioselective transformation into a centrally chiral product.
Successful MOC reactions must fulfill three conditions:
• the enantiopure centrally chiral starting materials must be enantioselectively transformed into a conformationally chiral intermediate;
• this chiral intermediate must not racemize during the timescale of the reaction.;
• transformation of the conformationally chiral intermediate back to a centrally chiral product must occur with excellent enantioselectivity (Scheme 4).
Scheme 4
The crucial point of our protocol was the stereoselective cyclization of sulfonamides to enantiopure benzosultams. Preliminary experiments performed on non-racemic L-phenylglycine derivatives showed that the cyclization with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) give the corresponding sultam in good yieds, but with lower ee. (Scheme 2). Therefore, we decided to evaluate the use of an additive in the system sulfonamide-DBU, looking for possible interactions additive-base-substrate capable to induce the formation of a chiral adduct, which can evolve enantioselectively toward the desired benzosultam. In particular good results were obtain by using a basic system 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG) and DBU (Scheme 5).
Scheme 5
Very interesting results were also obtained by using BTMG as sole base: the target sultam was isolated in very high yields and ee and, as the most surprising and interesting feature, in the opposite configuration to that obtained with the other bases.
With this strategy the absolute configuration of the final product can be modulated by simply changing the achiral base, thus influencing the different conformer equilibrium and, eventually, choosing the final absolute configuration starting from a unique sulphonamide enantiomer (Scheme 6).
Scheme 6
Both the enantiomers have been prepared from a unique isomer of the starting sulfonamide. These compounds have been N-functionalized by alkylation under SL-PTC conditions giving the N-alkyl benzo[d]sultams in high yields. All these heterocycles gave, after one or more crystallization, the pure enantiomer allowing us to assign the configuration to the cyclization products by mean of single crystal X-ray analysis. The pure enantiomers of the non-N-alkylated sultams were obtained by deprotection of the recrystallized N-allyl derivative because they did not give preferentiale crystallization (Scheme 7).
Scheme 7
In the way of improving the enantiodivergent course of this process, we applied the best reaction conditions previsioly found to a series of substituted N-(pentafluorobenzene)sulfonyl arylglycine esters. Results indicate that a substituent in the para- or ortho-position on the amino acid aromatic ring modulates the sulphonamide reactivity, depending on the type of the functional group used. In particular, the presence on the aromatic ring of a –M substituent was detrimental to the overall process, decreasing the reaction enantioselectivity: the para-nitro phenylglycine methyl ester, reacted rapidly, but gave the racemic sultam; the ortho-chlorine phenylglycine methyl ester, increasing the steric hindrance near the reactive centre, dramatically reduces the reaction rate. On the other hand, the presence of an EDG on the amino acid aromatic ring, such as methoxy, benzyloxy or phenyl, resulted in a quasi-complete enantioselectivity (Scheme 8). Even in this case, we obtained the corresponding benzosultams with retention of configuration by using the basic system (A=BTMG/DBU), and with inversion of configuration when we use the B=TBMG alone.
Scheme 8
The behavior of NH sulfonamides shown in the presence of hindered organic bases, open the possibility to study the synthesis under MOC conditions of several amino acid derivatives, without the need of introducing two different N-activating groups, thus avoiding the cleavage step of one of them.
We have also reported the synthesis of novel enantiopure chiral benzo[d]sultams bearing in the Cα position an alkyl chain, thus having a less acidic Hα than that of phenylglycine. N-Unsubstituted (polifluoro) benzenesulfonamides derived from these amino acids, differently from phenylglycine derivatives, did not react under the action of any base, but good results were obtained by using the corresponding N-alkyl sulfonamides and DBU as a base at low temperatures.
Initially we investigate the synthesis of benzosultams derive from N-(pentafluorobenzene)sulfonyl phenylalanine. The cyclization reaction by using DBU gave, together with the desired sultam, relevant amounts of by-products derivated from nucleophilic attack of DBU on the fluorinated aromatic ring. To eliminate in the cyclization process any interference from the SNAr, which reduces the amount of the target sultam, we decided to synthesize new and more versatile sulfonamides bearing in the 4’ position a bromine or a hydrogen atom instead of the fluorine atom. The cyclization of this differently substituted sulfonamides, gave good yields and ee’s of the resulting benzosultams. In these cases the retention R sultam was the major enantiomer isolated (Scheme 9).
Scheme 9
This strategy has been successfully applied to different optically pure α-amino acid derivatives (alanine, leucine, methionine, and tyrosine), thus performing the synthesis of enantioenriched polyfluorobenzo[d]sultams in few steps (Table 1).
Table 1
R1 X t (h) (%) ee (%)
a ArO-Phe Tyr Br 7 87 99
b ArO-Phe Tyr H 28 75 99
c Me Ala Br 24 83 35
d Me Ala H 5 day 75 27
e iPr Leu Br 5 day 42 95
f iPr Leu H 1 week 30 69
g MeS(CH2)2 Met Br 18 70 57
h MeS(CH2)2 Met H 24 52 37
In conclusion, in this thesis I have described the MOC stereodivergent synthesis of a series of enantiomerically enriched polyfluorobenzo[d]sultams, which were obtained in good to excellent yields, using very mild reaction conditions.
The interest of this protocol resides in the possibility of making use of the chirality of a starting sulfonamide single enantiomer to synthesize the target sultams in both absolute configurations.
The choice of the organic base system is the determining factor to direct the cyclization toward either enantiomer. In fact, the steric hindrance of the base regulates its access to the α-hydrogen, that can be approached alternatively through an inter- or an intramolecular attack. A further peculiarity of this protocol is the use, as starting compounds, of a α-amino acid derivatives bearing a mono-substituted sulfonamide NH function, in the case of phenylglycine derivatives, or N-alkylsulfonamides when the starting compound is an aliphatic derived α-amino acid
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Mitomycin C in highly myopic eyes - Author reply
No full textOphthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
Highly stereoselective intramolecular α-arylation of self-stabilized non-racemic enolates : synthesis of α-quaternary α-amino acid derivatives
No full textThe 'one-pot' stereoselective conversion of N-(4-nitrobenzene)-sulfonyl-alpha-amino acid tert-butyl esters into the corresponding N-alkyl-alpha-(4-nitrophenyl)-alpha-amino esters has been realized through N-alkylation of the starting amido esters, followed by N-C(alpha) migration of the p-nitrophenyl group and the loss of sulfur dioxide; the asymmetric induction is determined by an intermediate non-racemic enolate, without the need of an external source of chirality
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
A Multi-Language Comparison of Influences on Author Verification using Character N-Grams
No full textWe create a new multi-language corpus for author verification based on Wikipedia talkpages, and evaluate the influence that differences in topic and time have on character n-gram author profiles. Topic alignment between two texts is found to increase author verification precision, and an authors writing style is found to change over time, but not more significantly after 3 years than after 1 year.Information ArchitectureWISElectrical Engineering, Mathematics and Computer Scienc
A 0.12mm<sup>2</sup> Wien-Bridge Temperature Sensor with 0.1°C (3σ) Inaccuracy from -40°C to 180°C
No full text Resistor-based temperature sensors can achieve much higher resolution and energy efficiency than conventional BJT-based sensors [1], but they typically occupy more area (> 0.25 mm 2 ) and have lower operating temperatures (le 125 {circ} {C}) [2]-[4]. This work describes a 0.12mm 2 resistor-based sensor that uses a Wien-bridge (WB) filter to achieve 0.1 {circ} {C} (3 sigma) inaccuracy from - 40 {circ} {C} to 180 {circ} {C}. Compared to a state-of-the-art WB sensor [4], it occupies 6 × less area and achieves comparable relative accuracy over a 76% wider operating range. Session 10.3 Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Electronic InstrumentationMicroelectronic
A ±25A Versatile Shunt-Based Current Sensor with 10kHz Bandwidth and ±0.25% Gain Error from -40°C to 85°C Using 2-Current Calibration
No full textAccurate current sensing is critical in many industrial applications, such as battery management and motor control. Precise shunt-based current sensors have been reported with gain errors of less than 1% over the industrial temperature range (-40°C to 85°C) [1]–[4]. However, since they are intended for coulomb counting, their bandwidth is limited to a few tens of Hz, making them unsuitable for battery impedance or motor-current sensing. This paper presents a current sensor with a wide (10kHz) bandwidth and a tunable temperature compensation scheme (TCS), which allows it to be flexibly used with different types of shunts while maintaining high accuracy. A low-cost room-temperature calibration scheme is proposed to optimize gain flatness over temperature by exploiting the shunt's self-heating at large currents. Over the industrial temperature range and a ±25A current range, it achieves state-of-the-art gain error (±0.25%) with both low-cost PCB and stable metal-alloy shunts.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Electronic InstrumentationMicroelectronic
- …
