Assessing cortical bone mechanical properties using collagen proton fraction from ultrashort echo time magnetization transfer (UTE-MT) MRI modeling.

Cortical bone shows as a signal void when using conventional clinical magnetic resonance imaging (MRI). Ultrashort echo time MRI (UTE-MRI) can acquire high signal from cortical bone, thus enabling quantitative assessments. Magnetization transfer (MT) imaging combined with UTE-MRI can indirectly assess protons in the organic matrix of bone. This study aimed to examine UTE-MT MRI techniques to estimate the mechanical properties of cortical bone. A total of 156 rectangular human cortical bone strips were harvested from the tibial and femoral midshafts of 43 donors (62 ± 22 years old, 62 specimens from females, 94 specimens from males). Bone specimens were scanned using UTE-MT sequences on a clinical 3 T MRI scanner and on a micro-computed tomography (μCT) scanner. A series of MT pulse saturation powers (400°, 600°, 800°) and frequency offsets (2, 5, 10, 20, 50 kHz) was used to measure the macromolecular fraction (MMF) utilizing a two-pool MT model. Failure mechanical properties of the bone specimens were measured using 4-point bending tests. MMF from MRI results showed significant strong correlations with cortical bone porosity (R = -0.72, P < 0.01) and bone mineral density (BMD) (R = +0.71, P < 0.01). MMF demonstrated significant moderate correlations with Young modulus, yield stress, and ultimate stress (R = 0.60-0.61, P < 0.01). These results suggest that the two-pool UTE-MT model focusing on the organic matrix of bone can potentially serve as a novel tool to detect the variations of bone mechanical properties and intracortical porosity

Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney.

BackgroundExcess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout therapies; however, their use is limited by drug-drug interactions and off-target toxicity, respectively. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout.MethodssUA levels, fractional excretion of uric acid (FEUA), lesinurad plasma levels, and urinary excretion of lesinurad were measured in healthy volunteers treated with lesinurad. In addition, lesinurad, probenecid, and benzbromarone were compared in vitro for effects on urate transporters and the organic anion transporters (OAT)1 and OAT3, changes in mitochondrial membrane potential, and human peroxisome proliferator-activated receptor gamma (PPARγ) activity.ResultsAfter 6 hours, a single 200-mg dose of lesinurad elevated FEUA 3.6-fold (p < 0.001) and reduced sUA levels by 33 % (p < 0.001). At concentrations achieved in the clinic, lesinurad inhibited activity of URAT1 and OAT4 in vitro, did not inhibit GLUT9, and had no effect on ABCG2. Lesinurad also showed a low risk for mitochondrial toxicity and PPARγ induction compared to benzbromarone. Unlike probenecid, lesinurad did not inhibit OAT1 or OAT3 in the clinical setting.ConclusionThe pharmacodynamic effects and in vitro activity of lesinurad are consistent with inhibition of URAT1 and OAT4, major apical transporters for uric acid. Lesinurad also has a favorable selectivity and safety profile, consistent with an important role in sUA-lowering therapy for patients with gout

The Performance of Quaternary Amplitude Modulation with Quaternary Spreading in the Presence of Interfering Signals

Multiple-access digital communications is considered with direct-sequence spread-spectrum (DS-SS) quadrature amplitude modulation and quaternary spreading in each transmission. Each transmitted signal undergoes attenuation and a delay at a receiver in the additive white Gaussian noise channel. The receiver uses coherent demodulation with a correlation detector synchronized to the one of the K received signals so that the K - 1 other transmissions act as interference. The average probability of error at the output of the detector is determined using Monte Carlo simulation and compared with an approximation in which the interference component in each detection statistic is approximated by a Gaussian random variable. Closed-form expressions are derived for the rst and second moments of the interference under several circumstances. The moments are used with the \u27Gaussian approximation\u27, and the accuracy of the approximation is investigated for each of the circumstances

The Performance of Quaternary Amplitude Modulation with Quaternary Spreading in the Presence of Interfering Signals

Multiple-access digital communications is considered with direct-sequence spread-spectrum (DS-SS) quadrature amplitude modulation and quaternary spreading in each transmission. Each transmitted signal undergoes attenuation and a delay at a receiver in the additive white Gaussian noise channel. The receiver uses coherent demodulation with a correlation detector synchronized to the one of the K received signals so that the K - 1 other transmissions act as interference. The average probability of error at the output of the detector is determined using Monte Carlo simulation and compared with an approximation in which the interference component in each detection statistic is approximated by a Gaussian random variable. Closed-form expressions are derived for the rst and second moments of the interference under several circumstances. The moments are used with the \u27Gaussian approximation\u27, and the accuracy of the approximation is investigated for each of the circumstances

Environmental, biological, and genetic factors influencing local adaptation of pink salmon (Oncorhynchus gorbuscha) in Auke Creek, Alaska

Thesis (Ph.D.) University of Alaska Fairbanks, 2016Pacific salmon form distinct, locally adapted populations because of the spatial and temporal precision with which they home to their natal streams. Local adaptation is recognized as an important component underlying the productivity and sustainability of salmonid populations, yet there remains uncertainty of the scale at which it occurs. This uncertainty was addressed by analysis of demographic, genetic, and experimental data collected from seasonally structured brood lines of Pink Salmon that spawn in Auke Creek, Alaska. An extensive background of research on this system has indicated that the timing of the adult and juvenile migrations is closely aligned with fitness and productivity in this stream; this background provided a framework for synthesizing the results of the analyses to address these questions: (1) What ecological factors influence productivity of the freshwater and marine life history stages; (2) Do these factors suggest a mechanism for evolution of migration time; (3) What are the consequences of disrupting fine-scale local adaptation of migration time? Freshwater productivity appeared to be influenced primarily by competition for spawning habitat, rather than variability in environmental conditions. Marine productivity, conversely, was associated with physical processes that influence survival of juveniles in the nearshore environment. Consistent with these findings, genetic evolution of earlier migration time, which was observed in both adults and juveniles over two generations, appeared to be driven by earlier vernal warming of the nearshore environment. Despite these environmental changes and resulting selection against late migrating fish, recruitment to Auke Creek has remained stable, thereby indicating that seasonal structure of migration time has supported sustained productivity in a changing climate. Experimental relaxation of natural barriers to gene flow that maintain the seasonal structure resulted in intermediate adult migration times in two generations of hybrid fish. These patterns were consistent with an additive genetic basis for migration time and suggest that ecological outbreeding depression is a post-zygotic mechanism that maintains adaptive variation of migration time in Auke Creek. Collectively, these results provide evidence that fine-scale local adaptation can enhance productivity of salmonid populations while providing resilience to climate change.Introduction -- Chapter 1 - Ecological factors influencing lifetime fitness of Pink Salmon (Oncorhynchus Gorbuscha) in an Alaskan stream -- Chapter 2 - Evolution of phenology in a salmonid population: a potential adaptive response to climate change -- Chapter 3 - Local adaptation of phenology revealed in out crosses between spawning segments of a salmonid population -- Conclusions -- Supplementary materials

Poganski motivi u ranokršćanskoj umjetnosti katakomba

Kršćani, radi manjka svoje ikonografije i straha od progona, u najranijim danima koriste jednostavne simbole i već aktualne onovremene poganske motive u svojoj umjetnosti. Poganski mitološki likovi u kršćanskome kontekstu dobivaju novo značenje. Dobar pastir u stilu Orfeja postaje simbol za Krista, kršćanskog Dobrog pastira. Sol Invictus, odnosno nepobjedivo sunce koje simbolizira boga Helija postaje referenca na Krista, spasitelja svijeta koji je pobijedio smrt. Odisej i njegovo mukotrpno putovanje postaju alegorija za Crkvu i njene burne početke. Motiv orantice, kao stari simbol osobe u molitvi postaje u kršćanskome kontekstu simbol pobožnosti i prikaz duše u raju. Općeniti simboli, poput ribe ili gozbe, koji su česti u rimskome svijetu nalaze paralelu u kršćanskim biblijskim pričama te se prirodno uklapaju u kršćansku simboliku bez potrebe za daljnjim preinakama.Because of a lack of developed iconography and a fear of prosecution, early day Christians use simple symbols and current popular pagan motifs of the time in their funerary art. Pagan mythological characters gain a new and deeper meaning when put into a Christian setting. The image of the Good Shepherd in the style of Orpheus becomes a symbol of Christ, the Christian Good Shepherd. Sol Invictus, the unbeatable sun that symbolizes the god Helium becomes a reference to Christ, the savior of the world who conquered death itself. Odysseus and his long and dangerous journey back home becomes an allegory for the Church and its troublesome beginnings. The orans motif, an ancient symbol of prayer, when put into a Christian setting, becomes a symbol of piety and representation of a soul in Heaven. Widespread symbols in the Roman world, such as the fish or banquet scenes, find parallels in biblical stories and therefore naturally fit into Christian art without a need for change