Antibodies that neutralize cytomegalovirus (CMV) entry into fibroblasts are predominantly directed against epitopes within virion glycoproteins that are required for attachment and entry. However, the mechanism of CMV entry into epithelial and endothelial cells differs from fibroblast entry. Using assays that simultaneously measured neutralizing activities against CMV entry into fibroblasts and epithelial cells, we found that human immune sera and CMV-hyperimmuneglobulins have on average 48-fold higher neutralizing activities against epithelial cell entry compared to fibroblast entry, suggesting that natural CMV infections elicit neutralizing antibodies that are epithelial entry-specific. This activity could not be adsorbed with recombinant gB. The Towne vaccine and the gB/MF59 subunit vaccine induced epithelial entry-specific neutralizing activities that were on average 28-fold (Towne) or 15-fold (gB/MF59) lower than those observed following natural infection. These results suggest that CMV vaccine efficacy may be enhanced by induction of epithelial entry-specific neutralizing antibodies.

In this paper we derive in great detail the formula for count rates of gamma-ray bursts (GRBs) in the framework of fireballs, in terms of the integral of time, where the Doppler effect of the expanding fireball surface is the key factor concerned. Effects arising from the limit on the time delay due to the limited emitting areas on the fireball surface and other factors are investigated. Our analysis shows that the formula for the count rate of fireballs can be expressed as a function of , which is the observation timescale relative to the dynamical timescale of the fireball defined by R c /c, where R c is the fireball radius measured at an associated local time. The profile of light curves of fireballs depends only on the relative timescale, entirely independent of the real timescale and the real size of the objects. It displays in detail how a cutoff tail or a turnover feature (called the cutoff tail problem) in the decay phase of a light curve can arise. This feature is a consequence of a hot spot on the fireball surface, moving toward the observer, and has been observed in a few cases previously. Local pulses suddenly dimming produce light curves bearing a certain decay form (called a standard decay form) and exhibiting a sharp feature at their peaks. Light curves arising from gradually dimming local pulses are smooth at their peaks, and their profiles in the decay phase will obviously deviate from the standard form when the width of the local pulse is large enough. It is observed that light curves arising from relatively short local pulses should be the same, entirely independent of the local pulse shape. The impact of the rest-frame radiation form and of the variance of the form on the profile of light curves is insignificant, while the impact on the magnitude of the light curves is obvious. By performing fits to the count-rate light curves of six sample sources, we show how to obtain some physical parameters from the observed profile of the count rate of GRBs and show that there do exist some GRBs for which the profiles of their count rate light curves can be described by the formula provided. In addition, the analysis reveals that the Doppler effect of fireballs could lead to a power-law relationship between the FWHM of pulses and energy, which has been observed previously by many authors.

Congenital human cytomegalovirus infections are the major infectious cause of birth defects in the United States. How this virus crosses the placenta and causes fetal disease is poorly understood. Guinea pig cytomegalovirus (GPCMV) is a related virus that provides an important model for studying cytomegaloviral congenital transmission and pathogenesis. In order to facilitate genetic analysis of GPCMV, the 232kb GPCMV genome was cloned as an infectious bacterial artificial chromosome (BAC). The BAC vector sequences were flanked by LoxP sites to allow efficient excision using Cre recombinase. All initial clones contained spontaneous deletions of viral sequences and reconstituted mutant viruses with impaired growth kinetics in vitro. The deletions in one BAC were repaired using Escherichia coli genetics. The resulting repaired BAC reconstituted a virus with in vitro replication kinetics identical to the wild type parental virus; moreover, its genome was indistinguishable from that of the wild type parental virus by restriction pattern analysis using multiple restriction enzymes. These results suggest that the repaired BAC is an authentic representation of the complete GPCMV genome. It should provide a valuable tool for evaluating the impact of genetic modifications on the safety and efficacy of live attenuated vaccines and for identifying genes important for congenital transmission and fetal disease.

A sub-array of the Large High Altitude Air Shower Observatory (LHAASO), KM2A is mainly designed to observe a large fraction of the northern sky to hunt for γ-ray sources at energies above 10 TeV. Even though the detector construction is still underway, half of the KM2A array has been operating stably since the end of 2019. In this paper, we present the KM2A data analysis pipeline and the first observation of the Crab Nebula, a standard candle in very high energy γ-ray astronomy. We detect γ-ray signals from the Crab Nebula in both energy ranges of 10 100 TeV and 100 TeV with high significance, by analyzing the KM2A data of 136 live days between December 2019 and May 2020. With the observations, we test the detector performance, including angular resolution, pointing accuracy and cosmic-ray background rejection power. The energy spectrum of the Crab Nebula in the energy range 10-250 TeV fits well with a single power-law function dN/dE = (1.13 0.05 0.08 ) 10 (E/20 TeV) cm s TeV . It is consistent with previous measurements by other experiments. This opens a new window of γ-ray astronomy above 0.1 PeV through which new ultrahigh-energy γ-ray phenomena, such as cosmic PeVatrons, might be discovered.

Depositing pinhole-free perovskite films is of vital importance for achieving high performance perovskite solar cells, especially in a planar heterojunction device. Here, perovskite films with coverage approaching 100% and with highly oriented crystal domains were obtained by carefully controlling the annealing temperature and duration. Perovskite solar cells with an average efficiency of 12% and a maximum efficiency of 15.17% were achieved in a planar heterojunction structure. Comprehensive characterization and analysis showed that appropriate annealing temperature and duration allowed the perovskite crystals to grow slowly, resulting in highly oriented crystal domains without any internal voids or pinholes. The anisotropic transport properties of perovskite crystals ensure efficient electron and hole transport to their corresponding electrodes.

Cytomegalovirus infections are an important cause of disease for which no licensed vaccine exists. Recent studies have focused on the gH/gL/UL128-131 complex as antibodies to gH/gL/UL128-131 neutralize viral entry into epithelial cells. Prior studies have used cells from the retinal pigment epithelium, while to prevent transmission, vaccine-induced antibodies may need to block viral infection of epithelial cells of the oral or genital mucosa. We found that gH/gL/UL128-131 is necessary for efficient viral entry into epithelial cells derived from oral and genital mucosa, that short peptides from UL130 and UL131 elicit high titer neutralizing antibodies in rabbits, and that such antibodies neutralize viral entry into epithelial cells derived from these relevant tissues. These results suggest that single subunits or peptides may be sufficient to elicit potent epithelial entry neutralizing responses and that secretory antibodies to such neutralizing epitopes have the potential to provide sterilizing immunity by blocking initial mucosal infection.

In this paper, a neural network (NN)-based online model-free integral reinforcement learning algorithm is developed to solve the finite-horizon optimal tracking control problem for completely unknown nonlinear continuous-time systems with disturbance and saturating actuators (constrained control input). An augmented system is constructed with the tracking error system and the command generator system. A time-varying Hamilton-Jacobi-Isaacs (HJI) equation is formulated for the augmented problem, which is extremely difficult or impossible to solve due to its time-dependent property and nonlinearity. Then, an actor-critic-disturbance NN structure-based scheme is proposed to learn the time-varying solution to the HJI equation in real time without using the knowledge of system dynamics. Since the solution to the HJI equation is time-dependent, the form of NNs representation with constant weights and time-dependent activation functions is considered. Furthermore, an extra error is incorporated in order to satisfy the terminal constraints in the weight update law. Convergence and stability proofs are given based on the Lyapunov theory for nonautonomous systems. Two simulation examples are provided to demonstrate the effectiveness of the designed algorithm.

In this report we describe the genomic sequence of guinea pig cytomegalovirus (GPCMV) assembled from a tissue culture-derived bacterial artificial chromosome clone, plasmid clones of viral restriction fragments, and direct PCR sequencing of viral DNA. The GPCMV genome is 232,678 bp, excluding the terminal repeats, and has a GC content of 55%. A total of 105 open reading frames (ORFs) of > 100 amino acids with sequence and/or positional homology to other CMV ORFs were annotated. Positional and sequence homologs of human cytomegalovirus open reading frames UL23 through UL122 were identified. Homology with other cytomegaloviruses was most prominent in the central ~60% of the genome, with divergence of sequence and lack of conserved homologs at the respective genomic termini. Of interest, the GPCMV genome was found in many cases to bear stronger phylogenetic similarity to primate CMVs than to rodent CMVs. The sequence of GPCMV should facilitate vaccine and pathogenesis studies in this model of congenital CMV infection. FindingsGuinea pig cytomegalovirus (GPCMV) serves as a useful model of congenital infection, due to the ability of the virus to cross the placenta and infect the fetus in utero [1][2][3]. This model is well-suited to vaccine studies for prevention of congenital cytomegalovirus (CMV) infection, a major public health problem and a high-priority area for new vaccine development [4]. However, an impediment to studies in this model has been the lack of detailed DNA sequence data. Although a number of reports have identified specific gene products or clusters of genes [5][6][7][8][9][10][11], to date a full genomic sequence has not been available.We recently reported the construction and preliminary sequence map of a GPCMV bacterial artificial chromosome (BAC) clone maintained in E. coli [12,13], and this clone was used as an initial template for sequence analysis of the full GPCMV genome. BAC DNA was purified using Clontech's NucleoBond ® Plasmid Kits as described previously [14] and both strands were sequenced using an ABI PRISM ® 377 DNA Sequencer, with primers synthesized, as needed, to 'primer-walk' the nucleotide sequence. In parallel, Hind III-and EcoR I-digested fragments were gelpurified and cloned into pUC and pBR322-based vectors as previously described [15]. Plasmid sequences were