Lack of PPCA expression only partially coincides with lysosomal storage in galactosialidosis mice: indirect evidence for spatial requirement of the catalytic rather than the protective function of PPCA

Protective protein/cathepsin A (PPCA) is a pleiotropic lysosomal enzyme that complexes with beta-galactosidase and neuraminidase, and possesses serine carboxypeptidase activity. Its deficiency in man results in the neurodegenerative lysosomal storage disorder galactosialidosis (GS). The mouse model of this disease resembles the human early onset phenotype and results in severe nephropathy and ataxia. To understand better the pathophysiology of the disease, we compared the occurrence of lysosomal PPCA mRNA and protein in normal adult mouse tissues with the incidence of lysosomal storage in PPCA(-/-) mice. PPCA expression was markedly variable among different tissues. Most sites that produced both mRNA and protein at high levels in normal mice showed extensive and overt storage in the knockout mice. However, this correlation was not consistent as some cells that normally expressed high levels of PPCA were unaffected in their storage capability in the PPCA(-/-) mice. In addition, some normally low expressing cells accumulated large amounts of undegraded products in the GS mouse. This apparent discrepancy may reflect a requirement for the catalytic rather than the protective function of PPCA and/or the presence of cell-specific substrates in certain cell types. A detailed map showing the cellular distribution of PPCA in nomal mouse tissues as well as the sites of lysosomal storage in deficient mice is critical for accurate assessment of the effects of therapeutic interventions.     

Breed group effects on milk production of Brazilian crossbred dairy cows

Lactation records (n = 2362) of 1402 crossbred cows in 22 cooperating dairy herds in southeastern Brazil were evaluated. Cows were mixtures of Zebu (Gir, Guzera, and unknown) and European breeding (mostly Holstein). Lactation milk yields were expressed as total, 3050-d, or deviated 305-d yields, either adjusted or unadjusted for days in milk (DIM). Mean DIM was 280. Arithmetic means unadjusted for DIM were 1942, 1666, and 5 kg per record. Milk yields of daughters from sires of 6/8 and 7/8 European breeds were higher than yields of daughters from sires of 5/8 European breeds when data were either adjusted or unadjusted for DIM. The differences associated with breed group of sire were only slightly reduced when records were adjusted for DIM. There was no evidence of a decline in milk yield as the fraction of European breeding of the sire increased from 6/8 to 7/8. For a given breed group of sire, whether the grandsire was purebred or crossbred had no detectable effect. These results should be useful in determining strategies for crossbreeding of dairy cows in tropical areas, particularly when crossbred sires are used.     

NN-based Prediction Interval for Nonlinear Processes Controller

Neural networks (NNs) are extensively used in modelling, optimization, and control of nonlinear plants. NN-based inverse type point prediction models are commonly used for nonlinear process control. However, prediction errors (root mean square error (RMSE), mean absolute percentage error (MAPE) etc.) significantly increase in the presence of disturbances and uncertainties. In contrast to point forecast, prediction interval (PI)-based forecast bears extra information such as the prediction accuracy. The PI provides tighter upper and lower bounds with considering uncertainties due to the model mismatch and time dependent or time independent noises for a given confidence level. The use of PIs in the NN controller (NNC) as additional inputs can improve the controller performance. In the present work, the PIs are utilized in control applications, in particular PIs are integrated in the NN internal model-based control framework. A PI-based model that developed using lower upper bound estimation method (LUBE) is used as an online estimator of PIs for the proposed PI-based controller (PIC). PIs along with other inputs for a traditional NN are used to train the PIC to predict the control signal. The proposed controller is tested for two case studies. These include, a chemical reactor, which is a continuous stirred tank reactor (case 1) and a numerical nonlinear plant model (case 2). Simulation results reveal that the tracking performance of the proposed controller is superior to the traditional NNC in terms of setpoint tracking and disturbance rejections. More precisely, 36% and 15% improvements can be achieved using the proposed PIC over the NNC in terms of IAE for case 1 and case 2, respectively for setpoint tracking with step changes.

     

Telehealth Brain Injury Training for Rural Behavioral Health Generalists: Supporting and Enhancing Rural Service Delivery Networks.

Rural psychologists are frontline primary behavioral health care providers for nearly 60 million Americans, but they face limited access to peer consultation and continuing education. This article describes a program that matched 70 rehabilitation inpatients who had new brain injury with rural clinicians from patients' home communities. Neuropsychologists provided one-on-one training for clinicians through telehealth video teleconferencing. Clinicians showed gains in brain injury knowledge, and clients rated trained providers higher than untrained providers. Families seeking brain injury services can connect with these trained rural providers through a Web site, which receives more than 800 hits per month. Telehealth offers potential for rural clinicians to receive support, reduce professional isolation, gain working knowledge of specialty conditions, and deliver high-quality services for their rural clients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reduction of defects and improvement in the performance of blue phosphor for thick‐dielectric electroluminescent displays using Color‐by‐Blue

Abstract— Defect‐free large‐area inorganic thick‐dielectric EL (TDEL) displays using Color by Blue (CBB) technology have been successfully developed. We have achieved the world's highest blue‐phosphor luminance of 900 cd/m² for a single‐pixel device by using CBB and by optimizing the e‐beam gun configuration and the flow rate of H₂S in the vacuum chamber. By analyzing the defects on panels with triple‐pattern phosphors and CBB panels, we also found that the number of defects on CBB panels can be drastically reduced compared with those on triple‐pattern panels. The defect‐free 17‐in. VGA CBB panels show better characteristics, a high peak luminance of 600 cd/m² and a high contrast ratio of 1000:1, compared with those of triple‐pattern panels.     

Aspirin-triggered 15-epi-lipoxin A4 (ATL) generation by human leukocytes and murine peritonitis exudates: development of a specific 15-epi-LXA4 ELISA

Aspirin (ASA) triggers the formation of 15-epi-lipoxins (15-epi-LXs or ATL [ASA-triggered LX]), which are potent bioactive eicosanoids that may contribute to the therapeutic impact of ASA. To elucidate the role of these new compounds in vivo, it is essential to establish quick and sensitive detection methods. To this end, we prepared an enzyme-linked immunosorbent assay specific for 15-epi-LXA4 that proved to be highly sensitive (IC50 approximately 50 pg, minimum detection approximately 3.5 pg) and stereoselective. The amounts of 15-epi-LXA4 generated by human neutrophils from peripheral blood of healthy volunteers using this enzyme-linked immunosorbent assay were in agreement with those values obtained by liquid chromatography. Formation of 15-epi-LXA4 was cell ratio-dependent during THP-1 (a monocytic leukemia cell line)-neutrophil interactions with ASA-treated cells, and 15-epi-LXA4 was not detected with either cell type alone. Generation of 15-epi-LXA4 was also examined in murine peritonitis with ASA administration. Exudates from ASA-treated mice showed increased production of 15-epi-LXA4 that was diminished by indomethacin, a blocker of ASA-dependent acetylation of prostaglandin G/H synthase. A cytochrome P450 inhibitor administered in the presence of ASA did not prevent 15-epi-LXA4 formation, which suggests that P450 does not significantly contribute to formation of 15-epi-LXA4 in this murine model. These results indicate that the new enzyme-linked immunosorbent assay is both sensitive and selective for 15-epi-LXA4 and that 15-epi-LXA4 is produced by human leukocyte-leukocyte interactions. In addition, 15-epi-LXA4 is generated by inflammatory exudates when ASA is administered during murine peritonitis and when prostaglandin G/H synthase is upregulated and acetylated. This assay should provide rapid means to investigate 15-epi-LXA4 generation in both cellular and animal models.     

Hydrogen bonding stabilizes globular proteins

It is clear that intramolecular hydrogen bonds are essential to the structure and stability of globular proteins. It is not clear, however, whether they make a net favorable contribution to this stability. Experimental and theoretical studies are at odds over this important question. Measurements of the change in conformational stability, delta (delta G), for the mutation of a hydrogen bonded residue to one incapable of hydrogen bonding suggest a stabilization of 1.0 kcal/mol per hydrogen bond. If the delta (delta G) values are corrected for differences in side-chain hydrophobicity and conformational entropy, then the estimated stabilization becomes 2.2 kcal/mol per hydrogen bond. These and other experimental studies discussed here are consistent and compelling: hydrogen bonding stabilizes globular proteins.     

Loss of glucose transport in developing avian red cells

OBJECTIVE: This study aimed to examine the characteristics of intraretinal changes associated with macular holes and epiretinal membranes by scanning retinal thickness analysis. STUDY DESIGN: The study design was a nonconsecutive case series. PATIENTS: Fifty-six eyes of patients who had either a suspected or clinically diagnosed macular hole or epiretinal membrane were recruited. INTERVENTIONS: A commercial prototype of the scanning retinal thickness analyzer (RTA) was used. It projected a laser slit beam onto the retina and scanned it, in 200 or 400 msec, across a 2- x 2-mm area, yielding multiple optical cross sections that were recorded digitally. RESULTS: Epiretinal membranes were detected, and sites of attachment could be identified. Full-thickness holes corresponded to intraretinal cavities in which the inner retinal surface was broken, usually at the center. The majority of eyes with full-thickness macular holes showed increased retinal thickness surrounding the hole. The so-called "cuff of subretinal fluid," however, often was not present by retinal thickness analysis, despite clinical diagnosis to the contrary, even though retinal thickness analysis is capable of detecting such fluid. In 20 (42%) of 47 eyes diagnosed or suspected of having macular holes, scanning retinal thickness analysis showed findings different from those reported by retinal specialists. CONCLUSIONS: Examination of macular holes with the scanning RTA provides useful information in the diagnosis of macular holes in addition to that obtained through conventional techniques. The findings support the idea that many macular holes develop in association with intraretinal cystic changes. The precise chronology of the events remains to be determined.