Hybridomas generated from mice immunized with allotype and H-2-incompatible spleen cells were screened by flow cytometry. Monoclonal antibodies (MAb) to four of the five known specificities of IgD ...were identified. The location of these specificities on the IgD molecule was determined by the ability of a given MAb to bind to cells stripped of the Fab fragment by trypsin proteolysis. Igh-5.1 (present on IgDa and IgDe) and Igh-5.5 (unique to IgDe) were both located on the Fab fragment. Results from cross-blocking experiments suggest that, except for Igh-5.3, MAb which recognize the same specificity bind to the same antigenic determinant. Both the trypsin digest and blocking studies indicate that Igh-5.3 is composed of at least two antigenic determinants. AF6-78.25, a MAb specific for IgM of the b, d, and n haplotypes, was also identified; this MAb defines a new specificity, Igh-6.6. On the basis of the reactivities of these MAb, it appears that although the Igh-Ce and Igh-Cd haplotypes are virtually identical at the Igh-3(gamma 2b), Igh-1(gamma 2a), and Igh-2(alpha) loci, they are highly divergent at the Igh-5(delta) and Igh-6(mu) loci. This indicates that the Igh-Cd haplotype may have resulted from a recombination between Igh-Ce and another haplotype.
Abstract The classification, scoring systems, and response criteria for myelodysplastic syndromes (MDS) have recently been updated and have become widely accepted. In addition, several new effective ...targeted drugs for patients with MDS have been developed. The current article provides a summary of updated and newly proposed markers, criteria, and standards in MDS, with special reference to the diagnostic interface and refinements in evaluations and scoring. Concerning the diagnostic interface, minimal diagnostic criteria for MDS are proposed, and for patients with unexplained cytopenia who do not fulfill these criteria, the term ‘idiopathic cytopenia of uncertain significance’ (ICUS) is suggested. In addition, new diagnostic and prognostic parameters, histopathologic and immunologic determinants, proposed refinements in scoring systems, and new therapeutic approaches are discussed. Respective algorithms and recommendations should facilitate diagnostic and prognostic evaluations in MDS, selection of patients for therapies, and the conduct of clinical trials.
The aim of this study was to establish the therapeutic relevance of the CD33
isoform by developing novel antibodies targeting the IgC domain of CD33. Two novel IgC-targeting antibodies, HL2541 and ...5C11-2, were developed, and CD33 isoforms were assessed using multiple assays in cells overexpressing either CD33
or CD33
isoforms, unmodified acute myeloid leukemia (AML) cell lines and primary AML specimens representing different genotypes for the CD33 splicing single nucleotide polymorphism. CD33
was recognized on cells overexpressing CD33
and unmodified AML cell lines; however, minimal/no cell surface detection of CD33
was observed in primary AML specimens. Both isoforms were detected intracellularly using novel antibodies. Minimal cell surface expression of CD33
on primary AML/progenitor cells warrants further studies on anti-CD33
immunotherapeutics.
•Food system transformation is urgent, requiring rigorous, science-based monitoring to guide public and private decisions and support those who hold decision-makers to account.•Monitoring the whole ...of food systems and the interactions between their components is essential to support the immediate course corrections required to meet global sustainable development goals.•A food systems framework is proposed to define the architecture for a comprehensive monitoring agenda covering five thematic areas and their component indicator domains.•An inclusive process is called for that would select and track indicators for analysis of food systems performance and accountability.
Food systems that support healthy diets in sustainable, resilient, just, and equitable ways can engender progress in eradicating poverty and malnutrition; protecting human rights; and restoring natural resources. Food system activities have contributed to great gains for humanity but have also led to significant challenges, including hunger, poor diet quality, inequity, and threats to nature. While it is recognized that food systems are central to multiple global commitments and goals, including the Sustainable Development Goals, current trajectories are not aligned to meet these objectives. As mounting crises further stress food systems, the consequences of inaction are clear. The goal of food system transformation is to generate a future where all people have access to healthy diets, which are produced in sustainable and resilient ways that restore nature and deliver just, equitable livelihoods.
A rigorous, science-based monitoring framework can support evidence-based policymaking and the work of those who hold key actors accountable in this transformation process. Monitoring can illustrate current performance, facilitate comparisons across geographies and over time, and track progress. We propose a framework centered around five thematic areas related to (1) diets, nutrition, and health; (2) environment and climate; and (3) livelihoods, poverty, and equity; (4) governance; and (5) resilience and sustainability. We hope to call attention to the need to monitor food systems globally to inform decisions and support accountability for better governance of food systems as part of the transformation process. Transformation is possible in the next decade, but rigorous evidence is needed in the countdown to the 2030 SDG global goals.
•PRAME is aberrantly expressed in childhood and adult acute myeloid leukemia and is absent in normal hematopoietic cells.•Mimic TCR CAR T cells effectively target PRAME in vitro and in vivo xenograft ...models.
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Preferentially Expressed Antigen in Melanoma (PRAME), a cancer-testis antigen, provides an ideal target for immunotherapy in acute myeloid leukemia (AML). We have shown expression of PRAME in a significant subset of childhood and adult AML and lack of expression in normal hematopoiesis. Although an intracellular antigen, we developed a novel approach to target PRAME using a chimeric antigen receptor (CAR) construct encoding a targeting domain based on T-cell receptor (TCR) mimic antibodies that target the peptide-HLA complex. We used the antibody sequence from a previously designed TCR mimic (mTCR) antibody, Pr20, that recognizes the PRAME ALY peptide in complex with HLA-A∗02 and verified expression of PRAME in AML cell lines and primary AML blasts. Using the Pr20 antibody sequence, we developed CAR T cells (PRAME mTCRCAR T) to be tested against primary samples from patients with AML and AML cell lines that express the PRAME antigen in the context of HLA-A2 expression. In contrast to appropriate controls, PRAME mTCRCAR T cells demonstrate target-specific and HLA-mediated in vitro activity in OCI-AML2 and THP-1 cell lines, HLA-A2 cell lines expressing the PRAME antigen, and against primary AML patient samples. In vivo cell-derived xenograft models treated with PRAME mTCRCAR T cells demonstrated potent leukemia clearance and improved survival compared with unmodified T-cell controls. Furthermore, the cytolytic activity of PRAME mTCRCAR T cells was enhanced by treating the target cells with interferon gamma, which increases PRAME antigen expression. These results demonstrate the feasibility and efficacy of targeting PRAME with novel PRAME mTCRCAR T cells.
We present a new method to standardize type Ia supernova (SN Ia) luminosities to $\la$0.13 mag using flux ratios from a single flux-calibrated spectrum per SN. Using Nearby Supernova Factory ...spectrophotomery of 58 SNe Ia, we performed an unbiased search for flux ratios that correlate with SN Ia luminosity. After developing the method and selecting the best ratios from a training sample, we verified the results on a separate validation sample and with data from the literature. We identified multiple flux ratios whose correlations with luminosity are stronger than those of light curve shape and color, previously identified spectral feature ratios, or equivalent width measurements. In particular, the flux ratio $\mathcal{R}_{642/443} = F(642~{\rm nm}) / F(443~{\rm nm})$ has a correlation of 0.95 with SN Ia absolute magnitudes. Using this single ratio as a correction factor produces a Hubble diagram with a residual scatter standard deviation of $0.125 \pm 0.011$ mag, compared with $0.161 \pm 0.015$ mag when fit with the SALT2 light curve shape and color parameters x1 and c. The ratio $\mathcal{R}_{642/443}$ is an effective correction factor for both extrinsic dust reddening and instrinsic variations such as those of SN 1991T-like and SN 1999aa-like SNe. When combined with broad-band color measurements, spectral flux ratios can standardize SN Ia magnitudes to ~0.12 mag. These are the first spectral metrics that give robust improvements over the standard normalization methods based upon light curve shape and color, and they provide among the lowest scatter Hubble diagrams ever published.
We present Keck LRIS spectroscopy and g-band photometry of the metal-poor, low-luminosity host galaxy of the super-Chandrasekhar-mass Type Ia supernova SN 2007if. Deep imaging of the host reveals its ...apparent magnitude to be mg = 23.15 ? 0.06, which at the spectroscopically measured redshift of z helio = 0.07450 ? 0.00015 corresponds to an absolute magnitude of Mg = --14.45 ? 0.06. Galaxy g -- r color constrains the mass-to-light ratio, giving a host stellar mass estimate of log(M */M ) = 7.32 ? 0.17. Balmer absorption in the stellar continuum, along with the strength of the 4000 A break, constrains the age of the dominant starburst in the galaxy to be t burst = 123+165 --77 Myr, corresponding to a main-sequence turnoff mass of M/M = 4.6+2.6 --1.4. Using the R 23 method of calculating metallicity from the fluxes of strong emission lines, we determine the host oxygen abundance to be 12 + log(O/H)KK04 = 8.01 ? 0.09, significantly lower than any previously reported spectroscopically measured Type Ia supernova host galaxy metallicity. Our data show that SN 2007if is very likely to have originated from a young, metal-poor progenitor.
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