Exploring the space of histidine containing dipeptides in search of novel efficient RCS sequestering agents.

The study reports a set of forty proteinogenic histidine-containing dipeptides as potential carbonyl quenchers. The peptides were chosen to cover as exhaustively as possible the accessible chemical space, and their quenching activities toward 4-hydroxy-2-nonenal (HNE) and pyridoxal were evaluated by HPLC analyses. The peptides were capped at the C-terminus as methyl esters or amides to favor their resistance to proteolysis and diastereoisomeric pairs were considered to reveal the influence of configuration on quenching. On average, the examined dipeptides are less active than the parent compound carnosine (βAla + His) thus emphasizing the unfavorable effect of the shortening of the βAla residue as confirmed by the control dipeptide Gly-His. Nevertheless, some peptides show promising activities toward HNE combined with a remarkable selectivity. The results emphasize the beneficial role of aromatic and positively charged residues, while negatively charged and H-bonding side chains show a detrimental effect on quenching. As a trend, ester derivatives are slightly more active than amides while heterochiral peptides are more active than their homochiral diastereoisomer. Overall, the results reveal that quenching activity strongly depends on conformational effects and vicinal residues (as evidenced by the reported QSAR analysis), offering insightful clues for the design of improved carbonyl quenchers and to rationalize the specific reactivity of histidine residues within proteins.

Suspicion d'hémorragie sous-arachnoïdienne: place d'un score prédictif dans la stratégie diagnostique actuelle [Usefulness of a predictive score in subarachnoid hemorrhage diagnosis].

Usefulness of a predictive score in subarachnoid hemorrhage diagnosis Nearly half of the patients with non-traumatic subarachnoid hemorrhage (SAH) present with no neurological signs, inducing clinical underestimation of the gravity of their affection. As the outcome of aneurismal SAH is highly dependant on the initial neurological status and the recurrence of untreated hemorrhagic events, these neurologically intact patients stand to suffer the most from delayed diagnosis. Although there is currently no validated predictive score that reliably identifies SAH-induced headache, a combination of clinical criteria derived from a cohort of sudden-onset headache patients should allow risk stratification and identification of those patients requiring further investigation.

Cerebral aneurysm exclusion by CT angiography based on subarachnoid hemorrhage pattern: a retrospective study

Contexte : Identifier les patients avec une hémorragie sous-arachnoïdienne spontanée chez qui l'angio-CT suffit pour exclure des anévrysmes rompus.Méthodes : Une étude rétrospective a été effectuée de tous les patients avec une hémorragie sous-arachnoïdienne qui ont eu un angio-CT ainsi qu'une angiographie par cathéter dans le but d'exclure un anévrysme. Les cas négatifs de l'angio-CT (sans anévrysmes) ont été classés d'après leur schéma hémorragique au CT dans les catégories suivantes : « anévrysmale », « périmésencéphalique » puis « sans hémorragie ».Résultats : Deux-cent-quarante-et-un patients ont été inclus. Une sensibilité de 96.4% et une spécificité de 96.0% ont été observée pour l'exclusion d'anévrysmes par l'angio-CT. Parmi les 78 cas négatifs de l'angio-CT, chacun des 35 cas avec un motif hémorragique périmésencéphalique ou sans hémorragie au CT n'ont pas eu d'anévrysmes démontrés à l'angiographie par cathéter.Conclusions: L'angio-CT est fiable pour exclure les anévrysmes rompus lorsqu'un motif hémorragique périmésencéphalique ou pas d'hémorragie sont visibles au CT à une semaine depuis le début des symptômes.

Enhanced MDIR receiver for space-time dispersive channels

A particular property of the matched desiredimpulse response receiver is introduced in this paper, namely,the fact that full exploitation of the diversity is obtained withmultiple beamformers when the channel is spatially and timelydispersive. This particularity makes the receiver specially suitablefor mobile and underwater communications. The new structureprovides better performance than conventional and weightedVRAKE receivers, and a diversity gain with no needs of additionalradio frequency equipment. The baseband hardware neededfor this new receiver may be obtained through reconfigurabilityof the RAKE architectures available at the base station. Theproposed receiver is tested through simulations assuming UTRAfrequency-division-duplexing mode.

Gliotransmitters Travel in Time and Space.

The identification of the presence of active signaling between astrocytes and neurons in a process termed gliotransmission has caused a paradigm shift in our thinking about brain function. However, we are still in the early days of the conceptualization of how astrocytes influence synapses, neurons, networks, and ultimately behavior. In this Perspective, our goal is to identify emerging principles governing gliotransmission and consider the specific properties of this process that endow the astrocyte with unique functions in brain signal integration. We develop and present hypotheses aimed at reconciling confounding reports and define open questions to provide a conceptual framework for future studies. We propose that astrocytes mainly signal through high-affinity slowly desensitizing receptors to modulate neurons and perform integration in spatiotemporal domains complementary to those of neurons.

Space-time front-ends for RAKE receivers in the FDD mode of UTRA

A unified and general vision of different space-time processors is presented. Many popular receivers can beaccomodated, like V-RAKE receivers, weighted V-RAKE, or spatial narrowband beamforming. By makingappropriate assumptions on the space/time characteristic of the interference it is possible to enhance theperformance of the receiver through spatial/temporal pre-processors. These receivers will be tested in the FDDmode of UTRA.

Hybrid turbo FEC/ARQ systems and distributed space-time coding for cooperative transmission

Cooperative transmission can be seen as a "virtual" MIMO system, where themultiple transmit antennas are in fact implemented distributed by the antennas both at the source and the relay terminal. Depending on the system design, diversity/multiplexing gainsare achievable. This design involves the definition of the type of retransmission (incrementalredundancy, repetition coding), the design of the distributed space-time codes, the errorcorrecting scheme, the operation of the relay (decode&forward or amplify&forward) and thenumber of antennas at each terminal. Proposed schemes are evaluated in different conditionsin combination with forward error correcting codes (FEC), both for linear and near-optimum(sphere decoder) receivers, for its possible implementation in downlink high speed packetservices of cellular networks. Results show the benefits of coded cooperation over directtransmission in terms of increased throughput. It is shown that multiplexing gains areobserved even if the mobile station features a single antenna, provided that cell wide reuse of the relay radio resource is possible.

Induced normothermia attenuates cerebral metabolic distress in patients with aneurysmal subarachnoid hemorrhage and refractory Fever.

BACKGROUND AND PURPOSE: The purpose of this study was to analyze whether fever control attenuates cerebral metabolic distress after aneurysmal subarachnoid hemorrhage (SAH). METHODS: Eighteen SAH patients, who underwent intracranial pressure (ICP) and cerebral microdialysis monitoring and were treated with induced normothermia for refractory fever (body temperature >or=38.3 degrees C, despite antipyretics), were studied. Levels of microdialysate lactate/pyruvate ratio (LPR) and episodes of cerebral metabolic crisis (LPR >40) were analyzed during fever and induced normothermia, at normal and high ICP (>20 mm Hg). RESULTS: Compared to fever, induced normothermia resulted in lower LPR (40+/-24 versus 32+/-9, P<0.01) and a reduced incidence of cerebral metabolic crisis (13% versus 5%, P<0.05) at normal ICP. During episodes of high ICP, induced normothermia was associated with a similar reduction of LPR, fewer episodes of cerebral metabolic crisis (37% versus 8%, P<0.01), and lower ICP (32+/-11 versus 28+/-12 mm Hg, P<0.05). CONCLUSIONS: Fever control is associated with reduced cerebral metabolic distress in patients with SAH, irrespective of ICP.

Transcranial Doppler for predicting delayed cerebral ischemia after subarachnoid hemorrhage.

OBJECTIVE: Transcranial Doppler (TCD) is widely used to monitor the temporal course of vasospasm after subarachnoid hemorrhage (SAH), but its ability to predict clinical deterioration or infarction from delayed cerebral ischemia (DCI) remains controversial. We sought to determine the prognostic utility of serial TCD examination after SAH. METHODS: We analyzed 1877 TCD examinations in 441 aneurysmal SAH patients within 14 days of onset. The highest mean blood flow velocity (mBFV) value in any vessel before DCI onset was recorded. DCI was defined as clinical deterioration or computed tomographic evidence of infarction caused by vasospasm, with adjudication by consensus of the study team. Logistic regression was used to calculate adjusted odds ratios for DCI risk after controlling for other risk factors. RESULTS: DCI occurred in 21% of patients (n = 92). Multivariate predictors of DCI included modified Fisher computed tomographic score (P = 0.001), poor clinical grade (P = 0.04), and female sex (P = 0.008). After controlling for these variables, all TCD mBFV thresholds between 120 and 180 cm/s added a modest degree of incremental predictive value for DCI at nearly all time points, with maximal sensitivity by SAH day 8. However, the sensitivity of any mBFV more than 120 cm/s for subsequent DCI was only 63%, with a positive predictive value of 22% among patients with Hunt and Hess grades I to III and 36% in patients with Hunt and Hess grades IV and V. Positive predictive value was only slightly higher if mBFV exceeded 180 cm/s. CONCLUSION: Increased TCD flow velocities imply only a mild incremental risk of DCI after SAH, with maximal sensitivity by day 8. Nearly 40% of patients with DCI never attained an mBFV more than 120 cm/s during the course of monitoring. Given the poor overall sensitivity of TCD, improved methods for identifying patients at high risk for DCI after SAH are needed.

Evaluation of a novel biomaterial in the suprachoroidal space of the rabbit eye.

PURPOSE: Drug delivery to treat diseases of the posterior segment of the eye, such as choroidal neovascularization and its complications, is hampered by poor intraocular penetration and rapid elimination of the drug from the eye. The purpose of this study was to investigate the feasibility and tolerance of suprachoroidal injections of poly(ortho ester) (POE), a bioerodible and biocompatible polymer, as a biomaterial potentially useful for development of sustained drug delivery systems. METHODS: After tunnelization of the sclera, different formulations based on POE were injected (100 microL) into the suprachoroidal space of pigmented rabbits and compared with 1% sodium hyaluronate. Follow-up consisted of fundus observations, echography, fluorescein angiography, and histologic analysis over 3 weeks. RESULTS: After injection, POE spread in the suprachoroidal space at the posterior pole. It was well tolerated and progressively disappeared from the site of injection without sequelae. No bleeding or retinal detachment occurred. Echographic pictures showed that the material was present in the suprachoroidal space for 3 weeks. Angiography revealed minor pigment irregularities at the site of injection, but no retinal edema or necrosis. Histology showed that POE was well tolerated in the choroid. CONCLUSIONS: POE suprachoroidal injections, an easy, controllable, and reproducible procedure, were well tolerated in the rabbit eye. POE appears to be a promising biomaterial to deliver drugs focally to the choroid and the retina.

Transnational private authority and the participation of workers' organizations in the regulatory space surrounding the employment relationship

Most corporate codes of conduct and multi-stakeholder sustainability standards guarantee workers' rights to freedom of association and collective bargaining, but many authors are sceptical about the concrete impact of codes and standards of this kind. In this paper we use Hancher and Moran's (1998) concept of 'regulatory space' to assess the potential of private transnational regulation to support the growth of trade union membership and collective bargaining relationships, drawing on some preliminary case study results from a project on the impact of the International Finance Corporation's (IFC) social conditionality on worker organization and social dialogue. One of the major effects of neoliberal economic and industrial policy has been the routine exclusion of workers' organizations from regulatory processes on the grounds that they introduce inappropriate 'political' motives into what ought to be technical decision-making processes. This, rather than any direct attack on their capacity to take action, is what seems best to explain the global decline in union influence (Cradden 2004; Howell 2007; Howe 2012). The evidence we present in the paper suggests that private labour regulation may under certain conditions contribute to a reversal of this tendency, re-establishing the legitimacy of workers' organizations within regulatory processes and by extension the legitimacy of their use of economic and social power. We argue that guarantees of freedom of association and bargaining rights within private regulation schemes are effective to the extent that they can be used by workers' organizations in support of a claim for access to the regulatory space within which the terms and conditions of the employment relationship are determined. Our case study evidence shows that certain trade unions in East Africa have indeed been able to use IFC and other private regulation schemes as levers to win recognition from employers and to establish collective bargaining relationships. Although they did not attempt to use formal procedures to make a claim for the enforcement of freedom of association rights on behalf of their members, the unions did use enterprises' adherence to private regulation schemes as a normative point of reference in argument and political exchange about worker representation. For these unions, the regulation was a useful addition to the range of arguments that they could deploy as means to justify their demand for recognition by employers. By contrast, the private regulation that helps workers' organizations to win access to regulatory processes does little to ensure that they are able to participate meaningfully, whether in terms of technical capacity or of their ability to mobilize social power as a counterweight to the economic power of employers. To the extent that our East African unions were able to make an impact on terms and conditions of employment via their participation in regulatory space it was solely on the basis of their own capacities and resources and the application of national labour law.

Motion artifact reduction and vessel enhancement for free-breathing navigator-gated coronary MRA using 3D k-space reordering.

Breathing-induced bulk motion of the myocardium during data acquisition may cause severe image artifacts in coronary magnetic resonance angiography (MRA). Current motion compensation strategies include breath-holding or free-breathing MR navigator gating and tracking techniques. Navigator-based techniques have been further refined by the applications of sophisticated 2D k-space reordering techniques. A further improvement in image quality and a reduction of relative scanning duration may be expected from a 3D k-space reordering scheme. Therefore, a 3D k-space reordered acquisition scheme including a 3D navigator gated and corrected segmented k-space gradient echo imaging sequence for coronary MRA was implemented. This new zonal motion-adapted acquisition and reordering technique (ZMART) was developed on the basis of a numerical simulation of the Bloch equations. The technique was implemented on a commercial 1.5T MR system, and first phantom and in vivo experiments were performed. Consistent with the results of the theoretical findings, the results obtained in the phantom studies demonstrate a significant reduction of motion artifacts when compared to conventional (non-k-space reordered) gating techniques. Preliminary in vivo findings also compare favorably with the phantom experiments and theoretical considerations. Magn Reson Med 45:645-652, 2001.