Successful small bowel allotransplantation in dogs with cyclosporine and prednisone

Twelve dogs had transplantation of almost the entire small intestine in the orthotopic location; immunosuppression was with cyclosporine and prednisone. Half the dogs had survival of at least one month, and a third lived for at least four months. Two of the animals are still living after 550 and 555 days. Maintenance of nutrition, and absorption of D-xylose and fat were better than in control animals with an iatrogenic short gut syndrome, but distinctly worse than that of normal dogs. © 1984 by The Williams and Wilkins Co

Total pancreaticoduodenal homotransplantation in dogs immunosuppressed with cyclosporine and steroids

Pancreaticoduodenal transplantation was performed with cyclosporine and steroid immunosuppressive therapy in 10 mongrel dogs that had pancreaticoduodenectomy. There was an average animal survival of 50.6 days and an average duration of normoglycemia of 41.8 days. We suggest that pancreaticoduodenal transplantation, which was abandoned as a clinical procedure 10 years ago, be reconsidered for clinical application. © 1984

Silver buckshot or bullet: is a future 'energy mix' necessary?

To displace fossil fuels and achieve the global greenhouse-gas emissions reductions required to meet the Paris Agreement on climate change, the prevalent argument is that a mix of different low-carbon energy sources will need to be deployed. Here we seek to challenge that viewpoint. We argue that a completely decarbonized, energy-rich and sustainable future could be achieved with a dominant deployment of next-generation nuclear fission and associated technologies for synthesizing liquid fuels and recycling waste. By contrast, non-dispatchable energy sources like wind and solar energy are arguably superfluous, other than for niche applications, and run the risk of diverting resources away from viable and holistic solutions. For instance, the pairing of variable renewables with natural-gas backup fails to address many of the entrenched problems we seek to solve. Our conclusion is that, given the urgent time frame and massive extent of the energy-replacement challenge, half-measures that distract from or stymie effective policy and infrastructure investment should be avoided

Pulmonary ventilation imaging based on 4-dimensional computed tomography: comparison with pulmonary function tests and SPECT ventilation images.

PURPOSE: 4-dimensional computed tomography (4D-CT)-based pulmonary ventilation imaging is an emerging functional imaging modality. The purpose of this study was to investigate the physiological significance of 4D-CT ventilation imaging by comparison with pulmonary function test (PFT) measurements and single-photon emission CT (SPECT) ventilation images, which are the clinical references for global and regional lung function, respectively. METHODS AND MATERIALS: In an institutional review board-approved prospective clinical trial, 4D-CT imaging and PFT and/or SPECT ventilation imaging were performed in thoracic cancer patients. Regional ventilation (V4DCT) was calculated by deformable image registration of 4D-CT images and quantitative analysis for regional volume change. V4DCT defect parameters were compared with the PFT measurements (forced expiratory volume in 1 second (FEV1; % predicted) and FEV1/forced vital capacity (FVC; %). V4DCT was also compared with SPECT ventilation (VSPECT) to (1) test whether V4DCT in VSPECT defect regions is significantly lower than in nondefect regions by using the 2-tailed t test; (2) to quantify the spatial overlap between V4DCT and VSPECT defect regions with Dice similarity coefficient (DSC); and (3) to test ventral-to-dorsal gradients by using the 2-tailed t test. RESULTS: Of 21 patients enrolled in the study, 18 patients for whom 4D-CT and either PFT or SPECT were acquired were included in the analysis. V4DCT defect parameters were found to have significant, moderate correlations with PFT measurements. For example, V4DCT(HU) defect volume increased significantly with decreasing FEV1/FVC (R=-0.65, P<.01). V4DCT in VSPECT defect regions was significantly lower than in nondefect regions (mean V4DCT(HU) 0.049 vs 0.076, P<.01). The average DSCs for the spatial overlap with SPECT ventilation defect regions were only moderate (V4DCT(HU)0.39 ± 0.11). Furthermore, ventral-to-dorsal gradients of V4DCT were strong (V4DCT(HU) R(2) = 0.69, P=.08), which was similar to VSPECT (R(2) = 0.96, P<.01). CONCLUSIONS: An 18-patient study demonstrated significant correlations between 4D-CT ventilation and PFT measurements as well as SPECT ventilation, providing evidence toward the validation of 4D-CT ventilation imaging

Effect of expression of adenine phosphoribosyltransferase on the in vivo anti-tumor activity of prodrugs activated by E. coli purine nucleoside phosphorylase

The use of E. coli purine nucleoside phosphorylase (PNP) to activate prodrugs has demonstrated excellent activity in the treatment of various human tumor xenografts in mice. E. coli PNP cleaves purine nucleoside analogs to generate toxic adenine analogs, which are activated by adenine phosphoribosyl transferase (APRT) to metabolites that inhibit RNA and protein synthesis. We created tumor cell lines that encode both E. coli PNP and excess levels of human APRT, and have used these new cell models to test the hypothesis that treatment of otherwise refractory human tumors could be enhanced by overexpression of APRT. In vivo studies with 6-methylpurine-2′-deoxyriboside (MeP-dR), 2-F-2′-deoxyadenosine (F-dAdo) or 9-β-D-arabinofuranosyl-2-fluoroadenine 5′-monophosphate (F-araAMP) indicated that increased APRT in human tumor cells coexpressing E. coli PNP did not enhance either the activation or the anti-tumor activity of any of the three prodrugs. Interestingly, expression of excess APRT in bystander cells improved the activity of MeP-dR, but diminished the activity of F-araAMP. In vitro studies indicated that increasing the expression of APRT in the cells did not significantly increase the activation of MeP. These results provide insight into the mechanism of bystander killing of the E. coli PNP strategy, and suggest ways to enhance the approach that are independent of APRT

Transparent and flexible fingerprint sensor array with multiplexed detection of tactile pressure and skin temperature

We developed a transparent and flexible, capacitive fingerprint sensor array with multiplexed, simultaneous detection of tactile pressure and finger skin temperature for mobile smart devices. In our approach, networks of hybrid nanostructures using ultra-long metal nanofibers and finer nanowires were formed as transparent, flexible electrodes of a multifunctional sensor array. These sensors exhibited excellent optoelectronic properties and outstanding reliability against mechanical bending. This fingerprint sensor array has a high resolution with good transparency. This sensor offers a capacitance variation ~17 times better than the variation for the same sensor pattern using conventional ITO electrodes. This sensor with the hybrid electrode also operates at high frequencies with negligible degradation in its performance against various noise signals from mobile devices. Furthermore, this fingerprint sensor array can be integrated with all transparent forms of tactile pressure sensors and skin temperature sensors, to enable the detection of a finger pressing on the display

Rapid production of large-area, transparent and stretchable electrodes using metal nanofibers as wirelessly operated wearable heaters

A rapidly growing interest in wearable electronics has led to the development of stretchable and transparent heating films that can replace the conventional brittle and opaque heaters. Herein, we describe the rapid production of large-area, stretchable and transparent electrodes using electrospun ultra-long metal nanofibers (mNFs) and demonstrate their potential use as wirelessly operated wearable heaters. These mNF networks provide excellent optoelectronic properties (sheet resistance of similar to 1.3 O per sq with an optical transmittance of similar to 90%) and mechanical reliability (90% stretchability). The optoelectronic properties can be controlled by adjusting the area fraction of the mNF networks, which also enables the modulation of the power consumption of the heater. For example, the low sheet resistance of the heater presents an outstanding power efficiency of 0.65 W cm(-2) (with the temperature reaching 250 degrees C at a low DC voltage of 4.5 V), which is similar to 10 times better than the properties of conventional indium tin oxide-based heaters. Furthermore, we demonstrate the wireless fine control of the temperature of the heating film using Bluetooth smart devices, which suggests substantial promise for the application of this heating film in next-generation wearable electronics

Intrinsic gain modulation and adaptive neural coding

In many cases, the computation of a neural system can be reduced to a receptive field, or a set of linear filters, and a thresholding function, or gain curve, which determines the firing probability; this is known as a linear/nonlinear model. In some forms of sensory adaptation, these linear filters and gain curve adjust very rapidly to changes in the variance of a randomly varying driving input. An apparently similar but previously unrelated issue is the observation of gain control by background noise in cortical neurons: the slope of the firing rate vs current (f-I) curve changes with the variance of background random input. Here, we show a direct correspondence between these two observations by relating variance-dependent changes in the gain of f-I curves to characteristics of the changing empirical linear/nonlinear model obtained by sampling. In the case that the underlying system is fixed, we derive relationships relating the change of the gain with respect to both mean and variance with the receptive fields derived from reverse correlation on a white noise stimulus. Using two conductance-based model neurons that display distinct gain modulation properties through a simple change in parameters, we show that coding properties of both these models quantitatively satisfy the predicted relationships. Our results describe how both variance-dependent gain modulation and adaptive neural computation result from intrinsic nonlinearity.Comment: 24 pages, 4 figures, 1 supporting informatio

Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish

The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe