Explore the vast range of titles available.

Background. Progressive multifocal leukoencephalopathy (PML) in natalizumab-treated MS patients is linked to JC virus (JCV) infection. JCV sequence variation and rearrangements influence viral pathogenicity and tropism. To better understand PML development, we analyzed viral DNA sequences in blood, CSF and/or urine of natalizumabtreated PML patients. Methods. Using biofluid samples from 17 natalizumab-treated PML patients, we sequenced multiple isolates of the JCV noncoding control region (NCCR), VP1 capsid coding region, and the entire 5 kb viral genome. Results. Analysis of JCV from multiple biofluids revealed that individuals were infected with a single genotype. Across our patient cohort, multiple PML-associated NCCR rearrangements and VP1 mutations were present in CSF and blood, but absent from urine-derived virus. NCCR rearrangements occurred in CSF of 100% of our cohort. VP1 mutations were observed in blood or CSF in 81% of patients. Sequencing of complete JCV genomes demonstrated that NCCR rearrangements could occur without VPl mutations, but VP1 mutations were not observed without NCCR rearrangement. Conclusions. These data confirm that JCV in natalizumab-PML patients is similar to that observed in other PML patient groups, multiple genotypes are associated with PML, individual patients appear to be infected with a single genotype, and PML-associated mutations arise in patients during PML development.

Over half of adults are seropositive for JC polyomavirus (JCV), but rare individuals develop progressive multifocal leukoencephalopathy (PML), a demyelinating JCV infection of the central nervous system. Previously, PML was primarily seen in immunosuppressed patients with AIDS or certain cancers, but it has recently emerged as a drug safety issue through its association with diverse immunomodulatory therapies. To better understand the relationship between the JCV life cycle and PML pathology, we studied autopsy brain tissue from a 70-year-old psoriasis patient on the integrin alpha-L inhibitor efalizumab following a ~2 month clinical course of PML. Sequence analysis of lesional brain tissue identified PML-associated viral mutations in regulatory (non-coding control region) DNA, capsid protein VP1, and the regulatory agnoprotein, as well as 9 novel mutations in capsid protein VP2, indicating rampant viral evolution. Nine samples, including three gross PML lesions and normal-appearing adjacent tissues, were characterized by histopathology and subject to quantitative genomic, proteomic, and molecular localization analyses. We observed a striking correlation between the spatial extent of demyelination, axonal destruction, and dispersion of JCV along white matter myelin sheath. Our observations in this case, as well as in a case of PML-like disease in an immunocompromised rhesus macaque, suggest that long-range spread of polyomavirus and axonal destruction in PML might involve extracellular association between virus and the white matter myelin sheath.

A mass and energy balance approach was used to characterize the performance of parallel fan-powered terminal units (FPTUs) with fixed airflow for applications in building simulation programs. The approach included developing relevant mass and energy balance equations for each component--heating coil, fan/motor combination, and mixer--in a parallel fan powered terminal unit. Two locations of the heating coil were considered. One location, designated as the traditional configuration, was at the discharge of the unit. The second location, designated as the alternative configuration, was at the secondary air inlet. Fixed-airflow parallel fan-powered terminal units use fan motors that include either permanent split capacitor motors controlled by silicon controlled rectifiers or electronically commutated motors. This paper demonstrates how to incorporate fan/motor combination performance models for both permanent split capacitor and electronically commutated motors into the mass and energy balance approach. These fan models were developed from performance data provided by multiple FPTU manufacturers. The fan/motor performance data included an FPTU, a fan airflow range from 250 to 3500 [ft.sup.3]/min (0.118 to 1.65 [m.sup.3]/s), and a motor size range from 0.333 to 1 hp (249 to 746 W). Leakage was included in the models. The system was implemented in Engineering Equation Solver (EES) and results provided to illustrate the effect of leakage in both cooling and heating operations.

A traditional mass and energy balance component approach was used to characterize the performance of fixed-airflow series fan-powered terminal units for applications in building simulation programs. The approach included developing relevant energy and mass balance equations for the components in a fan-powered terminal unit-heating coil, fan/motor combination, and mixer. Fan motors that included permanent-split-capacitor motors controlled by silicon-controlled rectifiers or electronically commutated motors were included in the model development. The paper demonstrates how to incorporate the fan/motor combination performance models for both permanent-split-capacitor and electronically commutated motors into the mass and energy balance approach. The fan models were developed from performance data that were provided by multiple fan-powered terminal unit manufacturers. The fan/motor performance data included a fan airflow range from 250to 3500[ft.sup.3]/min (0.118 to 1.65 [m.sup.3]/s) and a motor size range from 0.333 to 1 hp (248.6 to 745.7 W).

Data on the performance of fan/motor combinations used in fan-powered terminal units (FPTUs) were evaluated, and relationships were developed between fan/motor efficiency and fan total pressure as well as fan motor power and fan airflow. All fan motors were permanent split capacitor, with the speed of the motors being altered with silicon-controlled rectifiers (SCRs). Three manufacturers provided detailed experimental data on 12 fan/motor combinations employed in commercially available FPTUs. The fan motors ranged in size from 1/8 hp (93 W) to 1 hp (746 W). The maximum fan airflows ranged from 690 to 4524ft super( 3)/min (0.33 to 2.14 m super( 3)/s). Data were collected by each manufacturer and provided to the authors. The performance data included SCR voltage, discharge static pressure, airflow, volts, amps, volt-amps, power factor, power, motor speed, motor size, and power divided by airflow. Data were also provided on fan discharge area and motor size. A linear relationship between fan/motor total efficiency and fan total pressure was inferred for the units evaluated. By use of the definition of \"fan efficiency,\" it was also shown that the relationship between fan motor power and fan airflow should also be linear. The correlations developed should be in a form that can be readily used in energy simulation programs to better estimate the performance of FPTUs.

Four manufacturers provided detailed performance data on 36 fan/motor combinations applied in commercially available series and parallel fan-powered terminal units. Data were provided for fan static discharge pressures ranging from 0.1 to 0.75 in. w.g. The model developed had two components. First, the data for static discharge pressures ranging from 0.1 to 0.5 in. w.g. were used to develop a correlation between the full-load power and the maximum airflow of the fan/motor combinations. These data were fit with a simple linear regression model. Second, part-load power and airflow data were evaluated over a wide range of controller settings for each fan/motor combination. The data were normalized to the airflow and power corresponding to the maximum controller setting for each static pressure. It was found that the normalized data for those fan motors whose full maximum power operations were less than 80% of the rating of the motor were problematic and were not used in the part-load evaluation. The normalized power and airflow were fit with a third-degree polynomial.

Hepatitis δ virus (HDV) replicates its circular RNA genome via a rolling circle mechanism. During this process, cis-acting ribozymes cleave adjacent upstream sequences and thereby resolve replication intermediates to unit-length RNA. The subsequent ligation of these 5′OH and 2′,3′-cyclic phosphate termini to form circular RNA is an essential step in the life cycle of the virus. Here we present evidence for the involvement of a host activity in the ligation of HDV RNA. We used both HDV and hammerhead ribozymes to generate a panel of HDV and non-HDV RNA substrates that bear 5′-hydroxyl and 2′,3′-cyclic phosphate termini. We found that ligation of these substrates occurred in host cells, but not in vitro or in Escherichia coli. The host-specific ligation activity was capable of joining RNA in both bimolecular and intramolecular reactions and functioned in a sequence-independent manner. We conclude that mammalian cells contain a default pathway that efficiently circularizes ribozyme processed RNAs. This pathway could be exploited in the delivery of stable antisense and decoy RNA to the nucleus.

Human papillomaviruses (HPVs) are associated with the majority of cervical cancers and encode a transforming protein, E6, that interacts with the tumor suppressor protein p53. Because E6 has p53-independent transforming activity, the yeast two-hybrid system was used to search for other E6-binding proteins. One such protein, E6BP, interacted with cancer-associated HPV E6 and with bovine papillomavirus type 1 (BPV-1) E6. The transforming activity of BPV-1 E6 mutants correlated with their E6BP-binding ability. E6BP is identical to a putative calcium-binding protein, ERC-55, that appears to be localized in the endoplasmic reticulum.

Progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease caused by JC virus (JCV) infection of oligodendrocytes, may develop in patients with immune disorders following reactivation of chronic benign infection. Mutations of JCV capsid viral protein 1 (VP1), the capsid protein involved in binding to sialic acid cell receptors, might favor PML onset. Cerebrospinal fluid sequences from 37/40 PML patients contained one of several JCV VP1 amino acid mutations, which were also present in paired plasma but not urine sequences despite the same viral genetic background. VP1-derived virus-like particles (VLPs) carrying these mutations lost hemagglutination ability, showed different ganglioside specificity, and abolished binding to different peripheral cell types compared with wild-type VLPs. However, mutants still bound brain-derived cells, and binding was not affected by sialic acid removal by neuraminidase. JCV VP1 substitutions are acquired intrapatient and might favor JCV brain invasion through abrogation of sialic acid binding with peripheral cells, while maintaining sialic acid-independent binding with brain cells.

A performance model of series fan-powered terminal units (FPTUs) was developed by combining individual component models of the heating coil, fan/motor combination, and mixer using a basic mass and energy balance approach. The fans and motors for the FPTUs were modeled as a combined fan/motor assembly based on prior published work (O'Neal 2015; O'Neal et al. 2015a, 2015b). All the fan motors were electronically commutated motors (ECMs) and covered a range in size from 0.333 to 1 hp (248 to 746 W). The fan/motor combinations in the FPTU could vary airflow to the zone to meet variation in the zone loads. Two control approaches in cooling mode operations were modeled; both approaches provided for control of high enough supply air temperature at high cooling loads to eliminate condensation on registers and at low cooling loads to prevent cold drafts in the zone. One control approach linearly varied discharge temperature and the second linearly varied primary airflow over the cooling range of the zone. Both algorithm eliminated the need to iterate in each simulation time step to obtain a solution for the supply airflow. The performance models were prototyped using Engineering Equation Solver. Sample calculations were provided over the entire expected operating range of heating, cooling, and dead band in field applications, along with a step-by-step explanation of the necessary equations needed for the model implementation. The model can be used to estimate the energy consumption in a variable-air-volume system that has variable-airflow series FPTUs. The modeling methodology can be used directly to improve current building simulation programs that do not allow for estimating the energy use of variable-airflow FPTUs.