A viable mouse model of factor X deficiency provides evidence for maternal transfer of factor X.

BackgroundActivated factor X (FXa) is a vitamin K-dependent serine protease that plays a pivotal role in blood coagulation by converting prothrombin to thrombin. There are no reports of humans with complete deficiency of FX, and knockout of murine F10 is embryonic or perinatal lethal.ObjectiveWe sought to generate a viable mouse model of FX deficiency.MethodsWe used a socket-targeting construct to generate F10-knockout mice by eliminating F10 exon 8 (knockout allele termed F10(tm1Ccmt), abbreviated as '-'; wild-type '+'), and a plug-targeting construct to generate mice expressing a FX variant with normal antigen levels but low levels of FX activity [4-9% normal in humans carrying the defect, Pro343-->Ser, termed FX Friuli (mutant allele termed F10(tm2Ccmt), abbreviated as F)].ResultsF10 knockout mice exhibited embryonic or perinatal lethality. In contrast, homozygous Friuli mice [F10 (F/F)] had FX activity levels of approximately 5.5% (sufficient to rescue both embryonic and perinatal lethality), but developed age-dependent iron deposition and cardiac fibrosis. Interestingly, F10 (-/F) mice with FX activity levels of 1-3% also showed complete rescue of lethality. Further study of this model provides evidence supporting a role of maternal FX transfer in the embryonic survival.ConclusionsWe demonstrate that, while complete absence of FX is incompatible with murine survival, minimal FX activity as low as 1-3% is sufficient to rescue the lethal phenotype. This viable low-FX mouse model will facilitate the development of FX-directed therapies as well as investigation of the FX role in embryonic development

Extensive winter subglacial water storage beneath the Greenland Ice Sheet

This is the final version of the article. Available from AGU via the DOI in this record.Surface meltwater that reaches the base of the Greenland Ice Sheet exerts a fundamental impact on ice flow, but observations of catchment-wide movement and distribution of subglacial water remain limited. Using radar-sounding data from two seasons, we identify the seasonal distribution of subglacial water in western Greenland. Our analysis provides evidence of widespread subglacial water storage beneath Greenland in the wintertime. The winter storage is located primarily on bedrock ridges with higher bed elevations in excess of 200 m. During the melt season water moves to the subglacial troughs. This inverse relationship with topography indicates that the material properties of the glacier bed strongly influence subglacial drainage development. Both the spatial variations in bed properties and the initial state of the subglacial hydrology system at the start of the melt season lead to differing glacier dynamical responses to surface melting across the Greenland Ice Sheet.W.C. is a recipient of the NASA Earth and Space Science Fellowship. D.M.S. is supported by a grant from the NASA Cryospheric Sciences Program. H.S. is supported by grants from the NASA Cryospheric Sciences and Sea Level Rise Programs. T.T.C and R.E.B are supported by grants from National Science Foundation (NSF) and NASA Cryospheric Sciences. S.P. is supported by the Natural Environment Research Council’s Centre for Polar Observatio

Gauge and Supersymmetric Invariance of a Boundary Bagger-Lambert-Gustavsson Theory

In this paper we will discuss the effect of a having a boundary on the supersymmetric invariance and gauge invariance of the Bagger-Lambert-Gustavsson (BLG) Theory. We will show that even though the supersymmetry and gauge invariance of the original BLG theory is broken due to the presence of a boundary, it restored by the addition of suitable boundary terms. In fact, to achieve the gauge invariance of this theory, we will have to introduce new boundary degrees of freedom. The boundary theory obeyed by these new boundary degrees of freedom will be shown to be a generalization of the gauged Wess-Zumino-Witten model, with the generators of the Lie algebra replaced by the generators of the Lie 3-algebra. The gauge and supersymmetry variations of the boundary theory will exactly cancel the boundary terms generated by the gauge and supersymmetric variations of the bulk theory.Comment: 15 pages, 0 figures, accepted for publication in JHE

Sustained response after a 2-year course of lamivudine treatment of hepatitis B e antigen-negative chronic hepatitis B

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72882/1/j.1365-2893.2004.00556.x.pd

Possible scale invariant linear magnetoresistance in pyrochlore iridates Bi2Ir2O7

We report the observation of a linear magnetoresistance in single crystals and epitaxial thin films of the pyrochlore iridate Bi2Ir2O7. The linear magnetoresistance is positive and isotropic at low temperatures, without any sign of saturation up to 35 T. As temperature increases, the linear field dependence gradually evolves to a quadratic field dependence. The temperature and field dependence of magnetoresistance of Bi2Ir2O7 bears strikingly resemblance to the scale invariant magnetoresistance observed in the strange metal phase in high Tc cuprates. However, the residual resistivity of Bi2Ir2O7 is more than two orders of magnitude higher than the curpates. Our results suggest that the correlation between linear magnetoresistance and quantum fluctuations may exist beyond high temperature superconductors

D=3, N=8 conformal supergravity and the Dragon window

We give a superspace description of D=3, N=8 supergravity. The formulation is off-shell in the sense that the equations of motion are not implied by the superspace constraints (but an action principle is not given). The multiplet structure is unconventional, which we connect to the existence of a "Dragon window", that is modules occurring in the supercurvature but not in the supertorsion. According to Dragon's theorem this cannot happen above three dimensions. We clarify the relevance of this window for going on the conformal shell, and discuss some aspects of coupling to conformal matter.Comment: plain tex, 24 pp v2: minor change

Classification of facial periâ implant soft tissue dehiscence/deficiencies at single implant sites in the esthetic zone

BackgroundThe incidence of a periâ implant soft tissue dehiscence/deficiency (PSTD) is not a rare finding. Despite multiple previous attempts aimed at correcting the PSTDs, a classification of these conditions has not yet been proposed. This lack in the literature may also lead to discrepancies in the reported treatment outcomes and thus misinform the clinician or the readers. The aim of the present article was therefore to present a classification of periâ implant PSTD at a single implant site.MethodsFour classes of PSTDs were discussed based on the position of the gingival margin of the implantâ supported crown in relation to the homologous natural tooth. In addition, the buccoâ lingual position of the implant head was also taken into consideration. Each class was further subdivided based on the height of the anatomical papillae.ResultsSubsequently, for each respective category a surgical approach (including bilaminar techniques, the combined prostheticâ surgical approach or soft tissue augmentation with a submerged healing) was also suggested.ConclusionThis paper provides a new classification system for describing PSTDs at single implant sites, with the appropriate recommended treatment protocol.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151905/1/jper10351_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151905/2/jper10351.pd

Lead-free piezoelectric K0.5Bi0.5TiO3–Bi(Mg0.5Ti0.5)O3 ceramics with depolarisation temperatures up to ~220 C

The properties of K0.5Bi0.5TiO3-rich ceramic solid solutions in the system (1 - x)K0.5Bi0.5TiO3– xBi(Mg0.5Ti0.5)O3 are reported. The highest values of piezoelectric charge coefficient, d33, and field-induced strains are found in compositions located close to a compositional boundary between single-phase tetragonal and mixed tetragonal ? cubic perovskite phases. Maximum d33 values were *150 pC/N for x = 0.03, with positive strains of *0.25 %; the x = 0.04 composition had a d33 * 133 pC/N and strain of 0.35 % (bipolar electric field, 50 kV/ cm, 1 Hz). Depolarisation temperature Td is an important selection criterion for any lead-free piezoelectric for actuator or sensor applications. A Td of *220 C for x = 0.03 is *100 C higher than for the widely reported Na0.5Bi0.5TiO3–BaTiO3 system, yet d33 values and strains are similar, suggesting the new material is worthy of further attention as a lead-free piezoceramic for elevated temperature applications