Cibles rétiniennes d'action des médicaments [Retinal drug targets].

Retinal effects of systemically administered drugs are rare due to the hematoretinal barriers that protect the retina from circulating active principles. However, some compounds may have direct or indirect toxic effects on the retina through direct interaction with a specific receptor or due to their accumulation within pigment of uveal cells. In the latter case, toxicity is dose-dependent and may be observed years after cessation of medication, as observed with antimalarial drugs. Anti-infective and anti-inflammatory agents, particularly glucocorticoids, are currently injected peri- or intraocularly. The mechanisms and the exact toxicity of glucocorticoids on the retina remain poorly understood. More recently, anti-VEGF has been specifically developed for the treatment of retinal diseases. However, the long-term blockade of VEGF on normal retinal physiology should be determined taking into account VEGF and VEGF receptors expression in the normal and pathologic retina. Whilst enormous advances are made in the treatment of retinal diseases, basic research is still required to define more accurately the molecular targets of drugs to improve their benefits and reduce their potential side effects.

JXTAnonym: An anonymity layer for JXTA services messaging

With the evolution of the P2P research eld, new problems, such as those related with information security, have arisen. It is important to provide security mechanisms to P2P systems, since it has already become one of the key issues when evaluating them. However, even though many P2P systems have been adapted to provide a security baseline to their underlying applications, more advanced capabilities are becoming necessary. Speci cally, privacy preservation and anonymity are deemed essential to make the information society sustainable. Unfortunately, sometimes, it may be di cult to attain anonymity unless it is included into the system's initial design. The JXTA open protocols speci cation is a good example of this kind of scenario. This work studies how to provide anonymity to JXTA's architecture in a feasible manner and proposes an extension which allows deployed services to process two-way messaging without disclosing the endpoints'identities to third parties.

A robust audio watermarking scheme based on MPEG 1 Layer 3 Compression

This paper describes an audio watermarking scheme based on lossy compression. The main idea is taken from an image watermarking approach where the JPEG compression algorithm is used to determine where and how the mark should be placed. Similarly, in the audio scheme suggested in this paper, an MPEG 1 Layer 3 algorithm is chosen for compression to determine the position of the mark bits and, thus, the psychoacoustic masking of the MPEG 1 Layer 3compression is implicitly used. This methodology provides with a high robustness degree against compression attacks. The suggested scheme is also shown to succeed against most of the StirMark benchmark attacks for audio.

A security layer for JXTA core protocols

JXTA define un conjunto de seis protocolos básicos especialmente adecuados para una computación ad hoc, permanente, multi-hop, peer-to-peer (P2P). Estos protocolos permiten que los iguales cooperen y formen grupos autónomos de pares. Este artículo presenta un método que proporciona servicios de seguridad en los protocolos básicos: protección de datos, autenticidad, integridad y no repudio. Los mecanismos que se presentan son totalmente distribuidos y basados ¿¿en un modelo puro peer-to-peer, que no requieren el arbitraje de un tercero de confianza o una relación de confianza establecida previamente entre pares, que es uno de los principales retos en este tipo de entornos.

Aspirin vs anticoagulation in carotid artery dissection: a study of 298 patients

BACKGROUND: No randomized study has yet compared efficacy and safety of aspirin and anticoagulants in patients with spontaneous dissection of the cervical carotid artery (sICAD). METHODS: Prospectively collected data from 298 consecutive patients with sICAD (56% men; mean age 46 +/- 10 years) treated with anticoagulants alone (n = 202) or aspirin alone (n = 96) were retrospectively analyzed. Admission diagnosis was ischemic stroke in 165, TIA in 37, retinal ischemia in 8, and local symptoms and signs (headache, neck pain, Horner syndrome, cranial nerve palsy) in 80 patients, while 8 patients were asymptomatic. Clinical follow-up was obtained after 3 months by neurologic examination (97% of patients) or structured telephone interview. Outcome measures were 1) new cerebral ischemic events, defined as ischemic stroke, TIA, or retinal ischemia, 2) symptomatic intracranial hemorrhage, and 3) major extracranial bleeding. RESULTS: During follow-up, ischemic events were rare (ischemic stroke, 0.3%; TIA, 3.4%; retinal ischemia, 1%); their frequency did not significantly differ between patients treated with anticoagulants (5.9%) and those treated with aspirin (2.1%). The same was true for hemorrhagic adverse events (anticoagulants, 2%; aspirin, 1%). New ischemic events were significantly more frequent in patients with ischemic events at onset (6.2%) than in patients with local symptoms or asymptomatic patients (1.1%). CONCLUSIONS: Within the limitations of a nonrandomized study, our data suggest that frequency of new cerebral and retinal ischemic events in patients with spontaneous dissection of the cervical carotid artery is low and probably independent of the type of antithrombotic treatment (aspirin or anticoagulants).

Cervical nerve root synovial sarcoma in a child with chromosomal (X;18) translocation. Case report and review of the literature.

We report on an 11-year-old female with a history of cervicobrachialgia and progressive weakness of the right arm. Cervical spine MRI showed an enhancing heterogeneous intradural mass occupying the right C6-C7 foramen. She underwent a right C6-C7 foraminotomy with a complete macroscopic removal of the lesion. Pathological examination revealed a synovial sarcoma. Treatment was completed by chemotherapy and proton radiotherapy, and the girl remained free of symptoms for 3 years. After appearance of new symptoms, a local recurrence was confirmed, and despite aggressive treatment with salvage chemotherapy and radiotherapy, the disease progressed beyond medical control, and the child died, 6 years after diagnosis. Early recognition of this rare entity compared to its more benign differential diagnosis is crucial, as an aggressive management is needed.

Joint physical-MAC layer design of the broadcast channel protocol in adhoc networks

Broadcast transmission mode in ad hoc networks is critical to manage multihop routing or providing medium accesscontrol (MAC)-layer fairness. In this paper, it is shown that ahigher capacity to exchange information among neighbors may beobtained through a physical-MAC cross-layer design of the broadcastprotocol exploiting signal separation principles. Coherentdetection and separation of contending nodes is possible throughtraining sequences which are selected at random from a reducedset. Guidelines for the design of this set are derived for a lowimpact on the network performance and the receiver complexity.

Hiiliteräspalkin kuitulaserhitsaus

Hitsaavassa teollisuudessa kilpailukyvyn säilyttäminen ja mahdollinen parantaminen edellyttää hitsauksen tehokkuuden nostoa. Laserhitsauksen nopeus, tarkkuus, tasainen laatu ja aikaansaatava syvä tunkeuma ovatkin vakiinnuttaneet menetelmän vankan aseman tehokkaana valmistusmenetelmänä. Sähkön ja heliumin hinnan nousu ovat pakottaneet teollisuuden miettimään entistä tehokkaampien ja ympäristöystävällisempien laserlähteiden hankkimista. Kuitulaserin korkea hyötysuhde, hyvä säteenlaatu, suuri teho ja matalat käyttökustannukset ovat herättäneet kiinnostusta laserhitsaavassa teollisuudessa. Diplomityössä keskityttiin kuitulaserhitsauksen soveltamiseen. Työn tavoitteena oli parantaa kuitulaserhitsausmenetelmän ymmärrystä ja saada käsitys siitä, miten valitaan hitsausparametrien arvot, ja soveltuuko kuitulaser teolliseen tuotantoon. Tutkimuksessa pyrittiin löytämään peruskokeilla optimaaliset hitsausparametrit, joilla syntyy hyvin tunkeutunut, vähän huokosia sisältävä, ja ulkoisesti laadukas hitsi, sekä optimaalinen hitsin tunkeumaprofiili. Lopuksi hitsausparametreja testattiin tuotteen hitsauksessa. Kuitulaser soveltuu erinomaisesti hiiliteräksen hitsaukseen ja hyvin erikoislujien terästen hitsaukseen, kun teräksen hiili- ja rikkipitoisuudet ovat matalia. Sillä on laaja parametrialue. Yleisimmät hitsausvirheet ovat vajaa hitsautumissyvyys ja huokoset. Tässä diplomityössä keskityttiin etsimään yhdelle valmistettavalle tuotteelle optimaaliset kuitulaserhitsausparametrit. Kuitulaserin laser- ja prosessiparametrien vaikutusta hitsiin ei ole juurikaan tutkittu. Diplomityön kokeiden perusteella olisi hyvä tehdä eri materiaalien jatkotutkimusta railonvalmistuksen, kuten liitoksen oksidikerroksen ja ilmaraon sekä suojakaasun, vaikutuksesta hitsiin. Kuitulaserin hyvä säteenlaatu ja muut laser-parametrit ovat tuoneet mukanaan prosessiin uusia ilmiöitä, joita on syytä tutkia lisää.

Peripheral Nerve Neuropathy is Associated with a Glial Reaction in the Gracile Nucleus Associated with a regulation of the GABA transporter GAT-1

Allodynia (pain in response to normally non painful stimulation) and paresthesia (erroneous sensory experience) are two debilitating symptoms of neuropathic pain. These stem, at least partly, from profound changes in the non-nociceptive sensory pathway that comprises large myelinated neuronal afferents terminating in the gracile and cuneate nuclei. Further than neuronal changes, well admitted evidence indicates that glial cells (especially in the spinal cord) are key actors in neuropathic pain, in particular the possible alteration in astrocytic capacity to reuptake neurotransmitters (glutamate and GABA). Yet, the possibility of such a changed astrocytic scavenging capacity remains unexplored in the dorsal column pathway. The present study was therefore undertaken to assess whether peripheral nerve injury (spared nerve injury model, SNI) could trigger a glial reaction, and especially changes in glutamate and GABA transporters, in the gracile nucleus. SNI surgery was performed on male Sprague-Dawley rats. Seven days after surgery, rats were used for immunofluorescence (fixation and brain slicing), western-blot (fresh brain freezing and protein extraction) or GABA reuptake on synaptosomes. We found that SNI results in a profound glial reaction in the ipsilateral gracile nucleus. This reaction was characterized by an enhanced immunolabelling for microglial marker Iba1 as well as astrocytic protein GFAP (further confirmed by western-blot, p <0.05, n = 7). These changes were not observed in sham animals. Immunofluorescence and western-blot analysis shows that the GABA transporter GAT-1 is upregulated in the ipsilateral gracile nucleus (p <0.001; n = 7), with no detectable change in GAT-3 or glutamate transporters EAAT-1 and EAAT-2. Double immunoflurescence shows that GAT-1 and GFAP colocalize within the same cells. Furthermore, the upregulation of GFAP and GAT-1 were shown to occur all along the rostrocaudal axis of the gracile nucleus. Finally, synaptosomes from ipsilateral gracile nucleus show an increased capacity to reuptake GABA. Together, the data presented herein show that glial cells in the gracile nucleus react to neuropathic lesion, in particular through an upregulation of the GABA transporter GAT-1. Hence, this study points to role of an increased GABA transport in the dorsal column nuclei in neuropathic pain, calling attention to GAT-1 as a putative future pharmacological target to treat allodynia and paresthesia.

Exploration of the visual system: Part 1: Dissection of the mouse eye for RNA, protein, and histological analyses

Due to the power of genetics, the mouse has become a widely used animal model in vision research. However, its eyeball has an axial length of only about 2 mm. The present protocol describes how to easily dissect the small rodent eye post mortem. This allows collecting different tissues of the eye, i.e., cornea, lens, iris, retina, optic nerve, retinal pigment epithelium (RPE), and sclera. We further describe in detail how to process these eye samples in order to obtain high‐quality RNA for RNA expression profiling studies. Depending on the eye tissue to be analyzed, we present appropriate lysis buffers to prepare total protein lysates for immunoblot and immuno‐precipitation analyses. Fixation, inclusion, embedding, and cryosectioning of the globe for routine histological analyses (HE staining, DAPI staining, immunohistochemistry, in situ hybridization) is further presented. These basic protocols should allow novice investigators to obtain eye tissue samples rapidly for their experiments.

Intraperikaryal neurofilamentous accumulations in a subset of retinal ganglion cells in aged mice that express a human neurofilament gene.

Neurofilamentous changes in select groups of neurons are associated with the degenerative changes of many human age-related neurodegenerative diseases. To examine the possible effects of aging on the neuronal cytoskeleton containing human proteins, the retinas of transgenic mice expressing the gene for the human middle-sized neurofilament triplet were investigated at 3 or 12 months of age. Transgenic mice developed tangle-like neurofilamentous accumulations in a subset of retinal ganglion cells at 12 months of age. These neurofilamentous accumulations, which also involved endogenous neurofilament proteins, were present in the perikarya and proximal processes of large ganglion cells and were predominantly located in peripheral retina. The presence of the human protein may thus confer vulnerability of the cytoskeleton to age-related alterations in this specific retinal cell type and may serve as a model for similar cellular changes associated with Alzheimer's disease and glaucoma.