Adam Finnefrock - Profile on Academia.edu (original) (raw)
Papers by Adam Finnefrock
Dynamic scaling during CDW relaxation from the sliding state
Journal de physique, Dec 1, 1999
ABSTRACT Using time-resolved high-resolution x-ray scattering techniques, we have measured the ev... more ABSTRACT Using time-resolved high-resolution x-ray scattering techniques, we have measured the evolution of the structure of the Q1 charge-density wave in NbSe3 as it relaxes after an applied electric field is turned off. Measurements were made at temperatures between 70 and 120 K and at applied field strengths up to 40x the threshold for sliding. These time-dependent structural data are accurately described by dynamic scaling theory. For threshold field strengths less than the threshold to sliding, the value of the dynamic scaling exponent µ is consistent with the value predicted by assuming that the CDW is an elastic medium. However, for field strengths greater than threshold, µ is significantly smaller, indicating that phase-slip (amplitude fluctuations) is (are) necessary for a correct physical description.
Pigment Analysis of a Landscape by Gustave Courbet
University of Pennsylvania Press, Inc. eBooks, Feb 14, 2023
arXiv: Materials Science, 2019
A major motivation for the scientific study of artworks is to understand their states of preserva... more A major motivation for the scientific study of artworks is to understand their states of preservation and ongoing degradation mechanisms. This enables preservation strategies to be developed for irreplaceable works. Intensely-hued cadmium sulphide (CdS) yellow pigments are of particular interest because these are key to the palettes of many important late 19th and early 20th century masters, including Vincent Van Gogh, Pablo Picasso, Henri Matisse, and Edvard Munch. As these paintings age, their cadmium yellow paints are undergoing severe fading, flaking, and discolouration. These effects are associated with photodegradation, the light-facilitated reactions of CdS with oxygen, moisture, and even the paint binding medium. The use of common optical and X-ray methods to characterize the physical state of the pigment is challenging due to the mixing of the various components of the paint at length scales smaller than their resolution. Here, we present an atomic-scale structural and chem...
Evaluation of HCMV vaccines in rhesus macaques by a novel micro-neutralization assay (113.4)
Journal of Immunology, May 1, 2012
Human cytogemalovirus (HCMV) causes wide-spread infection in adult human populations. Although no... more Human cytogemalovirus (HCMV) causes wide-spread infection in adult human populations. Although no symptoms observed in healthy persons, HCMV infection can cause severe and even life-threatening diseases in immune-compromised individuals. There are lines of evidence that humoral immunity can provide protection against HCMV infection. We have tested several versions of HCMV vaccines based on laboratory strain AD169 with its epithelial tropism restored in rhesus macaques. Vaccines were administered intramuscularly three times. In comparison, recombinant HCMV gB protein vaccine, which showed marginal protections in previous clinical trial, was given with adjuvant MF59. To facilitate the evaluation of these vaccines, we have developed a novel micro-neutralization assay based on the detection of a dominant HCMV antigen expressed in ARPE19 cells, using near infrared dye-labeled immune reagents, to measure HCMV neutralizing activities in serum samples of vaccinated monkeys. Our results showed that AD169 revertant vaccines induced much stronger neutralizing activities than recombinant gB vaccine in rhesus monkeys. The addition of ISCOMATRIX adjuvant (CSL, Ltd) in the vaccine formulation further enhanced its immunogenicity. There were significant boost effects after the second injection, while the third injection did not increase the neutralizing titers above those obtained post the second vaccination.
Journal of Immunological Methods, Feb 1, 2013
This paper describes an approach to surface plasmon resonance (SPR) based epitope mapping, also r... more This paper describes an approach to surface plasmon resonance (SPR) based epitope mapping, also referred to as pairwise antibody footprinting, involving the direct immobilization of an antigen-specific primary mAb to the surface of an SPR interface. This technique offers a more straightforward approach than indirect capture (e.g., via rabbit anti-mouse Fc) as it does not require additional steps to block the unoccupied immobilized anti-Fc to prevent non-specific antibody binding. This is also an alternative to the direct immobilization of an antigen of interest, which may cause conformational changes in the antigen or epitope degradation upon chemical immobilization, particularly in successive regeneration cycles. It is particularly suitable for highly multivalent targets such as virus-like particles (VLPs). Using this technique, we assessed a panel of eight monoclonal antibodies against HPV (human papilloma virus) L1 protein VLPs expressed by Saccharomyces cerevisiae. In the antibody epitope screening studies, HPV16 L1-directed conformational mAbs were clearly distinguished from the linear mAbs and consistent with known epitope information. Additional studies using a linear mAb and a conformational mAb demonstrate the practical application of this technique for characterizing the result of process changes and the consistency of recombinant HPV16 VLPs. The method is readily extensible to other VLPs and VLP-based vaccines.
Clinical and Vaccine Immunology, Aug 1, 2009
In an effort to characterize important epitopes of Staphylococcus aureus iron-regulated surface d... more In an effort to characterize important epitopes of Staphylococcus aureus iron-regulated surface determinant B (IsdB), murine IsdB-specific monoclonal antibodies (MAbs) were isolated and characterized. A panel of 12 MAbs was isolated. All 12 MAbs recognized IsdB in enzyme-linked immunosorbent assays and Western blots; 10 recognized native IsdB expressed by S. aureus. The antigen epitope binding of eight of the MAbs was examined further. Three methods were used to assess binding diversity: MAb binding to IsdB muteins, pairwise binding to recombinant IsdB, and pairwise binding to IsdB-expressing bacteria. Data from these analyses indicated that MAbs could be grouped based on distinct or nonoverlapping epitope recognition. Also, MAb binding to recombinant IsdB required a significant portion of intact antigen, implying conformational epitope recognition. Four MAbs with nonoverlapping epitopes were evaluated for in vitro opsonophagocytic killing (OPK) activity and efficacy in murine challenge models. These were isotype switched from immunoglobulin G1 (IgG1) to IgG2b to potentially enhance activity; however, this isotype switch did not appear to enhance functional activity. MAb 2H2 exhibited OPK activity (>50% killing in the in vitro OPK assay) and was protective in two lethal challenge models and a sublethal indwelling catheter model. MAb 13C7 did not exhibit OPK (<50% killing in the in vitro assay) and was protective in one lethal challenge model. Neither MAb 13G11 nor MAb 1G3 exhibited OPK activity in vitro or was active in a lethal challenge model. The data suggest that several nonoverlapping epitopes are recognized by the IsdB-specific MAbs, but not all of these epitopes induce protective antibodies.
Clinical and Vaccine Immunology, Apr 1, 2014
Human papillomavirus (HPV) is the etiological agent for all cervical cancers, a significant numbe... more Human papillomavirus (HPV) is the etiological agent for all cervical cancers, a significant number of other anogenital cancers, and a growing number of head and neck cancers. Two licensed vaccines offer protection against the most prevalent oncogenic types, 16 and 18, responsible for approximately 70% of cervical cancer cases worldwide and one of these also offers protection against types 6 and 11, responsible for 90% of genital warts. The vaccines are comprised of recombinantly expressed major capsid proteins that self-assemble into virus-like particles (VLPs) and prevent infection by eliciting neutralizing antibodies. Adding the other frequently identified oncogenic types 31, 33, 45, 52, and 58 to a vaccine would increase the coverage against HPV-induced cancers to approximately 90%. We describe the generation and characterization of panels of monoclonal antibodies to these five additional oncogenic HPV types, and the selection of antibody pairs that were high affinity and type specific and recognized conformation-dependent neutralizing epitopes. Such characteristics make these antibodies useful tools for monitoring the production and potency of a prototype vaccine as well as monitoring vaccine-induced immune responses in the clinic.
A fully human monoclonal antibody to Staphylococcus aureus iron regulated surface determinant B (IsdB) with functional activity in vitro and in vivo
Human antibodies, Dec 15, 2010
Nucleation in Submonolayer Electrodeposition
APS, Mar 1, 1998
ABSTRACT We have studied phin situ the ordering of a two-dimensional CuCl crystal electrodeposite... more ABSTRACT We have studied phin situ the ordering of a two-dimensional CuCl crystal electrodeposited on a Pt(111) surface. We simultaneously measured high-resolution time-resolved x-ray scattering and chronoamperometric transients. Both measurements were synchronized with the leading edge of an applied potential step which stimulated the desorption of Cu and subsequent ordering of the CuCl crystal. In all cases, the current transient occurs on a shorter time-scale than the development of crystalline order. The scattered x-ray intensity data (2 × 10^4 data points) vs. time and transverse momentum transfer can be fit to an Avrami-like function with only three parameters. By performing a series of voltage-step experiments, we demonstrate that the ordering time diverges with applied potential phi as tau ~ exp [ 1 / (phi - phi_0) ], consistent with the nucleation and growth of two-dimensional clusters. Monitoring the time-dependent widths of the x-ray peak, we see a narrowing corresponding to the growing clusters. Further information is available at http://www.msc.cornell.edu/ adam
Research paper Design and optimization of a multiplex anti-influenza peptide immunoassay
Scientific Study, Condition Challenges, and Attribution Questions in Yves Tanguy’s Oeuvre
Cultural heritage science, 2022
Proceedings of the National Academy of Sciences of the United States of America, Jan 17, 2013
Human cytomegalovirus (HCMV) can cause serious morbidity/mortality in transplant patients, and co... more Human cytomegalovirus (HCMV) can cause serious morbidity/mortality in transplant patients, and congenital HCMV infection can lead to birth defects. Developing an effective HCMV vaccine is a high medical priority. One of the challenges to the efforts has been our limited understanding of the viral antigens important for protective antibodies. Receptor-mediated viral entry to endothelial/epithelial cells requires a glycoprotein H (gH) complex comprising five viral proteins (gH, gL, UL128, UL130, and UL131). This gH complex is notably missing from HCMV laboratory strains as well as HCMV vaccines previously evaluated in the clinic. To support a unique vaccine concept based on the pentameric gH complex, we established a panel of 45 monoclonal antibodies (mAbs) from a rabbit immunized with an experimental vaccine virus in which the expression of the pentameric gH complex was restored. Over one-half (25 of 45) of the mAbs have neutralizing activity. Interestingly, affinity for an antibody ...
mAbs, 2009
The human D5 monoclonal antibody binds to the highly conserved hydrophobic pocket on the N-termin... more The human D5 monoclonal antibody binds to the highly conserved hydrophobic pocket on the N-terminal heptad repeat (NHR) trimer of HIV-1 gp41 and exhibits modest yet relatively broad neutralization activity. Both binding and neutralization depend on residues in the complementarity determining regions (CDRs) of the D5 IgG variable domains on heavy chain (VH) and light chain (VL). In an effort to increase neutralization activity to a wider range of HIV-1 strains, we have affinity matured the parental D5 scFv by randomizing selected residues in 5 of its 6 CDRs. The resulting scFv variants derived from four different CDR changes showed enhanced binding affinities to gp41 NHR mimetic (5-helix) which correlated to improved neutralization potencies by up to 8-fold. However, when converted to IgG1s, these D5 variants had up to a 12-fold reduction in neutralization potency over their corresponding scFvs despite their slightly enhanced in vitro binding affinities. Remarkably, D5 variant IgG1s bearing residue changes in CDRs that interact with epitope residues N-terminal to the hydrophobic pocket (such as VH CDR3 and VL CDR3) retained more neutralization potency than those containing residue changes in pocketinteracting CDRs (such as VH CDR2). These results provide compelling evidence for the existence of a steric block to an IgG that extends to the gp41 NHR hydrophobic pocket region, and can be a useful guide for developing therapeutic antibodies and vaccines circumventing this block.
Clinical and Vaccine Immunology, 2014
ABSTRACTHuman papillomavirus (HPV) is the etiological agent for all cervical cancers, a significa... more ABSTRACTHuman papillomavirus (HPV) is the etiological agent for all cervical cancers, a significant number of other anogenital cancers, and a growing number of head and neck cancers. Two licensed vaccines offer protection against the most prevalent oncogenic types, 16 and 18, responsible for approximately 70% of cervical cancer cases worldwide and one of these also offers protection against types 6 and 11, responsible for 90% of genital warts. The vaccines are comprised of recombinantly expressed major capsid proteins that self-assemble into virus-like particles (VLPs) and prevent infection by eliciting neutralizing antibodies. Adding the other frequently identified oncogenic types 31, 33, 45, 52, and 58 to a vaccine would increase the coverage against HPV-induced cancers to approximately 90%. We describe the generation and characterization of panels of monoclonal antibodies to these five additional oncogenic HPV types, and the selection of antibody pairs that were high affinity and...
Angewandte Chemie International Edition, 2001
We also acknowledge very helpful discussions with G. E. S. Toombes. details of the SAXS data trea... more We also acknowledge very helpful discussions with G. E. S. Toombes. details of the SAXS data treatment and analysis.)
A fully human monoclonal antibody to Staphylococcus aureus iron regulated surface determinant B (IsdB) with functional activity in vitro and in vivo
Human Antibodies, 2010
A fully human monoclonal antibody (CS-D7, IgG1) specific for the iron regulated surface determina... more A fully human monoclonal antibody (CS-D7, IgG1) specific for the iron regulated surface determinant B (IsdB) of Staphylococcus aureus was isolated from the Cambridge Antibody Technology (CAT) scFv antibody library. As compared to previously described IsdB specific murine monoclonals, CS-D7 has a unique, non-overlapping binding site on IsdB, and exhibits increased in vivo activity. The antibody recognizes a conformational epitope spanning amino acids 50 to 285 and has a binding affinity of 340 (± 75) pM for IsdB. CS-D7 bound to a wide variety of S. aureus strains, but not to an isdB deletion mutant. The antibody mediated opsonophagocytic (OP) killing in vitro and mediated significant protection in vivo. In a murine lethal sepsis model, the antibody conferred protection from death when dosed prior to challenge, but not when dosed after challenge. Importantly, in a central venous catheter (CVC) model in rats, the antibody reduced bacteremia and prevented colonization of indwelling catheters. Protection was observed when rats were dosed with CS-D7 prior to challenge as well as post challenge. IsdB is currently being investigated for clinical efficacy against S. aureus infection, and the activity of this human IsdB specific antibody supplements the growing body of evidence to support targeting this antigen for vaccine development.
towards Less-Conserved Regions and Potential Impact on Vaccine Efficacy in the Step Study
T cell directed HIV vaccines are based upon the induction of CD8+ T cell memory responses that wo... more T cell directed HIV vaccines are based upon the induction of CD8+ T cell memory responses that would be effective in inhibiting infection and subsequent replication of an infecting HIV-1 strain, a process that requires a match or near-match between the epitope induced by vaccination and the infecting viral strain. We compared the frequency and specificity of the CTL epitope responses elicited by the replication-defective Ad5 gag/pol/nef vaccine used in the Step trial with the likelihood of encountering those epitopes among recently sequenced Clade B isolates of HIV-1. Among vaccinees with detectable 15-mer peptide pool ELISpot responses, there was a median of four (one Gag, one Nef and two Pol) CD8 epitopes per vaccinee detected by 9-mer peptide ELISpot assay. Importantly, frequency analysis of the mapped epitopes indicated that there was a significant skewing of the T cell response; variable epitopes were detected more frequently than would be expected from an unbiased sampling of ...
Sliding charge-density waves as rough growth surfaces
ABSTRACT Using high-resolution x-ray scattering techniques we have measured the transverse struct... more ABSTRACT Using high-resolution x-ray scattering techniques we have measured the transverse structure of the sliding charge-density wave (CDW) in NbSe3. For temperatures between 70 K and 120 K and for applied currents up to 40x the threshold current for sliding, the scattering peak for the sliding CDW is significantly broader than that for the pinned CDW, indicating that the sliding state is less correlated than the pinned state. Using scaling analysis, we show that the CDW phase roughness exponent α rises from 0.60 ± 0.10 in the pinned state to 0.80 ± 0.10 in the sliding state.
The prophylactic efficacy of DNA and replication-incompetent adenovirus serotype 5 (Ad5) vaccine ... more The prophylactic efficacy of DNA and replication-incompetent adenovirus serotype 5 (Ad5) vaccine vectors expressing simian immunodeficiency virus (SIV) Gag was examined in rhesus macaques using an SIVmac239 challenge. Cohorts of either Mamu-A*01(�) or Mamu-A*01(�) macaques were immunized with a DNA prime-Ad5 boost regimen; for comparison, a third cohort consisting of Mamu-A*01(�) monkeys was immunized using the Ad5 vector alone for both prime and boost. All animals, along with unvaccinated control cohorts of Mamu-A*01(�) and Mamu-A*01(�) macaques, were challenged intrarectally with SIVmac239. Viral loads were measured in both peripheral and lymphoid compartments. Only the DNA prime-Ad5-boosted Mamu-A*01(�) cohort exhibited a notable reduction in peak plasma viral load (sevenfold) as well as in early set-point viral burdens in both plasma and lymphoid tissues (10-fold) relative to those observed in the control monkeys sharing the same Mamu-A*01 allele. The degree of control in each a...
Dynamic scaling during CDW relaxation from the sliding state
Journal de physique, Dec 1, 1999
ABSTRACT Using time-resolved high-resolution x-ray scattering techniques, we have measured the ev... more ABSTRACT Using time-resolved high-resolution x-ray scattering techniques, we have measured the evolution of the structure of the Q1 charge-density wave in NbSe3 as it relaxes after an applied electric field is turned off. Measurements were made at temperatures between 70 and 120 K and at applied field strengths up to 40x the threshold for sliding. These time-dependent structural data are accurately described by dynamic scaling theory. For threshold field strengths less than the threshold to sliding, the value of the dynamic scaling exponent µ is consistent with the value predicted by assuming that the CDW is an elastic medium. However, for field strengths greater than threshold, µ is significantly smaller, indicating that phase-slip (amplitude fluctuations) is (are) necessary for a correct physical description.
Pigment Analysis of a Landscape by Gustave Courbet
University of Pennsylvania Press, Inc. eBooks, Feb 14, 2023
arXiv: Materials Science, 2019
A major motivation for the scientific study of artworks is to understand their states of preserva... more A major motivation for the scientific study of artworks is to understand their states of preservation and ongoing degradation mechanisms. This enables preservation strategies to be developed for irreplaceable works. Intensely-hued cadmium sulphide (CdS) yellow pigments are of particular interest because these are key to the palettes of many important late 19th and early 20th century masters, including Vincent Van Gogh, Pablo Picasso, Henri Matisse, and Edvard Munch. As these paintings age, their cadmium yellow paints are undergoing severe fading, flaking, and discolouration. These effects are associated with photodegradation, the light-facilitated reactions of CdS with oxygen, moisture, and even the paint binding medium. The use of common optical and X-ray methods to characterize the physical state of the pigment is challenging due to the mixing of the various components of the paint at length scales smaller than their resolution. Here, we present an atomic-scale structural and chem...
Evaluation of HCMV vaccines in rhesus macaques by a novel micro-neutralization assay (113.4)
Journal of Immunology, May 1, 2012
Human cytogemalovirus (HCMV) causes wide-spread infection in adult human populations. Although no... more Human cytogemalovirus (HCMV) causes wide-spread infection in adult human populations. Although no symptoms observed in healthy persons, HCMV infection can cause severe and even life-threatening diseases in immune-compromised individuals. There are lines of evidence that humoral immunity can provide protection against HCMV infection. We have tested several versions of HCMV vaccines based on laboratory strain AD169 with its epithelial tropism restored in rhesus macaques. Vaccines were administered intramuscularly three times. In comparison, recombinant HCMV gB protein vaccine, which showed marginal protections in previous clinical trial, was given with adjuvant MF59. To facilitate the evaluation of these vaccines, we have developed a novel micro-neutralization assay based on the detection of a dominant HCMV antigen expressed in ARPE19 cells, using near infrared dye-labeled immune reagents, to measure HCMV neutralizing activities in serum samples of vaccinated monkeys. Our results showed that AD169 revertant vaccines induced much stronger neutralizing activities than recombinant gB vaccine in rhesus monkeys. The addition of ISCOMATRIX adjuvant (CSL, Ltd) in the vaccine formulation further enhanced its immunogenicity. There were significant boost effects after the second injection, while the third injection did not increase the neutralizing titers above those obtained post the second vaccination.
Journal of Immunological Methods, Feb 1, 2013
This paper describes an approach to surface plasmon resonance (SPR) based epitope mapping, also r... more This paper describes an approach to surface plasmon resonance (SPR) based epitope mapping, also referred to as pairwise antibody footprinting, involving the direct immobilization of an antigen-specific primary mAb to the surface of an SPR interface. This technique offers a more straightforward approach than indirect capture (e.g., via rabbit anti-mouse Fc) as it does not require additional steps to block the unoccupied immobilized anti-Fc to prevent non-specific antibody binding. This is also an alternative to the direct immobilization of an antigen of interest, which may cause conformational changes in the antigen or epitope degradation upon chemical immobilization, particularly in successive regeneration cycles. It is particularly suitable for highly multivalent targets such as virus-like particles (VLPs). Using this technique, we assessed a panel of eight monoclonal antibodies against HPV (human papilloma virus) L1 protein VLPs expressed by Saccharomyces cerevisiae. In the antibody epitope screening studies, HPV16 L1-directed conformational mAbs were clearly distinguished from the linear mAbs and consistent with known epitope information. Additional studies using a linear mAb and a conformational mAb demonstrate the practical application of this technique for characterizing the result of process changes and the consistency of recombinant HPV16 VLPs. The method is readily extensible to other VLPs and VLP-based vaccines.
Clinical and Vaccine Immunology, Aug 1, 2009
In an effort to characterize important epitopes of Staphylococcus aureus iron-regulated surface d... more In an effort to characterize important epitopes of Staphylococcus aureus iron-regulated surface determinant B (IsdB), murine IsdB-specific monoclonal antibodies (MAbs) were isolated and characterized. A panel of 12 MAbs was isolated. All 12 MAbs recognized IsdB in enzyme-linked immunosorbent assays and Western blots; 10 recognized native IsdB expressed by S. aureus. The antigen epitope binding of eight of the MAbs was examined further. Three methods were used to assess binding diversity: MAb binding to IsdB muteins, pairwise binding to recombinant IsdB, and pairwise binding to IsdB-expressing bacteria. Data from these analyses indicated that MAbs could be grouped based on distinct or nonoverlapping epitope recognition. Also, MAb binding to recombinant IsdB required a significant portion of intact antigen, implying conformational epitope recognition. Four MAbs with nonoverlapping epitopes were evaluated for in vitro opsonophagocytic killing (OPK) activity and efficacy in murine challenge models. These were isotype switched from immunoglobulin G1 (IgG1) to IgG2b to potentially enhance activity; however, this isotype switch did not appear to enhance functional activity. MAb 2H2 exhibited OPK activity (>50% killing in the in vitro OPK assay) and was protective in two lethal challenge models and a sublethal indwelling catheter model. MAb 13C7 did not exhibit OPK (<50% killing in the in vitro assay) and was protective in one lethal challenge model. Neither MAb 13G11 nor MAb 1G3 exhibited OPK activity in vitro or was active in a lethal challenge model. The data suggest that several nonoverlapping epitopes are recognized by the IsdB-specific MAbs, but not all of these epitopes induce protective antibodies.
Clinical and Vaccine Immunology, Apr 1, 2014
Human papillomavirus (HPV) is the etiological agent for all cervical cancers, a significant numbe... more Human papillomavirus (HPV) is the etiological agent for all cervical cancers, a significant number of other anogenital cancers, and a growing number of head and neck cancers. Two licensed vaccines offer protection against the most prevalent oncogenic types, 16 and 18, responsible for approximately 70% of cervical cancer cases worldwide and one of these also offers protection against types 6 and 11, responsible for 90% of genital warts. The vaccines are comprised of recombinantly expressed major capsid proteins that self-assemble into virus-like particles (VLPs) and prevent infection by eliciting neutralizing antibodies. Adding the other frequently identified oncogenic types 31, 33, 45, 52, and 58 to a vaccine would increase the coverage against HPV-induced cancers to approximately 90%. We describe the generation and characterization of panels of monoclonal antibodies to these five additional oncogenic HPV types, and the selection of antibody pairs that were high affinity and type specific and recognized conformation-dependent neutralizing epitopes. Such characteristics make these antibodies useful tools for monitoring the production and potency of a prototype vaccine as well as monitoring vaccine-induced immune responses in the clinic.
A fully human monoclonal antibody to Staphylococcus aureus iron regulated surface determinant B (IsdB) with functional activity in vitro and in vivo
Human antibodies, Dec 15, 2010
Nucleation in Submonolayer Electrodeposition
APS, Mar 1, 1998
ABSTRACT We have studied phin situ the ordering of a two-dimensional CuCl crystal electrodeposite... more ABSTRACT We have studied phin situ the ordering of a two-dimensional CuCl crystal electrodeposited on a Pt(111) surface. We simultaneously measured high-resolution time-resolved x-ray scattering and chronoamperometric transients. Both measurements were synchronized with the leading edge of an applied potential step which stimulated the desorption of Cu and subsequent ordering of the CuCl crystal. In all cases, the current transient occurs on a shorter time-scale than the development of crystalline order. The scattered x-ray intensity data (2 × 10^4 data points) vs. time and transverse momentum transfer can be fit to an Avrami-like function with only three parameters. By performing a series of voltage-step experiments, we demonstrate that the ordering time diverges with applied potential phi as tau ~ exp [ 1 / (phi - phi_0) ], consistent with the nucleation and growth of two-dimensional clusters. Monitoring the time-dependent widths of the x-ray peak, we see a narrowing corresponding to the growing clusters. Further information is available at http://www.msc.cornell.edu/ adam
Research paper Design and optimization of a multiplex anti-influenza peptide immunoassay
Scientific Study, Condition Challenges, and Attribution Questions in Yves Tanguy’s Oeuvre
Cultural heritage science, 2022
Proceedings of the National Academy of Sciences of the United States of America, Jan 17, 2013
Human cytomegalovirus (HCMV) can cause serious morbidity/mortality in transplant patients, and co... more Human cytomegalovirus (HCMV) can cause serious morbidity/mortality in transplant patients, and congenital HCMV infection can lead to birth defects. Developing an effective HCMV vaccine is a high medical priority. One of the challenges to the efforts has been our limited understanding of the viral antigens important for protective antibodies. Receptor-mediated viral entry to endothelial/epithelial cells requires a glycoprotein H (gH) complex comprising five viral proteins (gH, gL, UL128, UL130, and UL131). This gH complex is notably missing from HCMV laboratory strains as well as HCMV vaccines previously evaluated in the clinic. To support a unique vaccine concept based on the pentameric gH complex, we established a panel of 45 monoclonal antibodies (mAbs) from a rabbit immunized with an experimental vaccine virus in which the expression of the pentameric gH complex was restored. Over one-half (25 of 45) of the mAbs have neutralizing activity. Interestingly, affinity for an antibody ...
mAbs, 2009
The human D5 monoclonal antibody binds to the highly conserved hydrophobic pocket on the N-termin... more The human D5 monoclonal antibody binds to the highly conserved hydrophobic pocket on the N-terminal heptad repeat (NHR) trimer of HIV-1 gp41 and exhibits modest yet relatively broad neutralization activity. Both binding and neutralization depend on residues in the complementarity determining regions (CDRs) of the D5 IgG variable domains on heavy chain (VH) and light chain (VL). In an effort to increase neutralization activity to a wider range of HIV-1 strains, we have affinity matured the parental D5 scFv by randomizing selected residues in 5 of its 6 CDRs. The resulting scFv variants derived from four different CDR changes showed enhanced binding affinities to gp41 NHR mimetic (5-helix) which correlated to improved neutralization potencies by up to 8-fold. However, when converted to IgG1s, these D5 variants had up to a 12-fold reduction in neutralization potency over their corresponding scFvs despite their slightly enhanced in vitro binding affinities. Remarkably, D5 variant IgG1s bearing residue changes in CDRs that interact with epitope residues N-terminal to the hydrophobic pocket (such as VH CDR3 and VL CDR3) retained more neutralization potency than those containing residue changes in pocketinteracting CDRs (such as VH CDR2). These results provide compelling evidence for the existence of a steric block to an IgG that extends to the gp41 NHR hydrophobic pocket region, and can be a useful guide for developing therapeutic antibodies and vaccines circumventing this block.
Clinical and Vaccine Immunology, 2014
ABSTRACTHuman papillomavirus (HPV) is the etiological agent for all cervical cancers, a significa... more ABSTRACTHuman papillomavirus (HPV) is the etiological agent for all cervical cancers, a significant number of other anogenital cancers, and a growing number of head and neck cancers. Two licensed vaccines offer protection against the most prevalent oncogenic types, 16 and 18, responsible for approximately 70% of cervical cancer cases worldwide and one of these also offers protection against types 6 and 11, responsible for 90% of genital warts. The vaccines are comprised of recombinantly expressed major capsid proteins that self-assemble into virus-like particles (VLPs) and prevent infection by eliciting neutralizing antibodies. Adding the other frequently identified oncogenic types 31, 33, 45, 52, and 58 to a vaccine would increase the coverage against HPV-induced cancers to approximately 90%. We describe the generation and characterization of panels of monoclonal antibodies to these five additional oncogenic HPV types, and the selection of antibody pairs that were high affinity and...
Angewandte Chemie International Edition, 2001
We also acknowledge very helpful discussions with G. E. S. Toombes. details of the SAXS data trea... more We also acknowledge very helpful discussions with G. E. S. Toombes. details of the SAXS data treatment and analysis.)
A fully human monoclonal antibody to Staphylococcus aureus iron regulated surface determinant B (IsdB) with functional activity in vitro and in vivo
Human Antibodies, 2010
A fully human monoclonal antibody (CS-D7, IgG1) specific for the iron regulated surface determina... more A fully human monoclonal antibody (CS-D7, IgG1) specific for the iron regulated surface determinant B (IsdB) of Staphylococcus aureus was isolated from the Cambridge Antibody Technology (CAT) scFv antibody library. As compared to previously described IsdB specific murine monoclonals, CS-D7 has a unique, non-overlapping binding site on IsdB, and exhibits increased in vivo activity. The antibody recognizes a conformational epitope spanning amino acids 50 to 285 and has a binding affinity of 340 (± 75) pM for IsdB. CS-D7 bound to a wide variety of S. aureus strains, but not to an isdB deletion mutant. The antibody mediated opsonophagocytic (OP) killing in vitro and mediated significant protection in vivo. In a murine lethal sepsis model, the antibody conferred protection from death when dosed prior to challenge, but not when dosed after challenge. Importantly, in a central venous catheter (CVC) model in rats, the antibody reduced bacteremia and prevented colonization of indwelling catheters. Protection was observed when rats were dosed with CS-D7 prior to challenge as well as post challenge. IsdB is currently being investigated for clinical efficacy against S. aureus infection, and the activity of this human IsdB specific antibody supplements the growing body of evidence to support targeting this antigen for vaccine development.
towards Less-Conserved Regions and Potential Impact on Vaccine Efficacy in the Step Study
T cell directed HIV vaccines are based upon the induction of CD8+ T cell memory responses that wo... more T cell directed HIV vaccines are based upon the induction of CD8+ T cell memory responses that would be effective in inhibiting infection and subsequent replication of an infecting HIV-1 strain, a process that requires a match or near-match between the epitope induced by vaccination and the infecting viral strain. We compared the frequency and specificity of the CTL epitope responses elicited by the replication-defective Ad5 gag/pol/nef vaccine used in the Step trial with the likelihood of encountering those epitopes among recently sequenced Clade B isolates of HIV-1. Among vaccinees with detectable 15-mer peptide pool ELISpot responses, there was a median of four (one Gag, one Nef and two Pol) CD8 epitopes per vaccinee detected by 9-mer peptide ELISpot assay. Importantly, frequency analysis of the mapped epitopes indicated that there was a significant skewing of the T cell response; variable epitopes were detected more frequently than would be expected from an unbiased sampling of ...
Sliding charge-density waves as rough growth surfaces
ABSTRACT Using high-resolution x-ray scattering techniques we have measured the transverse struct... more ABSTRACT Using high-resolution x-ray scattering techniques we have measured the transverse structure of the sliding charge-density wave (CDW) in NbSe3. For temperatures between 70 K and 120 K and for applied currents up to 40x the threshold current for sliding, the scattering peak for the sliding CDW is significantly broader than that for the pinned CDW, indicating that the sliding state is less correlated than the pinned state. Using scaling analysis, we show that the CDW phase roughness exponent α rises from 0.60 ± 0.10 in the pinned state to 0.80 ± 0.10 in the sliding state.
The prophylactic efficacy of DNA and replication-incompetent adenovirus serotype 5 (Ad5) vaccine ... more The prophylactic efficacy of DNA and replication-incompetent adenovirus serotype 5 (Ad5) vaccine vectors expressing simian immunodeficiency virus (SIV) Gag was examined in rhesus macaques using an SIVmac239 challenge. Cohorts of either Mamu-A*01(�) or Mamu-A*01(�) macaques were immunized with a DNA prime-Ad5 boost regimen; for comparison, a third cohort consisting of Mamu-A*01(�) monkeys was immunized using the Ad5 vector alone for both prime and boost. All animals, along with unvaccinated control cohorts of Mamu-A*01(�) and Mamu-A*01(�) macaques, were challenged intrarectally with SIVmac239. Viral loads were measured in both peripheral and lymphoid compartments. Only the DNA prime-Ad5-boosted Mamu-A*01(�) cohort exhibited a notable reduction in peak plasma viral load (sevenfold) as well as in early set-point viral burdens in both plasma and lymphoid tissues (10-fold) relative to those observed in the control monkeys sharing the same Mamu-A*01 allele. The degree of control in each a...