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FORMOSAT-7/COSMIC-2 radio occultation (RO) measurements show promise for observing the deep troposphere and for providing critical information on the Earth's planetary boundary layer (PBL). However, refractivity retrieved in the low troposphere can have severe biases under certain thermodynamic conditions. This research examines the characteristics of the deep tropospheric biases and presents methods for estimating the region-dependent refractivity bias using statistical regression models. The results show that the biases have characteristics that vary over land and oceans. With substantial correlation between local spectral width (LSW) and bias, the LSW-based bias estimation model can explain the general pattern of the refractivity bias but with deficiencies in measuring the bias in the ducting regions and in certain areas over land. The estimation model involving the relationship with temperature and specific humidity (TQ) can capture the large biases associated with ducting. Finally, a minimum variance estimation that combines the LSW and TQ provides the most accurate estimation of the refractivity bias.

Abstract We consider the fidelity of the vector meson dominance (VMD) assumption as an instrument for relating the electromagnetic vector-meson production reaction $$e + p \rightarrow e^\prime + V + p$$ e + p → e ′ + V + p to the purely hadronic process $$V + p \rightarrow V+p$$ V + p → V + p . Analyses of the photon vacuum polarisation and the photon-quark vertex reveal that such a VMD Ansatz might be reasonable for light vector-mesons. However, when the vector-mesons are described by momentum-dependent bound-state amplitudes, VMD fails for heavy vector-mesons: it cannot be used reliably to estimate either a photon-to-vector-meson transition strength or the momentum dependence of those integrands that would arise in calculations of the different reaction amplitudes. Consequently, for processes involving heavy mesons, the veracity of both cross-section estimates and conclusions based on the VMD assumption should be reviewed, e.g., those relating to hidden-charm pentaquark production and the origin of the proton mass.

Trigger factor (TF) is a highly conserved multi-domain molecular chaperone that exerts its chaperone activity at the ribosomal tunnel exit from which newly synthesized nascent chains emerge. TF also displays promiscuous substrate binding for a large number of cytosolic proteins independent of ribosome binding. We asked how TF recognizes a variety of substrates while existing in a monomer–dimer equilibrium. Paramagnetic nuclear magnetic resonance (NMR) and electron spin resonance (ESR) spectroscopy were used to show that dimeric TF displays a high degree of structural polymorphism in solution. A series of peptides has been generated to quantify their TF binding affinities in relation with their sequence compositions. The results confirmed a previous predication that TF preferentially binds to peptide fragments that are rich in aromatic and positively charged amino acids. NMR paramagnetic relaxation enhancement analysis showed that TF utilizes multiple binding sites, located in the chaperone domain and part of the prolyl trans–cis isomerization domain, to interact with these peptides. Dimerization of TF effectively sequesters most of the substrate binding sites, which are expected to become accessible upon binding to the ribosome as a monomer. As TF lacks ATPase activity, which is commonly used to trigger conformational changes within molecular chaperones in action, the ribosome-binding-associated disassembly and conformational rearrangements may be the underlying regulatory mechanism of its chaperone activity.

In Holsteins, emerging evidence suggests that long non-coding RNAs (lncRNAs) are actively involved in the regulation of mammary gland development. However, the lncRNA expression pattern in the early growth stage of Holstein mammary gland remains little known. In this study, we comprehensively analyzed 11 mammary gland tissue RNA-Seq datasets derived from Holstein heifer calves (ca. 8 weeks old) retrieved from the Sequence Read Archive database. We identified a total of 588 lncRNAs in the intergenic region. By comparing the sequences with NONCODEv5 database, 241 novel lncRNAs were detected in the mammary gland. Prediction of cis-regulated target gene revealed that 364 out of 588 lncRNAs potentially targeted 417 protein-coding genes. Furthermore, Gene Ontology enrichment determined that potential target genes were mainly involved in the terms associated with energy metabolism and cell differentiation, such as cellular respiration, respiratory electron transport chain, electron transport chain, and regulation of cell differentiation, which were closely related to mammary gland development. This study provides potential candidate lncRNAs in regulating mammary gland development in the early growth stage of Holsteins, as well as a better general understanding of Holstein mammary gland development.

Arctium lappa and A. tomentosum are known medicinal plants in China. The complete chloroplast genomes from A. lappa and A. tomentosum were sequenced using Illumina sequencing technology. The total genome sizes of the complete chloroplast genomes of A. lappa and A. tomentosum were 152 767 bp and 152 688 bp, respectively, and contained a pair of inverted repeats of the same length (15,181 bp). The small single-copies were 18 584 bp and 18 582 bp, and the large single-copies were 83 821 bp and 83 744 bp, respectively. We identified and annotated 134 and 126 genes from A. lappa and A. tomentosum including, respectively, 90 and 89 protein-coding genes, 36 and 29 tRNAs, and eight rRNAs. A. lappa was found to have 10 tRNAs different from those in A. tomentosum, and A. tomentosum had three tRNAs different from those in A. lappa. There were only two types of simple sequence repeats of two species, mononucleotide and dinucleotide, and the sequences were A and T rich. In addition, the two ways of phylogenetic analysis show that the position of A. lappa and A. tomentosum is consistent within Asteraceae.

Phosphoglycerate mutase (PGAM2) catalyzes the conversion of 3-phosphoglycerate into 2-phosphoglycerate and releases energy during glycolysis in muscle tissues. PGAM2 has been considered as a candidate gene to influence growth, development, and carcass traits in livestock. The aim of this study was to investigate the association between polymorphisms of PGAM2 and growth traits in rabbits. Three single nucleotide polymorphisms (SNPs) were identified by direct sequencing in 20 random individuals from three breeds, including c.-10C>T, c.195C>T, and c.414+17C>T. The c.195C>T was genotyped by PCR-RFLP in a total of 222 rabbits of three breeds (Tianfu black, 53 animals; Ira, 91 animals; Champagne, 78 animals). The average allele frequency among the breeds was 0.52 for allele T and 0.48 for C. The heterozygosity and effective number of alleles were 0.4992 and 1.996, respectively. The association results revealed the CT genotype of c.195C>T was associated significantly (P < 0.05) with greater body weight at 84 days of age (BW84) and with average daily weight gain (ADG). However, association of the genotypes with other production traits was not observed. The results of this study suggested PGAM2 is one of the candidate genes affecting BW84 and ADG in the rabbit.

The influence of electron cyclotron wave (ECW) injection with different deposition positions and injection powers on the evolution of peeling–ballooning (P–B) modes is studied with the BOUT++ code, in which the energy deposition and current drive of the ECW are calculated using a ray tracing code. It is shown that the changes in the profiles of plasma pressure, current density, and resistivity induced by ECW injection can significantly influence the linear property and the nonlinear evolution of P–B modes. For the linear simulation, the ECW deposited at the top of the pedestal makes the high toroidal mode number (n) P–B modes more unstable; however, it stabilizes the medium-n to high-n P–B modes when the ECW is deposited at the middle of the pedestal, and the ECW deposited at the bottom of the pedestal decreases the growth rate of P–B modes with medium-n. Further investigation shows that the injected ECW influences the characteristic of linear P–B modes by changing the diamagnetic effect, magnetic shear, pressure gradient, current density, resistivity, and so on. It is known from the nonlinear simulation that the energy loss caused by the edge localized mode (ELM) with ECW injection deposited at the top of the pedestal is nearly the same as that in the case without ECW injection, while the ECW deposited at the middle and bottom of the pedestal is helpful to decrease ELM energy loss. According to the analyses of the time evolution of the P–B mode toroidal spectrum, the physical mechanism of the decrease in ELM energy loss in the simulation is that ECW injection suppresses the most unstable toroidal harmonic of the P–B mode. On the other hand, the influence of ECW injection on P–B modes becomes more obvious when the power of the injected ECW increases. Moreover, the influence of current driven by the ECW on P–B modes is studied separately in this paper, which plays a different role from the bootstrap current.

The temperature effect on the mechanical behavior of the HfNbTaTiZr high entropy alloy (HEA) was investigated at 77–673 K. The decrease of the yield strength with increasing the temperature was mechanistically analyzed by considering contributions from various strengthening mechanisms. An anomalous dependence of strain hardening on temperature was observed and was justified to be caused by dynamic strain aging (DSA) as an extra strengthening mechanism at elevated temperatures. A model was constructed to split the overall strain hardening into forest hardening and DSA hardening, both of which were theoretically quantified at all temperatures considered.

Tumor metastasis into the central nervous system (CNS) and lymph nodes (LNs) is a major obstacle for effective therapies. Therapeutic monoclonal antibodies (mAb) have revolutionized tumor treatment; however, their efficacy for treating metastatic tumors-particularly, CNS and LN metastases-is poor due to inefficient penetration into the CNS and LNs following intravenous injection. We recently reported an effective delivery of mAb to the CNS by encapsulating the anti-CD20 mAb rituximab (RTX) within a thin shell of polymer that contains the analogs of choline and acetylcholine receptors. This encapsulated RTX, denoted as n-RTX, eliminated lymphoma cells systemically in a xenografted humanized mouse model using an immunodeficient mouse as a recipient of human hematopoietic stem/progenitor cells and fetal thymus more effectively than native RTX; importantly, n-RTX showed notable anti-tumor effect on CNS metastases which is unable to show by native RTX. As an important step toward future clinical translation of this technology, we further analyzed the properties of n-RTX in immunocompetent animals, rats, and non-human primates (NHPs). Our results show that a single intravenous injection of n-RTX resulted in 10-fold greater levels in the CNS and 2-3-fold greater levels in the LNs of RTX, respectively, than the injection of native RTX in both rats and NHPs. In addition, we demonstrate the enhanced delivery and efficient B-cell depletion in lymphoid organs of NHPs with n-RTX. Moreover, detailed hematological analysis and liver enzyme activity tests indicate n-RTX treatment is safe in NHPs. As this nanocapsule platform can be universally applied to other therapeutic mAbs, it holds great promise for extending mAb therapy to poorly accessible body compartments.

Based on the magnetic field configuration of the Chinese First Quasi-axisymmetric Stellarator (CFQS) device, three types of orbits such as the passing orbit, blocked trapped orbit, and localized trapped orbit are simulated using the Boris algorithm. Also, the orbital topology, orbit transition, and loss characteristics of these particles under different initial conditions are studied in this paper. It is found that there exists a transition from blocked trapped orbits to localized trapped orbits due to small continuous helical ripples. This phenomenon is analyzed as follows: we define the angle between the particle drift velocity (v→D) and the radial direction (ρ^) as β. If the blocked-localized transition appears in the region where β>90○, the localized particles will return to the blocked particles and be constrained. However, if the blocked-localized transition happens in the region where β

Interfacial properties between metal back contacts and solar cell absorbers play important roles in determining efficiencies, but studies of such properties in CZTS and CZTSe based solar cells are quite lacking from theoretical aspects. To fill such a blank and explore insights for improving energy conversion efficiencies, we have studied interfacial properties in CZTS and CZTSe solar cells. The natural band offsets between CZTX and the spontaneously formed MoX2 layer (X = S, Se) are obtained using our recently developed intermediate-phase method. We find that the band alignment between CZTS and MoS2 is actually harmful while the band alignment between CZTSe and MoSe2 is beneficial for carrier extractions. We further propose to engineer the back contact interface to improve CZTS solar cell efficiency by depositing a thin layer of Se on the Mo back contact prior to the CZTS deposition, thus avoiding the formation of the undesirable MoS2 layer.

In a recent clone-tracking experiment, millions of uniquely tagged hematopoietic stem cells (HSCs) and progenitor cells were autologously transplanted into rhesus macaques and peripheral blood containing thousands of tags were sampled and sequenced over 14 years to quantify the abundance of hundreds to thousands of tags or "clones." Two major puzzles of the data have been observed: consistent differences and massive temporal fluctuations of clone populations. The large sample-to-sample variability can lead clones to occasionally go "extinct" but "resurrect" themselves in subsequent samples. Although heterogeneity in HSC differentiation rates, potentially due to tagging, and random sampling of the animals' blood and cellular demographic stochasticity might be invoked to explain these features, we show that random sampling cannot explain the magnitude of the temporal fluctuations. Moreover, we show through simpler neutral mechanistic and statistical models of hematopoiesis of tagged cells that a broad distribution in clone sizes can arise from stochastic HSC self-renewal instead of tag-induced heterogeneity. The very large clone population fluctuations that often lead to extinctions and resurrections can be naturally explained by a generation-limited proliferation constraint on the progenitor cells. This constraint leads to bursty cell population dynamics underlying the large temporal fluctuations. We analyzed experimental clone abundance data using a new statistic that counts clonal disappearances and provided least-squares estimates of two key model parameters in our model, the total HSC differentiation rate and the maximum number of progenitor-cell divisions.

A novel approach for positron injection and acceleration in the laser driven plasma wakefield is proposed. One ring-shaped beam and one coaxially propagating Gaussian beam drive wakefields in a preformed plasma volume filled with both electrons and positrons. The laser’s ponderomotive force as well as the charge separation force in the front bucket of the first bubble are utilized to provide the transverse momenta of injected positrons and those positrons can be trapped by the focusing field and then accelerated by the wakefield. Theoretical analysis of the process is presented and verified by particle-in-cell simulations. The simulations show that relatively high-charge, quasimonoenergetic positron beams can be obtained.

[This corrects the article DOI: 10.1371/journal.ppat.1006753.].

Chimeric Antigen Receptor (CAR) T-cells have emerged as a powerful immunotherapy for various forms of cancer and show promise in treating HIV-1 infection. However, significant limitations are persistence and whether peripheral T cell-based products can respond to malignant or infected cells that may reappear months or years after treatment remains unclear. Hematopoietic Stem/Progenitor Cells (HSPCs) are capable of long-term engraftment and have the potential to overcome these limitations. Here, we report the use of a protective CD4 chimeric antigen receptor (C46CD4CAR) to redirect HSPC-derived T-cells against simian/human immunodeficiency virus (SHIV) infection in pigtail macaques. CAR-containing cells persisted for more than 2 years without any measurable toxicity and were capable of multilineage engraftment. Combination antiretroviral therapy (cART) treatment followed by cART withdrawal resulted in lower viral rebound in CAR animals relative to controls, and demonstrated an immune memory-like response. We found CAR-expressing cells in multiple lymphoid tissues, decreased tissue-associated SHIV RNA levels, and substantially higher CD4/CD8 ratios in the gut as compared to controls. These results show that HSPC-derived CAR T-cells are capable of long-term engraftment and immune surveillance. This study demonstrates for the first time the safety and feasibility of HSPC-based CAR therapy in a large animal preclinical model.

Cellular retinol-binding protein II (CRBP II) belongs to the family of cellular retinol-binding proteins and plays a major role in absorption, transport, and metabolism of vitamin A. In addition, because vitamin A is correlated with reproductive performance, we measured CRBP II mRNA abundance in erlang mountainous chickens by real-time PCR using the relative quantification method. The expression of CRBP II showed a tissue-specific pattern and egg production rate-dependent changes. The expression was very high (p

Anti-retroviral drugs suppress HIV-1 plasma viremia to undetectable levels; however, latent HIV-1 persists in reservoirs within HIV-1-infected patients. The silent provirus can be activated through the use of drugs, including protein kinase C activators and histone deacetylase inhibitors. This "shock" approach is then followed by "kill" of the producing cells either through direct HIV-1-induced cell death or natural immune mechanisms. However, these mechanisms are relatively slow and effectiveness is unclear. Here, we develop an approach to specifically target and kill cells that are activated early in the process of virus production. We utilize a novel nanocapsule technology whereby the ricin A chain is encapsulated in an inactive form within a polymer shell. Specificity for release of the ricin A toxin is conferred by peptide crosslinkers that are sensitive to cleavage by HIV-1 protease. By using well-established latent infection models, J-Lat and U1 cells, we demonstrate that only within an HIV-1-producing cell expressing functional HIV-1 protease will the nanocapsule release its ricin A cargo, shutting down viral and cellular protein synthesis, and ultimately leading to rapid death of the producer cell. Thus, we provide proof of principle for a novel technology to kill HIV-1-producing cells without effects on non-target cells.