New mechanization equations for aided inertial navigation systems

Inertial navigation equations are developed which use area navigation (RNAV) waypoints and runway references as coodinate centers. The formulation is designed for aided inertial navigation systems and gives a high numerical accuracy through all phases of flight. A new formulation of the error equations for inertial navigation systems is also presented. This new formulation reduces numerical calculations in the use of Kalman filters for aided inertial navigation systems

An intracellular traffic jam: Fc receptor-mediated transport of immunoglobulin G

Recent advances in imaging techniques along with more powerful in vitro and in vivo models of receptor-mediated ligand transport are facilitating advances in our understanding of how cells efficiently direct receptors and their cargo to target destinations within the cytoplasm and at the plasma membrane. Specifically, light and 3D electron microscopy studies examining the trafficking behavior of the neonatal Fc receptor (FcRn), a transport receptor for immunoglobulin G (IgG), have given us new insights into the dynamic interplay between the structural components of the cytosolic trafficking machinery, its protein regulators, and the receptors it directs to various locations within the cell. These studies build upon previous biochemical characterizations of FcRn transport and are allowing us to begin formulation of a more complete model for the intracellular trafficking of receptor–ligand complexes

Distinct Intracellular Trafficking Patterns of Host IgG by Herpes Virus Fc-Receptors

Members of both alpha and beta herpes viruses affects 50–98% of people around the world. They cause severe symptoms in congenitally infected newborns, a lifelong latent infection that is lethal in immunocompromised individuals, and are associated with several types of cancer. Human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) viruses express proteins (HCMV gp68 and gp34; HSV-1 gE-gI) that function as Fc receptors (FcRs) by binding to the Fc regions of human IgG. In addition to binding free IgG, these viral FcRs can bind to IgG complexed with an antigen to form an antibody bipolar bridged (ABB) complex. Although HCMV gp68 and HSV-1 gE-gI have an overlapping binding site on Fc, the finding that the gp68/Fc interaction is stable at pH values between 5.6 and 8.1 but that gE-gI binds only at neutral or basic pH suggests distinct pH-based downstream events after IgG is internalized via receptor-mediated endocytosis into intracellular compartments. Here we developed a cell-based in vitro model system to define the fates of ABB complexes formed by the two types of viral FcRs. We found that alpha (HSV-1) and beta (HCMV) herpes virus FcRs displayed distinct intracellular trafficking patterns to target internalized ligands: HSV-1 gE-gI dissociates from its IgG-antigen ligand in acidic endosomal compartments and recycles back to the cell surface, whereas HCMV FcRs (gp68) are transported together with IgG-antigen complexes to lysosomes for degradation. In both cases, anti-viral IgGs and their viral targets are selectively degraded, a potential immune evasion strategy allowing herpes viruses to escape from IgG-mediated immune responses

The Chicken Yolk Sac IgY Receptor, a Functional Equivalent of the Mammalian MHC-Related Fc Receptor, Is a Phospholipase A2 Receptor Homolog

AbstractIn mammals, IgG is transferred from mother to young by the MHC-related receptor FcRn, which binds IgG in acidic endosomes and releases it at basic pH into blood. Maternal IgY, the avian counterpart of IgG, is transferred to embryos across yolk sac membranes. We affinity-purified the chicken yolk sac IgY receptor (FcRY) and sequenced its gene. FcRY is unrelated to MHC molecules but is a homolog of the mammalian phospholipase A2 receptor. Analytical ultracentrifugation and truncation experiments suggest that FcRY forms a compact structure containing an IgY binding site at acidic pH but undergoes a conformational change at basic pH that disrupts the site. FcRY is thus unrelated to mammalian FcRn in both its structure and mechanism for pH-dependent binding, illustrating distinct routes utilized by evolution to transfer antibodies

Ligand Valency Affects Transcytosis, Recycling and Intracellular Trafficking Mediated by the Neonatal Fc Receptor

The neonatal Fc receptor (FcRn) transports IgG across epithelial cell barriers to provide maternal antibodies to offspring and serves as a protection receptor by rescuing endocytosed IgG and albumin from lysosomal degradation. Here we describe the generation of polarized Madin–Darby canine kidney (MDCK) cells expressing rat FcRn (rFcRn) to investigate the potential requirement for ligand bivalency in FcRn-mediated transport. The rFcRn-MDCK cells bind, internalize and bidirectionally transcytose the bivalent ligands IgG and Fc across polarized cell monolayers. However, they cannot be used to study FcRn-mediated transport of the monovalent ligand albumin, as we observe no specific binding, internalization or transcytosis of rat albumin. To address whether ligand bivalency is required for transport, the ability of rFcRn to transcytose and recycle wild-type Fc homodimers (wtFc; two FcRn-binding sites) and a heterodimeric Fc (hdFc; one FcRn-binding site) was compared. We show that ligand bivalency is not required for transcytosis or recycling, but that wtFc is transported more efficiently than hdFc, particularly at lower concentrations. We also demonstrate that hdFc and wtFc have different intracellular fates, with more hdFc than wtFc being trafficked to lysosomes and degraded, suggesting a role for avidity effects in FcRn-mediated IgG transport

Discovery of the magnetic field of the B1/B2V star \sigma Lupi

In our search for new magnetic massive stars we use the strongest indirect indicator of a magnetic field in B stars, which is periodic variability of UV stellar wind lines occurring in a velocity range symmetric around zero. Our aim is to obtain follow-up spectropolarimetry to search for a magnetic field in magnetic candidate stars. We quantify UV wind line variability, and analyse its time behaviour. The B1/B2V star sigma Lup emerged as a new magnetic candidate star. AAT spectropolarimetric measurements with SEMPOL were obtained. The stellar wind line variations of sigma Lup are similar to what is known in magnetic B stars, but no periodicity could be determined. We detected a longitudinal magnetic field with varying strength and amplitude of about 100 G with error bars of typically 20 G, which supports an oblique magnetic-rotator configuration. The equivalent width variations of the UV lines, the magnetic and the optical line variations are consistent with the well-known photometric period of 3.02 days, which we identify with the rotation period of the star. Additional observations with ESPaDOnS at CFHT strongly confirmed this discovery, and allowed to determine a precise magnetic period. Further analysis revealed that $\sigma$ Lupi is a helium-strong star, with an enhanced nitrogen abundance and an underabundance of carbon, and has a spotted surface. We conclude that sigma Lup is a magnetic oblique rotator, and is a He-strong star. It is the 4th B star for which a magnetic field is discovered from studying only its wind variability. Like in the other magnetic B stars the wind emission originates in the magnetic equator, with maximum emission occurring when a magnetic pole points towards the Earth. The 3.02 d magnetic rotation period is consistent with the photometric period, with maximum light corresponding to maximum magnetic field. A full paper will be submitted to A&A.Comment: 4 pages, 5 figures, to appear in proceedings with AIP. Stellar polarimetry: From birth to death, Eds. Jennifer Hoffman, Barb Whitney, and Jon Bjorkma

Asymmetric opening of HIV-1 Env bound to CD4 and a coreceptor-mimicking antibody

The human immunodeficiency virus (HIV-1) envelope (Env) glycoprotein, a (gp120–gp41)₃ trimer, mediates fusion of viral and host cell membranes after gp120 binding to host receptor CD4. Receptor binding triggers conformational changes allowing coreceptor (CCR5) recognition through CCR5’s tyrosine-sulfated amino (N) terminus, release of the gp41 fusion peptide and fusion. We present 3.3 Å and 3.5 Å cryo-EM structures of E51, a tyrosine-sulfated coreceptor-mimicking antibody, complexed with a CD4-bound open HIV-1 native-like Env trimer. Two classes of asymmetric Env interact with E51, revealing tyrosine-sulfated interactions with gp120 mimicking CCR5 interactions, and two conformations of gp120–gp41 protomers (A and B protomers in AAB and ABB trimers) that differ in their degree of CD4-induced trimer opening and induction of changes to the fusion peptide. By integrating the new structural information with previous closed and open envelope trimer structures, we modeled the order of conformational changes on the path to coreceptor binding site exposure and subsequent viral–host cell membrane fusion