Miracle-dz/UniFAR-FTUs huggingface dataset:
Epstein-Barr Virus Nuclear Antigen 3C Augments Mdm2-Mediated p53 Ubiquitination and Degradation by Deubiquitinating Mdm2

ABSTRACT Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is one of the essential latent antigens for primary B-cell transformation. Previous studies established that EBNA3C facilitates degradation of several vital cell cycle regulators, including the retinoblastoma (pRb) and p27KIP proteins, by recruitment of the SCFSkp2 E3 ubiquitin ligase complex. EBNA3C was also shown to be ubiquitinated at its N-terminal residues. Furthermore, EBNA3C can bind to and be degraded in vitro by purified 20S proteasomes. Surprisingly, in lymphoblastoid cell lines, EBNA3C is extremely stable, and the mechanism for this stability is unknown. In this report we show that EBNA3C can function as a deubiquitination enzyme capable of deubiquitinating itself in vitro as well as in vivo. Functional mapping using deletion and point mutational analysis showed that both the N- and C-terminal domains of EBNA3C contribute to the deubiquitination activity. We also show that EBNA3C efficiently deubiquitinates Mdm2, an important cellular proto-oncogene, which is known to be overexpressed in several human cancers. The data presented here further demonstrate that the N-terminal domain of EBNA3C can bind to the acidic domain of Mdm2. Additionally, the N-terminal domain of EBNA3C strongly stabilizes Mdm2. Importantly, EBNA3C simultaneously binds to both Mdm2 and p53 and can form a stable ternary complex; however, in the presence of p53 the binding affinity of Mdm2 toward EBNA3C was significantly reduced, suggesting that p53 and Mdm2 might share a common overlapping domain of EBNA3C. We also showed that EBNA3C enhances the intrinsic ubiquitin ligase activity of Mdm2 toward p53, which in turn facilitated p53 ubiquitination and degradation. Thus, manipulation of the oncoprotein Mdm2 by EBNA3C potentially provides a favorable environment for transformation and proliferation of EBV-infected cells.
Multiband PIFA vehicle telematics antennas

Compact, low-cost antennas for multiband telematics applications on vehicles are described. The multifrequency band antennas are variations on the printed inverted-F antenna (PIFA) principle. One type of PIFA is a compact variation of a conventional antenna while the other is a novel planar version customized for different mounting positions such as bumpers, window, and roof mount. In both derivations the dimensions are small and have been specifically designed for low-cost production. Each antenna was designed for mobile telephone band coverage from 890 to 2100 MHz. Results from free-space simulations are included but more work needs to be carried out as the vehicles have a significant effect on antenna performance. On-vehicle tests are described where the antennas were placed on glass and plastic areas and integrated into an existing multipurpose roof mount antenna.
Human Cytomegalovirus UL97 Phosphorylates the Viral Nuclear Egress Complex

ABSTRACT Herpesvirus nucleocapsids exit the host cell nucleus in an unusual process known as nuclear egress. The human cytomegalovirus (HCMV) UL97 protein kinase is required for efficient nuclear egress, which can be explained by its phosphorylation of the nuclear lamina component lamin A/C, which disrupts the nuclear lamina. We found that a dominant negative lamin A/C mutant complemented the replication defect of a virus lacking UL97 in dividing cells, validating this explanation. However, as complementation was incomplete, we investigated whether the HCMV nuclear egress complex (NEC) subunits UL50 and UL53, which are required for nuclear egress and recruit UL97 to the nuclear rim, are UL97 substrates. Using mass spectrometry, we detected UL97-dependent phosphorylation of UL50 residue S216 (UL50-S216) and UL53-S19 in infected cells. Moreover, UL53-S19 was specifically phosphorylated by UL97 in vitro. Notably, treatment of infected cells with the UL97 inhibitor maribavir or infection with a UL97 mutant led to a punctate rather than a continuous distribution of the NEC at the nuclear rim. Alanine substitutions in both UL50-S216 and UL53-S19 resulted in a punctate distribution of the NEC in infected cells and also decreased virus production and nuclear egress in the absence of maribavir. These results indicate that UL97 phosphorylates the NEC and suggest that this phosphorylation modulates nuclear egress. Thus, the UL97-NEC interaction appears to recruit UL97 to the nuclear rim both for disruption of the nuclear lamina and phosphorylation of the NEC. IMPORTANCE Human cytomegalovirus (HCMV) causes birth defects and it can cause life-threatening diseases in immunocompromised patients. HCMV assembles in the nucleus and then translocates to the cytoplasm in an unusual process termed nuclear egress, an attractive target for antiviral therapy. A viral enzyme, UL97, is important for nuclear egress. It has been proposed that this is due to its role in disruption of the nuclear lamina, which would otherwise impede nuclear egress. In validating this proposal, we showed that independent disruption of the lamina can overcome a loss of UL97, but only partly, suggesting additional roles for UL97 during nuclear egress. We then found that UL97 phosphorylates the viral nuclear egress complex (NEC), which is essential for nuclear egress, and we obtained evidence that this phosphorylation modulates this process. Our results highlight a new role for UL97, the mutual dependence of the viral NEC and UL97 during nuclear egress, and differences among herpesviruses.
MIMO systems with adaptive modulation

We investigate adaptive modulation (AM) schemes in multiple-input-multiple-output (MIMO) systems with various degrees of freedom (D.F.s), such as the subchannel BER, power and spectral efficiency (SE), to be adapted. The adaptation is considered as a nonlinear constrained nonlinear optimization problem in the spatial domain. We obtained both analytical and numerical solutions for uncoded continuous SE systems and showed that the average spectral efficiency (ASE) achieved is insensitive to the number of adaptable D.F. s and which D.F. is adapted. The discrete SE systems are shown to have some penalty compared with the continuous SE cases, but have similar insensitivity.
The Limping Child: Could It Be Lyme Arthritis? Information and Planning for School Nurses

Lyme disease is the most common vector-borne disease in the United States with Lyme arthritis becoming one of the most common symptoms of Lyme disease. It is imperative that school nurses become familiar with vector-borne disease and promptly consider Lyme arthritis to be contemplated as a differential diagnosis of a child presenting to the office with a limp and joint pain and swelling with no history of acute injury. The following article will discuss the overview, implications and management of Lyme arthritis in the school setting and includes a relevant IHP for school nurses to utilize in practice.
Exact and approximate maximum likelihood localization algorithms

Sensors at separate locations measuring either the time difference of arrival (TDOA) or time of arrival (TOA) of the signal from an emitter can determine its position as the intersection of hyperbolae for TDOA and of circles for TOA. Because of measurement noise, the nonlinear localization equations become inconsistent; and the hyperbolae or circles no longer intersect at a single point. It is now necessary to find an emitter position estimate that minimizes its deviations from the true position. Methods that first linearize the equations and then perform gradient searches for the minimum suffer from initial condition sensitivity and convergence difficulty. Starting from the maximum likelihood (ML) function, this paper derives a closed-form approximate solution to the ML equations. When there are three sensors on a straight line, it also gives an exact ML estimate. Simulation experiments have demonstrated that these algorithms are near optimal, attaining the theoretical lower bound for different geometries, and are superior to two other closed form linear estimators.
Dysregulation of Toll-Like Receptor 7 Compromises Innate and Adaptive T Cell Responses and Host Resistance to an Attenuated West Nile Virus Infection in Old Mice

ABSTRACT The elderly are known to have enhanced susceptibility to infections and an impaired capacity to respond to vaccination. West Nile virus (WNV), a mosquito-borne flavivirus, has induced severe neurological symptoms, mostly in the elderly population. No vaccines are available for human use. Recent work showed that an attenuated WNV, a nonstructural (NS) 4B-P38G mutant, induced no lethality but strong immune responses in young (6- to 10-week-old) mice. While studying protective efficacy, we found unexpectedly that old (21- to 22-month) mice were susceptible to WNV NS4B-P38G mutant infection but were protected from subsequent lethal wild-type WNV challenge. Compared to responses in young mice, the NS4B-P38G mutant triggered higher inflammatory cytokine and interleukin-10 (IL-10) production, a delayed γδ T cell expansion, and lower antibody and WNV-specific T cell responses in old mice. Toll-like receptor 7 (TLR7) is expressed on multiple types of cells. Impaired TLR7 signaling in old mice led to dendritic cell (DC) antigen-presenting function compromise and a reduced γδ T cell and regulatory T cell (Treg) expansion during NS4B-P38G mutant infection. R848, a TLR7 agonist, decreased host vulnerability in NS4B-P38G-infected old mice by enhancing γδ T cell and Treg expansion and the antigen-presenting capacity of DCs, thereby promoting T cell responses. In summary, our results suggest that dysregulation of TLR7 partially contributes to impaired innate and adaptive T cell responses and an enhanced vulnerability in old mice during WNV NS4B-P38G mutant infection. R848 increases the safety and efficacy during immunization of old mice with the WNV NS4B-P38G mutant. IMPORTANCE The elderly are known to have enhanced susceptibility to infections and an impaired capacity to respond to vaccination. West Nile virus (WNV), an emerging mosquito-borne flavivirus, has induced severe neurological symptoms more frequently in the elderly population. No vaccines are available for human use. Here, we used an aged mouse model to investigate the protective efficacy of an attenuated WNV, the nonstructural 4B-P38G mutant, which was previously shown to induce no lethality but strong immune responses in young adult mice. Studies that contribute to a mechanistic understanding of immune defects in the elderly will allow the development of strategies to improve responses to infectious diseases and to increase vaccine efficacy and safety in aging individuals.
Control Strategies for Hybrid Electric Vehicles: Evolution, Classification, Comparison, and Future Trends

As hybrid electric vehicles (HEVs) are gaining more popularity in the market, the rule of the energy management system in the hybrid drivetrain is escalating. This paper classifies and extensively overviews the state-of-the-art control strategies for HEVs. The pros and cons of each approach are discussed. From different perspectives, real-time solutions are qualitatively compared. Finally, a couple of important issues that should be addressed in future development of control strategies are suggested. The benefits of this paper are the following: (1) laying down a foundation for future improvements, (2) establishing a basis for comparing available methods, and (3) helping devoted researchers choose the right track, while avoiding doing that which has already been done.
elective labeling of IRAP by the tritiated AT 4 receptor ligand [ 3 H ] Angiotensin IV nd its stable analog [ 3 H ] AL-11

‘AT4 receptors’ through which Angiotensin IV (Ang IV) improves memory acquisition, were recently identified as insulin regulated aminopeptidase (IRAP). Radioligand binding studies have hitherto been performed with iodinated Ang IV in the presence of divalent cation chelators EDTA and 1,10phenanthrolin. Hence, they referred to the apo-form of IRAP. Presently, binding of [3H]Ang IV and [3H]AL-11, a stable Ang IV analog, was compared on Chinese hamster ovary (CHO-K1) and mouse eywords:
An evaluation of a community rehabilitation team

Contemporary specialist mental health policy in Britain emphasises the development of teams dedicated to specific functions such as assertive outreach, crisis management and home treatment. Less attention is devoted to alternative approaches that may augment the illness-oriented perspective of existing specialist policy. This paper describes the rationale and working practices of a community rehabilitation team (CRT) whose work is predicated on the delivery of psychosocial interventions to enhance community integration. A naturalistic design was employed to describe the service in terms of its rationale and target client group, client characteristics, functions performed and interventions offered, and client perceptions of the team. A census of clients referred to the service during its first 12 months of operation was recruited for the study, as were all clinical staff. Data collection methods included surveying client records and case notes, and conducting semi-structured interviews with staff and clients. The findings indicate a team whose interventions are oriented toward optimising levels of independent functioning and promoting social integration through the use of ordinary community resources. Although these specialist functions were evident in the data their delivery within a climate of generic case management created specific tensions for the team. The nature of these tensions is explored in relation to contemporary policy and a case is made for the incorporation of specialist rehabilitation in the current quest for functional services.
Modeling IEEE 802.11 DCF Using Parallel Space-Time Markov Chain: Multi-Hop Ad Hoc Networks

Many performance evaluations for the IEEE 802.11 Distributed Coordination Function (DCF) have been previously reported in the literature; most studies are based on saturation analysis, and a few models under a finite-load condition adopt an M/G/1 queuing system. However, using M/G/1 queuing only considers the first moment of the frame service time to derive the probability of the transmission queue being vacant. In this paper, we model the DCF using the parallel space-time Markov chain, where the frame arrivals are tracked by monitoring the transmission queue during transitions between successive states of the space-time Markov chain. The proposed framework provides the possibility of simultaneously modeling the contention phase, the backoff and post-backoff procedures, and the transmission queue status. The proposed framework is also validated by simulation results.
EBP1, a Novel Host Factor Involved in Primer Binding Site-Dependent Restriction of Moloney Murine Leukemia Virus in Embryonic Cells

ABSTRACT Mouse embryonic cells are unable to support the replication of Moloney murine leukemia virus (MLV). The integrated viral DNA is transcriptionally silenced, largely due to binding of host transcriptional repressors to the primer binding site (PBS) of the provirus. We have previously shown that a PBS DNA-binding repressor complex contains ZFP809 and TRIM28. Here, we identified ErbB3-binding protein 1 (EBP1) to be a novel component of the ZFP809-TRIM28 silencing complex and show that EBP1 depletion reduces PBS-mediated retroviral silencing.
Accurate Bit-Error-Rate Analysis of Bandlimited Cooperative OSTBC Networks Under Timing Synchronization Errors

The distributed multiple-input-multiple-output (MIMO) system (e.g., intercluster communication via cooperating nodes in a wireless sensor network) is a topic of emerging interest. Many previous studies have assumed perfect synchronization among cooperating nodes and identically distributed communication links. Such assumptions are rarely valid in practical operating scenarios. This paper develops an analytical framework for computing the average bit error rate (ABER) of a distributed multiple-input-single-output (MISO) space-time-coded system with binary phase shift keying (BPSK) modulation affected by timing synchronization errors. The cooperating nodes use data pulse-shaping filters for transmission over generalized frequency-nonselective fading channels. As an illustrative example, the performance evaluation of a 2 times 1 MISO system that uses distributed orthogonal space-time block coding (OSTBC) is presented, although this approach can be readily extended to analyze distributed transmit diversity with a larger number of cooperating nodes. We show that under certain conditions, a distributed MISO system with time synchronization errors can still outperform a perfectly synchronized single-input-single-output (SISO) system.
Maximizing Outage Capacity of OFDM Transmit Diversity Systems

Performance analysis of open-loop transmit diversity schemes for orthogonal frequency-division-multiplexing (OFDM) systems is addressed by investigating the outage capacity limits in frequency-selective fading channels. It is shown that the variance of the mutual information provides details on the amount of available diversity, and it suggests guidelines on transmitter design. The optimal delays, in the outage capacity maximization sense, are found for linear and cyclic delay diversity (LDD and CDD) schemes. It is proved that the outage rates for subcarrier diversity (SD) systems are the same as for the optimized CDD case. The effect of spatial correlation on system performance for a uniform linear transmit array is discussed and numerically evaluated.
Identification of Novel Influenza A Virus Proteins Translated from PA mRNA

ABSTRACT Many replication events are involved in the influenza A virus life cycle, and they are accomplished by different virus proteins with specific functions. However, because the size of the influenza virus genome is limited, the virus uses different mechanisms to express multiple viral proteins from a single gene segment. The M2 and NS2 proteins are produced by splicing, and several novel influenza A virus proteins, such as PB1-F2, PB1-N40, and PA-X, have recently been identified. Here, we identified novel PA-related proteins in influenza A virus-infected cells. These newly identified proteins are translated from the 11th and 13th in-frame AUG codons in the PA mRNA and are, therefore, N-terminally truncated forms of PA, which we named PA-N155 and PA-N182, respectively. The 11th and 13th AUG codons are highly conserved among influenza A viruses, and the PA-N155 and PA-N182 proteins were detected in cells infected with various influenza A viruses isolated from different host species, suggesting the expression of these N-truncated PAs is universal in nature among influenza A viruses. These N-truncated PAs did not show polymerase activity when expressed together with PB1 and PB2; however, mutant viruses lacking the N-truncated PAs replicated more slowly in cell culture and had lower pathogenicity in mice than did wild-type virus. These results suggest that these novel PA-related proteins likely possess important functions in the replication cycle of influenza A virus.
Unambiguous video pipeline description motivated by HDR

The transition to High Dynamic Range (HDR) requires new standards for video. Existing standards for SDR have tacitly assumed the CRT's native response characteristics for the Electro-Optical Transfer Function or EOTF, often referred to as `gamma'. Since the EOTF was universal and fixed by the physics of the CRT, SDR standards have been typically expressed in terms of the complementary Opto-Electrical Transfer Function or OETF. Unfortunately, viewing the video pipeline solely in terms of the OETF (e.g., BT.709) and EOTF (e.g., BT.1886) is somewhat ambiguous. The resolution of this ambiguity requires the inclusion of the Opto-Optical Transfer Function or OOTF. This paper explains this ambiguity and why it is important for HDR. It closes with a description of an OOTF for HDR that is compatible with the OOTF of existing SDR standards.
Broad Anti-Hepatitis C Virus (HCV) Antibody Responses Are Associated with Improved Clinical Disease Parameters in Chronic HCV Infection

ABSTRACT During hepatitis C virus (HCV) infection, broadly neutralizing antibody (bNAb) responses targeting E1E2 envelope glycoproteins are generated in many individuals. It is unclear if these antibodies play a protective or a pathogenic role during chronic infection. In this study, we investigated whether bNAb responses in individuals with chronic infection were associated with differences in clinical presentation. Patient-derived purified serum IgG was used to assess the breadth of HCV E1E2 binding and the neutralization activity of HCV pseudoparticles. The binding and neutralization activity results for two panels bearing viral envelope proteins representing either an intergenotype or an intragenotype 1 group were compared. We found that the HCV load was negatively associated with strong cross-genotypic E1E2 binding (P = 0.03). Overall, we observed only a modest correlation between total E1E2 binding and neutralization ability. The breadth of intergenotype neutralization did not correlate with any clinical parameters; however, analysis of individuals with genotype 1 (gt1) HCV infection (n = 20), using an intragenotype pseudoparticle panel, found a strong association between neutralization breadth and reduced liver fibrosis (P = 0.006). A broad bNAb response in our cohort with chronic infection was associated with a single nucleotide polymorphism (SNP) in the HLA-DQB1 gene (P = 0.038), as previously reported in a cohort with acute disease. Furthermore, the bNAbs in these individuals targeted more than one region of E2-neutralizing epitopes, as assessed through cross-competition of patient bNAbs with well-characterized E2 antibodies. We conclude that the bNAb responses in patients with chronic gt1 infection are associated with lower rates of fibrosis and host genetics may play a role in the ability to raise such responses. IMPORTANCE Globally, there are 130 million to 150 million people with chronic HCV infection. Typically, the disease is progressive and is a major cause of severe liver cirrhosis and hepatocellular carcinoma. While it is known that neutralizing antibodies have a role in spontaneous clearance during acute infection, little is known about their role in chronic infection. In the present work, we investigated the antibody response in a cohort of chronically infected individuals and found that a broadly neutralizing antibody response is protective and is associated with reduced levels of liver fibrosis and cirrhosis. We also found an association between SNPs in class II HLA genes and the presence of a broadly neutralizing response, indicating that antigen presentation may be important for the production of HCV-neutralizing antibodies.
Non-Stationary Narrowband MIMO Inter-Vehicle Channel Characterization in the 5-GHz Band

In this paper, we describe measurements and models of 30 &times; 30 narrowband multiple-input-multiple-output (MIMO) vehicle-to-vehicle (V2V) radio propagation channels at 5.3 GHz. Four environments were considered: a campus, a highway, a suburban area, and an urban area. Since the scattering environment may rapidly change in V2V communications, we first investigate the validity of the wide-sense stationarity (WSS) assumption for such channels using the correlation matrix distance (CMD), which is a metric for the characterization of the MIMO channel nonstationarity. Moreover, statistical channel models were developed for these environments, which take into account the non-stationary behavior of the measured V2V channels. The large-scale fading was found to be lognormally distributed, whereas the small-scale fading was characterized by the flexible Weibull distribution. Finally, the non-stationary behavior of both large-scale fading and small-scale fading statistics was investigated.