Initial results on in vivo human coronary MR angiography at 7 T.

Seven tesla (T) MR imaging is potentially promising for the morphologic evaluation of coronary arteries because of the increased signal-to-noise ratio compared to lower field strengths, in turn allowing improved spatial resolution, improved temporal resolution, or reduced scanning times. However, there are a large number of technical challenges, including the commercial 7 T systems not being equipped with homogeneous body radiofrequency coils, conservative specific absorption rate constraints, and magnified sample-induced amplitude of radiofrequency field inhomogeneity. In the present study, an initial attempt was made to address these challenges and to implement coronary MR angiography at 7 T. A single-element radiofrequency transmit and receive coil was designed and a 7 T specific imaging protocol was implemented, including significant changes in scout scanning, contrast generation, and navigator geometry compared to current protocols at 3 T. With this methodology, the first human coronary MR images were successfully obtained at 7 T, with both qualitative and quantitative findings being presented.

Urate-induced acute renal failure and chronic inflammation in liver-specific Glut9 knockout mice.

Plasma urate levels are higher in humans than rodents (240-360 vs. â^¼30 μM) because humans lack the liver enzyme uricase. High uricemia in humans may protect against oxidative stress, but hyperuricemia also associates with the metabolic syndrome, and urate and uric acid can crystallize to cause gout and renal dysfunctions. Thus, hyperuricemic animal models to study urate-induced pathologies are needed. We recently generated mice with liver-specific ablation of Glut9, a urate transporter providing access of urate to uricase (LG9KO mice). LG9KO mice had moderately high uricemia (â^¼120 μM). To further increase their uricemia, here we gavaged LG9KO mice for 3 days with inosine, a urate precursor; this treatment was applied in both chow- and high-fat-fed mice. In chow-fed LG9KO mice, uricemia peaked at 300 μM 2 h after the first gavage and normalized 24 h after the last gavage. In contrast, in high-fat-fed LG9KO mice, uricemia further rose to 500 μM. Plasma creatinine strongly increased, indicating acute renal failure. Kidneys showed tubule dilation, macrophage infiltration, and urate and uric acid crystals, associated with a more acidic urine. Six weeks after inosine gavage, plasma urate and creatinine had normalized. However, renal inflammation, fibrosis, and organ remodeling had developed despite the disappearance of urate and uric acid crystals. Thus, hyperuricemia and high-fat diet feeding combined to induce acute renal failure. Furthermore, a sterile inflammation caused by the initial crystal-induced lesions developed despite the disappearance of urate and uric acid crystals.

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.

Smart antennas in software radio base stations

The application of adaptive antenna techniques to fixed-architecture base stations has been shown to offer wide-ranging benefits, including interference rejection capabilities or increased coverage and spectral efficiency.Unfortunately, the actual implementation ofthese techniques to mobile communication scenarios has traditionally been set back by two fundamental reasons. On one hand, the lack of flexibility of current transceiver architectures does not allow for the introduction of advanced add-on functionalities. On the other hand, theoften oversimplified models for the spatiotemporal characteristics of the radio communications channel generally give rise toperformance predictions that are, in practice, too optimistic. The advent of software radio architectures represents a big step toward theintroduction of advanced receive/transmitcapabilities. Thanks to their inherent flexibilityand robustness, software radio architecturesare the appropriate enabling technology for theimplementation of array processing techniques.Moreover, given the exponential progression ofcommunication standards in coexistence andtheir constant evolution, software reconfigurabilitywill probably soon become the only costefficientalternative for the transceiverupgrade. This article analyzes the requirementsfor the introduction of software radio techniquesand array processing architectures inmultistandard scenarios. It basically summarizesthe conclusions and results obtained withinthe ACTS project SUNBEAM,1 proposingalgorithms and analyzing the feasibility ofimplementation of innovative and softwarereconfigurablearray processing architectures inmultistandard settings.

Spatial processing for frequency diversity schemes

A novel technique to obtain optimum blind spatialprocessing for frequency diversity spread spectrum (FDSS) communicationsystems is introduced. The sufficient statistics for alinear combiner, which prove ineffective due to the interferers frequencycharacteristics, are modified to yield improved detectionunder partial jamming in the spectral domain. Robustness to partialtime jamming is achieved by extending the notion of replicasover the frequency axis to a repetition over the time variable. Analysisand simulations are provided, showing the advantages of usingFDSS with spatial diversity to combat the interference when it isconfined to a narrow frequency band or short time interval relativeto the desired signal extent in either domain.

RDM1, a novel RNA recognition motif (RRM)-containing protein involved in the cell response to cisplatin in vertebrates.

A variety of cellular proteins has the ability to recognize DNA lesions induced by the anti-cancer drug cisplatin, with diverse consequences on their repair and on the therapeutic effectiveness of this drug. We report a novel gene involved in the cell response to cisplatin in vertebrates. The RDM1 gene (for RAD52 Motif 1) was identified while searching databases for sequences showing similarities to RAD52, a protein involved in homologous recombination and DNA double-strand break repair. Ablation of RDM1 in the chicken B cell line DT40 led to a more than 3-fold increase in sensitivity to cisplatin. However, RDM1-/- cells were not hypersensitive to DNA damages caused by ionizing radiation, UV irradiation, or the alkylating agent methylmethane sulfonate. The RDM1 protein displays a nucleic acid binding domain of the RNA recognition motif (RRM) type. By using gel-shift assays and electron microscopy, we show that purified, recombinant chicken RDM1 protein interacts with single-stranded DNA as well as double-stranded DNA, on which it assembles filament-like structures. Notably, RDM1 recognizes DNA distortions induced by cisplatin-DNA adducts in vitro. Finally, human RDM1 transcripts are abundant in the testis, suggesting a possible role during spermatogenesis.

ML estimator and hybrid beamformer for multipath and interference mitigation in GNSS receivers

This paper addresses the estimation of the code-phase(pseudorange) and the carrier-phase of the direct signal received from a direct-sequence spread-spectrum satellite transmitter. Thesignal is received by an antenna array in a scenario with interferenceand multipath propagation. These two effects are generallythe limiting error sources in most high-precision positioning applications.A new estimator of the code- and carrier-phases is derivedby using a simplified signal model and the maximum likelihood(ML) principle. The simplified model consists essentially ofgathering all signals, except for the direct one, in a component withunknown spatial correlation. The estimator exploits the knowledgeof the direction-of-arrival of the direct signal and is much simplerthan other estimators derived under more detailed signal models.Moreover, we present an iterative algorithm, that is adequate for apractical implementation and explores an interesting link betweenthe ML estimator and a hybrid beamformer. The mean squarederror and bias of the new estimator are computed for a numberof scenarios and compared with those of other methods. The presentedestimator and the hybrid beamforming outperform the existingtechniques of comparable complexity and attains, in manysituations, the Cramér–Rao lower bound of the problem at hand.

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.

The role of Receptor Activator of NFKB Ligand (RANKL) in mammary gland development

Abstract : The female reproductive hormones estrogen, progesterone and prolactin control postnatal breast development and are important to breast carcinogenesis. The mechanisms by which they elicit proliferation and morphogenesis remain poorly understood. Using the mouse as a model to study the molecular mechanisms through which hormones elicit morphogenetic changes in the mammary gland in vivo, we found the Receptor Activator of NFκB Ligand, a Tumor Necrosis Factor family member, to be strongly induced by progesterone. Recent publications suggested that hormone dependant RANKURANK signals are involved in the terminal differentiation of mammary gland alveolar buds into lobulo-alveolar structures competent for lactation. I show that in the absence of epithelial RANKL a distinct earlier stage of mammary gland development, side branch formation, is blocked. RANKL acts as a major mediator downstream of progesterone; it is required for progesterone-induced paracrine proliferation and completely rescues the mutant phenotype when ectopically expressed in progesterone receptor (PR) KO mammary epithelia. RANKL is not required for cell autonomous division of estrogen receptor alpha (ERa) /PR positive cells. Cyclin D1, previously implicated as a mediator of RANKL, is not affected by ablation of RANKL and is not required for RANKL-induced paracrine proliferation but for the cell autonomous proliferation. Gene expression arrays to find specific RANKL downstream targets have identified Id4, ElfS and one secreted metalloprotease (Adamtsl8) as potential candidates validated by Q-RT-PCR. Interestingly, Id4 and Adamtsl8 are expressed by the myoepithelial cells. Their expression additionally coincides with RANKL mRNA expression at mid pregnancy, possibly implying a functional contribution of both genes to RANKL mediated sidebranch formation. ElfS in contrast, is found to be strongly expressed by the end of pregnancy supporting recent findings of a prolactin mediated regulation. As for RANKL, this gene was in particular induced in luminal cells. Taken together, I report that progesterone is the major proliferative stimulus in the adult mammary gland eliciting proliferation of ERaJPR positive cells by a cell autonomous, cyclin D1-dependent and a paracrine RANKL-dependent mechanism. My work moreover suggests, that RANKL acts as a major orchestrator affecting different downstream mediators, through which progesterone exerts its effects concomitantly on different cellular compartments. Résumé : Les hormones sexuelles telles que l'oestrogène, la progestérone et la prolactine contrôlent le développement postnatal du sein et sont impliquées dans la cazcinogenèse. Les mécanismes par lesquels elles induisent la prolifération et la morphogénèse demeurent incompris. En utilisant la souris comme modèle, J'ai trouvé que le ligand activateur du récepteur de NFκB, une protéine de la famille du facteur de nécrose des tumeurs, peut être fortement induit par la progestérone. Les publications récentes ont suggéré que cette protéine est nécessaire à la fin de la grossesse, quand les cellules sécrétrices du lait apparaissent. Par des techniques de transplantation d'épithélium, je montre contrairement aux études précédentes, qu'en l'absence de RANKL dans l'épithélium une partie distincte du développement mammaire, la formation de branches latérales, est bloquée. La progestérone agit de manière pazacrine par l'intermédiaire de 12ANKL pour induire la prolifération tandis que la mort cellulaire n'est pas affectée. De plus, l'injection d'une protéine recombinante RANKL dans une souris mutante pour le récepteur à la progestérone induit la prolifération des cellules épithéliales en l'absence de grossesse ; la surexpression de RANKL dans ces mêmes mutants mène à une réversion complète du phénotype. Mes expériences démontrent que la progestérone induit deux types distincts de prolifération. Un premier type direct dans laquelle les cellules positives au récepteur à la progestérone prolifèrent. Cette division cellulaire est alors indépendante de RANKL mais dépendante de la cycline D1. Le second type de prolifération est induit par un mécanisme pazacrine et dépend de RANKL mais pas de la cycline D1. Ici, les cellules négatives au récepteur à la progestérone prolifèrent. Pour détecter des gènes cibles de la voie de signalisation du RANKL, un profil d'expression des gènes a été généré. Les facteurs de transcription Id4, EIf5 et une métalloprotéase sécrétée (Adamtsl8) ont été identifiés en tant que cibles potentielles. D'autres analyses de validation démontrent qu'Id4, Adamtsl8, RANKL mais pas E1f5 sont fortement exprimés au cours de la grossesse, coïncidant avec la formation de branchements latéraux induit par progestérone. EIf5 s'est avéré être exprimé vers la fin de la grossesse appuyant des résultats récents proposant une régulation par la prolactine. Le système canalaire mammaire se compose de couches cellulaires: une couche interne de cellules luminales et une externe de cellules myoépithéliale. Les expériences génétiques d'expression ont révélé que RANKL. et E1f5 sont exprimés dans la partie luminale tandis qu'Id4 et Adamtsl8 sont dans les cellules myoépithéliales. En conclusion, je prouve que la progestérone est le stimulus principal induisant la prolifération dans la glande mammaire d'adulte. Deux mécanismes de prolifération sont impliqués: l'un direct dépendant de la cycline Dl et l'autre paracrine dépendant de RANKI.. Mon travail suggère par ailleurs que RANKL agit en tant que médiateur important, par lequel la progestérone exerce ses effets sur différents compartiments cellulaires tels que la coordination de la prolifération des cellules épithéliales avec la réorganisation de la matrice extracellulaire et de la membrane basale exigées pour la morphogénèse du système canalaire latéral.

Plasmapolttoprosessin kehittäminen ja optimointi

Ydinvoimaloidenprimaarivesikierron puhdistukseen käytetään ioninvaihtohartsia. Käytönjälkeen ioninvaihtohartsi luokitellaan matalaja keskiaktiivisiin jätteisiin. Plasmakäsittelyllä käytetyn ioninvaihtohartsin tilavuutta voidaan pienentää sekä sen orgaaninen luonne poistaa. Plasmakäsittelyn tarkoituksena on hapettaa orgaaninen aines oksideiksi, jotka poistuvat prosessista savukaasuina. Epäorgaaninen aines, joka sisältää radioaktiivisen aineksen, on tarkoitus hapettaa oksideiksi ja sulfideiksi, jotka voidaan kerätä talteen tuhkana. Tässä diplomityössä käsitellään käytetyn ioninvaihtohartsin käsittelyyn suunnitellun plasmapolttoprosessin kehittämistä ja optimointia. Ioninvaihtohartsin plasmakäsittelyssä syntyvien reaktiotuotteiden selvittäminen suoritettiin tarkastelemalla ainetaseita sekä aihetta käsitteleviä tutkimuksia. Näiden perusteella parannettiin jäähdytystä, suunniteltiin jatkuvatoiminen syöttömenetelmä sekä laadittiin toimintaalueen reunaehdot laitteistolle. Koelaitteistossa 6,5 kW:n rfteho syötetään sovitinpiirin ja kuparisen induktiokelan kautta plasmaan. Plasmakaasuna on käytetty hapenja argonin seoskaasua. Plasmapolttoa on seurattu massaspektrometrilla, optisella emissiospektrometrilla, lämpösekä painemittareilla. Laskennan ja kokeiden pohjalta selvitettiin optimaalinen seossuhde plasmakaasulle, paineen ja tehon noston vaikutus hartsin polttonopeuteen sekä jatkuvatoimisen syöttömenetelmän edut panostoimiseen syöttöön. Rfgeneraattorin teho rajoitti jatkuvatoimisen polttonopeuden 130 g/h ja hetkellisen polttonopeuden 175 g/h. Radioaktiivisten aineiden pidätys oli 93,5 % cesiumin osalta. Tulosten perusteella 4 kg/h ioninvaihtohartsia polttavan laitteiston tehon lähteeksi tarvitaan 65 kW rfgeneraattori. Palamattoman hartsin ja tuhkan kulkeutuminen partikkelisuodattimille sekä reaktiotuotteena syntyvien rikinoksidien käsittely vaatii vielä jatkotutkimusta.

Calreticulin levels determine onset of early muscle denervation by fast motoneurons of ALS model mice.

Although the precise signaling mechanisms underlying the vulnerability of some sub-populations of motoneurons in ALS remain unclear, critical factors such as metallo-proteinase 9 expression, neuronal activity and endoplasmic reticulum stress have been shown to be involved. In the context of SOD1(G93A) ALS mouse model, we previously showed that a two-fold decrease in calreticulin (CRT) is occurring in the vulnerable fast motoneurons. Here, we asked to which extent the decrease in CRT levels was causative to muscle denervation and/or motoneuron degeneration. Toward this goal, a hemizygous deletion of the crt gene in SOD1(G93A) mice was generated since the complete ablation of crt is embryonic lethal. We observed that SOD1(G93A);crt(+/-) mice display increased and earlier muscle weakness and muscle denervation compared to SOD1(G93A) mice. While CRT reduction in motoneurons leads to a strong upregulation of two factors important in motoneuron dysfunction, ER stress and mTOR activation, it does not aggravate motoneuron death. Our results underline a prevalent role for CRT levels in the early phase of muscle denervation and support CRT regulation as a potential therapeutic approach.

Kidney-sparing surgery for upper tract urothelial cancer.

PURPOSE OF REVIEW: This article reviews and summarizes current knowledge on kidney-sparing surgery (KSS) for upper tract urothelial carcinoma (UTUC). RECENT FINDINGS: Radical nephroureterectomy (RNU) has been central to the treatment of UTUC for decades, but KSS has been applied to a rising number of patients to preserve renal function. Ablation or resection through flexible ureteroscopy or the percutaneous route seems to provide comparable cancer-specific survival and overall survival to RNU, but the risk of local and bladder recurrence remains relatively high. Segmental ureterectomy is used for low-risk unifocal UTUC with recent studies confirming its oncologic safety and equivalence to RNU. Antegrade or retrograde instillation therapy may be considered as adjuvant treatment after conservative surgery, but their efficacy needs to be proven. Intravesical single-dose chemotherapy is likely to become part of the therapy algorithm of UTUC treated by KSS or RNU to lower bladder seeding and recurrence. Postoperative vigilant radiographic and endoscopic surveillance are obligatory because of the high probability of recurrence. SUMMARY: KSS should be regarded as a valid alternative to RNU in case of technically resectable low-risk upper tract urothelial cell carcinoma, even in case of a normal contralateral kidney. Advances in technology and biological and clinical risk estimation will make the management of UTUC more evidence based thereby lowering overtreatment.

In conditions of limited chromophore supply rods entrap 11-cis-retinal leading to loss of cone function and cell death.

RPE65 is a retinoid isomerase required for the production of 11-cis-retinal, the chromophore of both cone and rod visual pigments. We recently established an R91W knock-in mouse strain as homologous animal model for patients afflicted by this mutation in RPE65. These mice have impaired vision and can only synthesize minute amounts of 11-cis-retinal. Here, we investigated the consequences of this chromophore insufficiency on cone function and pathophysiology. We found that the R91W mutation caused cone opsin mislocalization and progressive geographic cone atrophy. Remnant visual function was mostly mediated by rods. Ablation of rod opsin corrected the localization of cone opsin and improved cone retinal function. Thus, our analyses indicate that under conditions of limited chromophore supply rods and cones compete for 11-cis-retinal that derives from regeneration pathway(s) which are reliant on RPE65. Due to their higher number and the instability of cone opsin, rods are privileged under this condition while cones suffer chromophore deficiency and degenerate. These findings reinforce the notion that in patients any effective gene therapy with RPE65 needs to target the cone-rich macula directly to locally restore the cones' chromophore supply outside the reach of rods.

Nonenhanced arterial spin labeled carotid MR angiography using three-dimensional radial balanced steady-state free precession imaging.

PURPOSE: To optimize and preliminarily evaluate a three-dimensional (3D) radial balanced steady-state free precession (bSSFP) arterial spin labeled (ASL) sequence for nonenhanced MR angiography (MRA) of the extracranial carotid arteries. MATERIALS AND METHODS: The carotid arteries of 13 healthy subjects and 2 patients were imaged on a 1.5 Tesla MRI system using an undersampled 3D radial bSSFP sequence providing a scan time of ∼4 min and 1 mm(3) isotropic resolution. A hybridized scheme that combined pseudocontinuous and pulsed ASL was used to maximize arterial coverage. The impact of a post label delay period, the sequence repetition time, and radiofrequency (RF) energy configuration of pseudocontinuous labeling on the display of the carotid arteries was assessed with contrast-to-noise ratio (CNR) measurements. Faster, higher undersampled 2 and 1 min scans were tested. RESULTS: Using hybridized ASL MRA and a 3D radial bSSFP trajectory, arterial CNR was maximized with a post label delay of 0.2 s, repetition times ≥ 2.5 s (P < 0.05), and by eliminating RF energy during the pseudocontinuous control phase (P < 0.001). With higher levels of undersampling, the carotid arteries were displayed in ≤ 2 min. CONCLUSION: Nonenhanced MRA using hybridized ASL with a 3D radial bSSFP trajectory can display long lengths of the carotid arteries with 1 mm(3) isotropic resolution. J. Magn. Reson. Imaging 2015;41:1150-1156. © 2014 Wiley Periodicals, Inc.