No countermeasures currently exist for the prevention or treatment of the severe sequelae of Filovirus (such as Ebola virus; EBOV) infection. To overcome this limitation in our biodefense preparedness, we have designed monoclonal antibodies (mAbs) which could be used in humans as immunoprotectants for EBOV, starting with a murine mAb (13F6) that recognizes the heavily glycosylated mucin-like domain of the virion-attached glycoprotein (GP). Point mutations were introduced into the variable region of the murine mAb to remove predicted human T-cell epitopes, and the variable regions joined to human constant regions to generate a mAb (h-13F6) appropriate for development for human use. We have evaluated the efficacy of three variants of h-13F6 carrying different glycosylation patterns in a lethal mouse EBOV challenge model. The pattern of glycosylation of the various mAbs was found to correlate to level of protection, with aglycosylated h-13F6 providing the least potent efficacy (ED 50 = 33 μg). A version with typical heterogenous mammalian glycoforms (ED 50 = 11 μg) had similar potency to the original murine mAb. However, h-13F6 carrying complex N-glycosylation lacking core fucose exhibited superior potency (ED 50 = 3 μg). Binding studies using Fcγ receptors revealed enhanced binding of nonfucosylated h-13F6 to mouse and human FcγRIII. Together the results indicate the presence of Fc N-glycans enhances the protective efficacy of h-13F6, and that mAbs manufactured with uniform glycosylation and a higher potency glycoform offer promise as biodefense therapeutics.passive immunization | antibody glycosylation | antibody-dependent cellular cytotoxicity | antiviral

Clear cell, papillary, and chromophobe RCCs demonstrate different patterns of enhancement on two-time point clinical dynamic contrast-enhanced MR images, allowing their differentiation with high sensitivity and specificity.

The sodium concentration gradient in the kidney (from the cortex to the medulla) serves to regulate fluid homeostasis and is tightly coupled to renal function. It was previously shown that renal function and pathophysiology can be characterized in rat kidneys by measuring the sodium gradient with 23 Na MRI. This study demonstrates for the first time the ability of 23 Na MRI to map the distribution of sodium in the human kidney and to quantify the corticomedullary sodium gradient. The study was performed on a 3T Signa LX scanner (GE) using an in-house-built quadrature surface coil.

Residual oil fly ash (ROFA) is a chemically complex mixture of compounds, including metals that are potentially carcinogenic because of their ability to cause oxidative injury. In this study, we investigated the association between exposure to particulate matter with an aerodynamic mass median diameter