Envelope addressed to Mr. Welland D. Woodruff from Caldwell, Masslich and Reed, Attorneys and Counsellors at Law

Envelope addressed to Mr. Welland D. Woodruff from Caldwell, Masslich and Reed, Attorneys and Counsellors at Law, New York, postmarked Hudson Terminal Station, New York, June 17, 1913.

Envelope addressed to Mr. Welland D. Woodruff from Caldwell, Masslich and Reed

Envelope addressed to Mr. Welland D. Woodruff from Caldwell, Masslich and Reed, Attorneys and Counsellors at Law, New York, postmarked Hudson Terminal Station, New York, Sept. 23, 1913.

Envelope addressed to Mr. Welland D. Woodruff from Caldwell, Masslich and Reed, Attorneys and Counsellors at Law

Envelope addressed to Mr. Welland D. Woodruff from Caldwell, Masslich and Reed, Attorneys and Counsellors at Law, New York, postmarked Hudson Terminal Station, New York, Sept. 22, 1913.

Envelope (partial) to Colonel Nelles, 4th Lincoln Militia, Grimsby from M.A. Hale of Quebec

Envelope (partial) to Colonel Nelles, 4th Lincoln Militia, Grimsby from M.A. Hale of Quebec. The envelope is stained and torn, but text is not affected, Feb. 7, 1839.

Envelope addressed to Mrs. Henry H. Nelles of St. Catharines

Envelope addressed to Mrs. Henry H. Nelles of St. Catharines. The envelope is postmarked U.S. and St. Catharines. There is no return address, April 1859.

Methods of generating carrier-envelope-phase stabilized, intense, few-cycle laser pulses

Ultrafast laser pulses have become an integral part of the toolbox of countless laboratories doing physics, chemistry, and biological research. The work presented here is motivated by a section in the ever-growing, interdisciplinary research towards understanding the fundamental workings of light-matter interactions. Specifically, attosecond pulses can be useful tools to obtain the desired insight. However access to, and the utility of, such pulses is dependent on the generation of intense, few-cycle, carrier-envelope-phase stabilized laser pulses. The presented work can be thought of as a sort of roadmap towards the latter. From the oscillator which provides the broadband seed to amplification methods, the integral pieces necessary for the generation of attosecond pulses are discussed. A range of topics from the fundamentals to design challenges is presented, outfitting the way towards the practical implementation of an intense few-cycle carrier-envelope-phase stabilized laser source.

Iron-regulated surface determinant protein a mediates adhesion of staphylococcus aureus to human corneocyte envelope proteins

The ability of Staphylococcus aureus to colonize the human nares is a crucial prerequisite for disease. IsdA is a major S. aureus surface protein that is expressed during human infection and required for nasal colonization and survival on human skin. In this work, we show that IsdA binds to involucrin, loricrin, and cytokeratin K10, proteins that are present in the cornified envelope of human desquamated epithelial cells. To measure the forces and dynamics of the interaction between IsdA and loricrin (the most abundant protein of the cornified envelope), single-molecule force spectroscopy was used, demonstrating high-specificity binding. IsdA acts as a cellular adhesin to the human ligands, promoting whole-cell binding to immobilized proteins, even in the absence of other S. aureus components (as shown by heterologous expression in Lactococcus lactis). Inhibition experiments revealed the binding of the human ligands to the same IsdA region. This region was mapped to the NEAT domain of IsdA. The NEAT domain also was found to be required for S. aureus whole-cell binding to the ligands as well as to human nasal cells. Thus, IsdA is an important adhesin to human ligands, which predominate in its primary ecological niche.

Contribution of redox status to hepatitis C virus E2 envelope protein function and antigenicity

Disulfide bonding contributes to the function and antigenicity of many viral envelope glycoproteins. We assessed here its significance for the hepatitis C virus E2 envelope protein and a counterpart deleted for hypervariable region-1 (HVR1). All 18 cysteine residues of the antigens were involved in disulfides. Chemical reduction of up to half of these disulfides was compatible with anti-E2 monoclonal antibody reaction, CD81 receptor binding, and viral entry, whereas complete reduction abrogated these properties. The addition of 5,5'-dithiobis-2-nitrobenzoic acid had no effect on viral entry. Thus, E2 function is only weakly dependent on its redox status, and cell entry does not require redox catalysts, in contrast to a number of enveloped viruses. Because E2 is a major neutralizing antibody target, we examined the effect of disulfide bonding on E2 antigenicity. We show that reduction of three disulfides, as well as deletion of HVR1, improved antibody binding for half of the patient sera tested, whereas it had no effect on the remainder. Small scale immunization of mice with reduced E2 antigens greatly improved serum reactivity with reduced forms of E2 when compared with immunization using native E2, whereas deletion of HVR1 only marginally affected the ability of the serum to bind the redox intermediates. Immunization with reduced E2 also showed an improved neutralizing antibody response, suggesting that potential epitopes are masked on the disulfide-bonded antigen and that mild reduction may increase the breadth of the antibody response. Although E2 function is surprisingly independent of its redox status, its disulfide bonds mask antigenic domains. E2 redox manipulation may contribute to improved vaccine design.