gebhart/patrepeval huggingface dataset:
A Retrospective DNA Marker Assessment of the Development of Insect Resistant Soybean (2001)

There has been limited success over the past 30 yr in the development of superior soybean cultivars [ Glycine max (L.) Merr] with insect resistance. Success may be hampered by the quantitative nature of resistance and by linkage drag from resistant plant introduction (PI) donor parents. Soybean insect resistance quantitative trait loci (SIR QTLs) have been identified from PI 229358 and PI 171451 by restriction fragment length polymorphism (RFLP) analysis. The objective of this study was to tag the SIR QTLs from PI 229358 with simple sequence repeat (SSR) markers and to determine the extent to which the SIR QTLs have been introgressed in registered cultivars, germplasm releases, or breeding lines that have resistance derived from this PI or from PI 171451. Marker analysis defined intervals by 5 centimorgans (cM) or less for a SIR QTL on linkage group D1b (SIR‐D1b), and for SIR‐G, SIR‐H, and SIR‐M. SIR QTLs were tracked through pedigrees by evaluating the inheritance of PI alleles at marker loci tightly linked to the QTLs during the phenotypic selection for insect resistance. It was inferred that at least 13 of the 15 SIR genotypes studied had introgressed SIR‐M. PI genome introgression around SIR‐M was measured to assess linkage drag. Some genotypes exhibited a dramatic reduction in the amount of linked PI genome, which likely occurred in response to phenotypic selection for agronomic performance as a means of reducing linkage drag. Only a few genotypes were inferred to possess SIR‐G or SIR‐H, and no genotypes possessed SIR‐D1b. The results of this study indicate that marker‐assisted selection for SIR QTLs is needed to introgress these loci into elite genetic backgrounds.
Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution (2014)

The newly emerging Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes a Severe Acute Respiratory Syndrome-like disease with ∼43% mortality. Given the recent detection of virus in dromedary camels, zoonotic transfer of MERS-CoV to humans is suspected. In addition, little is known about the role of human neutralizing Ab (nAb) pressure as a driving force in MERS-CoV adaptive evolution. Here, we used a well-characterized nonimmune human Ab-phage library and a panning strategy with proteoliposomes and cells to identify seven human nAbs against the receptor-binding domain (RBD) of the MERS-CoV Spike protein. These nAbs bind to three different epitopes in the RBD and human dipeptidyl peptidase 4 (hDPP4) interface with subnanomolar/nanomolar binding affinities and block the binding of MERS-CoV Spike protein with its hDPP4 receptor. Escape mutant assays identified five amino acid residues that are critical for neutralization escape. Despite the close proximity of the three epitopes on the RBD interface, escape from one epitope did not have a major impact on neutralization with Abs directed to a different epitope. Importantly, the majority of escape mutations had negative impacts on hDPP4 receptor binding and viral fitness. To our knowledge, these results provide the first report on human nAbs against MERS-CoV that may contribute to MERS-CoV clearance and evolution. Moreover, in the absence of a licensed vaccine or antiviral for MERS, this panel of nAbs offers the possibility of developing human mAb-based immunotherapy, especially for health-care workers.
Converting a Maltose Receptor into a Nascent Binuclear Copper Oxygenase by Computational Design (2002)

Computational protein design methods were used to identify mutations that are predicted to introduce a binuclear copper center coordinated by six histidines, replacing the maltose-binding site in Escherichia coli maltose-binding protein (MBP) with an oxygen-binding site. A small family of five candidate designs consisting of 9 to 10 mutations each was constructed by oligonucleotide-directed mutagenesis. These mutant proteins were expressed and purified, and their stability, copper- and cobalt-binding properties, and interactions of the resulting metalloprotein complexes with azide, hydrogen peroxide, and dioxygen were characterized. We identified one 10-fold mutant, MBP.Hc.E, that can form Cu(II)(2) and Co(II)(2) complexes that interact with H(2)O(2) and O(2). The Co(II)(2) protein reacts with H(2)O(2) to form a complex that is spectroscopically similar to a synthetic model that structurally mimics the oxy-hemocyanin core, whereas the Cu(II)(2) protein reacted with O(2) or H(2)O(2) does not. We postulate that the equilibrium between the open and closed conformations of MBP allows species with variable Cu-Cu distances to form, and that such species can bind ligands in geometries that are not observed in natural type III centers. Introduction of one additional mutation in the hinge region of MBP, I329F, known to favor formation of the closed state, results in a binuclear copper center that when reacted with low concentrations of H(2)O(2) mimics the spectroscopic signature of oxy-hemocyanin.
Blinatumomab for the Treatment of Philadelphia Chromosome–Negative, Precursor B-cell Acute Lymphoblastic Leukemia (2015)

Blinatumomab is a CD19/CD3 bispescific antibody designed to redirect T cells toward malignant B cells and induce their lysis. It recently gained accelerated approval by the FDA for the treatment of relapsed or refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (RR-ALL). In the phase II trial that served as the basis for approval, blinatumomab demonstrated significant single-agent activity and induced remission [complete remission (CR) and CR with incomplete recovery of peripheral blood counts (CRh)] in 43% of 189 adult patients with RR-ALL; the majority of responders (82%) also attained negative minimal residual disease (MRD(-)) status that did not generally translate into long-term remissions in most cases. Additional studies show that blinatumomab can induce high response rates associated with lasting remissions in patients in first remission treated for MRD positivity, suggesting a role for blinatumomab in the upfront, MRD-positive setting. Blinatumomab infusion follows a predictable immunopharmacologic profile, including early cytokine release that can be associated with a clinical syndrome, T-cell expansion, and B-cell depletion. Neurologic toxicities represent a unique toxicity that shares similarities with adverse effects of other T-cell engaging therapies. Further studies are needed to clarify the optimal disease setting and timing for blinatumomab therapy. Additional insights into the pathogenesis, risk factors, and prevention of neurologic toxicities as well as a better understanding of the clinical consequences and biologic pathways that are associated with drug resistance are needed.
Key Factors for Enhanced Results of Matrix Stimulation Treatments (1988)

ABSTRACT Most of the failures of matrix stimulation treatments can be imputed to incorrect field procedures. To improve the success ratio of the jobs, the tailoring of field stimulation procedures must be strictly linked with the clear identification of the target and with the optimization of the design. Objectives are set to meet different well situations, and require specific design and field procedures. Maximizing the injection pressure andrate during matrix stimulations has proven to be a very successful technique, particularly effective over extensive pay zones.
Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens. (1992)

The lymphocyte activation gene 3 (LAG-3), expressed in human activated T and natural killer (NK) cells, is closely related to CD4 at the gene and protein levels. We report here the initial characterization of the LAG-3-encoded protein. We have generated two monoclonal antibodies after immunization of mice with a 30-amino acid peptide that corresponds to an exposed extra loop region present in the LAG-3 immunoglobulin-like first domain. The reactivity of these reagents is directed against LAG-3 since they recognize both membrane-expressed and soluble recombinant LAG-3 molecules produced in a baculovirus expression system. The two antibodies are likely to react with the same or closely related epitope (termed LAG-3.1) exposed on the LAG-3 first domain extra loop, as assessed in competition experiments on LAG-3-expressing activated lymphocytes. Cellular distribution analysis indicated that the LAG-3.1 epitope is expressed on activated T (both CD4+ and CD8+ subsets) and NK cells, and not on activated B cells or monocytes. In immunoprecipitation experiments performed on activated T and NK cell lysates, a 70-kD protein was detected after SDS-PAGE analysis. 45-kD protein species were also immunoprecipitated. Both the 70- and 45-kD proteins were shown to be N-glycosylated. In Western blot analysis, only the former molecule was recognized by the anti-LAG-3 antibodies, demonstrating that it is LAG-3 encoded. These anti-LAG-3 antibodies were used to investigate whether the LAG-3 protein interacts with the CD4 ligands. By using a high-level expression cellular system based on COS-7 cell transfection with recombinant CDM8 vectors and a quantitative cellular adhesion assay, we demonstrate that rosette formation between LAG-3-transfected COS-7 cells and human leukocyte antigen (HLA) class II-bearing B lymphocytes is specifically dependent on LAG-3/HLA class II interaction. In contrast to CD4, LAG-3 does not bind the human immunodeficiency virus gp120. This initial characterization will guide further studies on the functions of this molecule, which may play an important role in immune responses mediated by T and NK lymphocytes.
The clinical toxicology of gamma-hydroxybutyrate, gamma-butyrolactone and 1,4-butanediol (2012)

GHB poisoning can cause potentially life-threatening CNS and respiratory depression, requiring appropriate, symptom-directed supportive care to ensure complete recovery. Withdrawal from GHB may continue for up to 21 days and can be life-threatening, though treatment with benzodiazepines is usually effective.
Brominated Hydroxyquinoline as a Photolabile Protecting Group with Sensitivity to Multiphoton Excitation (2002)

The synthesis and photochemistry of a new photolabile protecting group for carboxylic acids based on 8-bromo-7-hydroxyquinoline (BHQ) is described. BHQ possesses a greater single photon quantum efficiency than 4,5-dimethoxy-4-nitrobenzyl ester (DMNB) and 6-bromo-7-hydroxycoumarin-4-ylmethyl (Bhc), and it has sufficient sensitivity to multiphoton-induced photolysis for use in vivo. Its increased solubility and low fluorescence make it quite useful as a caging group for biological messengers. [structure: see text]
Selective Usage of VH Genes in Adult Human B Lymphocyte Repertoires (1997)

The authors have compared the VH gene utilization patterns among small resting immunocompetent B cells and large naturally activated B lymphocytes of healthy human adults. They employed a non-radioactive RNA in situ hybridization technique that allows detection of VH gene family expression at the single cell level. Pokeweed mitogen stimulated and unmanipulated mononuclear cells from peripheral blood and spleen of unrelated individuals were hybridized to digoxigenin-labelled antisense RNA probes specific for human VH families 1-6 and for the constant region genes C mu and C gamma. The observed VH gene family utilization patterns did not correlate with the genomic complexity of human VH genes. The VH3 gene family was most frequently used among resting B cells in both peripheral blood and spleen. Among naturally activated lymphocytes the VH6 gene was markedly over-represented, while expression of the VH1 and VH3 gene families was decreased. The data show that V-region mediated selection participates in shaping the peripheral antibody repertoire in healthy adults.
Survival Advantage in Patients with Metastatic Breast Cancer Receiving Endocrine Therapy plus Sialyl Tn-KLH Vaccine: Post Hoc Analysis of a Large Randomized Trial (2013)

Adding STn-KLH to endocrine therapy may improve clinical outcomes with few adverse effects for women with metastatic breast cancer.
Vaccination of Patients with Small-Cell Lung Cancer with Synthetic Fucosyl GM-1 Conjugated to Keyhole Limpet Hemocyanin (2004)

Vaccination with the synthetic fucosyl GM1-KLH conjugate induces an IgM antibody response against fucosyl GM1 and tumor cells expressing fucosyl GM1, comparable with the response induced by the bovine derivative. We plan to combine synthetic fucosyl GM1 vaccine at a dose of 30 microg with vaccines against three other antigens-GM2, Globo H, and polysialic acid-to test in patients with SCLC after initial chemotherapy.
Natural Killer Cells (1986)

Named for their apparent ability to function without prior sensitization, NK cells are the newest additions to the growing cast of immunopathologic effectors, which includes antibodies and immune complexes as well as cytolytic T cells and K cells. The understanding of NK activity has progressed to a level that permits investigators to consider its clinical exploitation in antitumor therapy.
Staphylococcus aureus Manganese Transport Protein C Is a Highly Conserved Cell Surface Protein That Elicits Protective Immunity Against S. aureus and Staphylococcus epidermidis (2012)

Staphylococcus aureus and other staphylococci cause severe human disease, and there are currently no vaccines available. We evaluated whether manganese transport protein C (MntC), which is conserved across the staphylococcal species group, could confer protection against S. aureus and Staphylococcus epidermidis. In vivo analysis of S. aureus MntC expression revealed that expression occurs very early during the infectious cycle. Active immunization with MntC was effective at reducing the bacterial load associated with S. aureus and S. epidermidis infection in an acute murine bacteremia model. Anti-MntC monoclonal antibodies have been identified that can bind S. aureus and S. epidermidis cells and are protective in an infant rat passive protection model and induce neutrophil respiratory burst activity. This is the first description of a protein that has the potential to provide protection across the staphylococcal species group.
Biomimetic Polymer/Apatite Composite Scaffolds for Mineralized Tissue Engineering (2004)

Abstract Summary: The material surface must be considered in the design of scaffolds for bone tissue engineering so that it supports bone cells adhesion, proliferation and differentiation. A biomimetic approach has been developed as a 3D surface modification technique to grow partially carbonated hydroxyapatite (the bonelike mineral) in prefabricated, porous, polymer scaffolds using a simulated body fluid in our lab. For the rational design of scaffolding materials and optimization of the biomimetic process, this work focused on various materials and processing parameters in relation to apatite formation on 3D polymer scaffolds. The apatite nucleation and growth in the internal pores of poly( L ‐lactide) and poly( D , L ‐lactide) scaffolds were significantly faster than in those of poly(lactide‐ co ‐glycolide) scaffolds in simulated body fluids. The apatite distribution was significantly more uniform in the poly( L ‐lactide) scaffolds than in the poly(lactide‐ co ‐glycolide) scaffolds. After incubation in a simulated body fluid for 30 d, the mass of poly( L ‐lactide) scaffolds increased approximately 40%, whereas the mass of the poly(lactide‐ co ‐glycolide) scaffolds increased by about 15% (see Figure). A higher ionic concentration and higher pH value of the simulated body fluid enhanced apatite formation. The effects of surface functional groups on apatite nucleation and growth were found to be more complex in 3D scaffolds than on 2D films. Surprisingly enough, it was found that carboxyl groups significantly reduced the apatite formation, especially on the internal pore surfaces of 3D scaffolds. These findings are critically important in the rational selection of materials and surface design of 3D scaffolds for mineralized tissue engineering and may contribute to the understanding of biomineralization as well. SEM micrograph of a poly( L ‐lactide) scaffold. image SEM micrograph of a poly( L ‐lactide) scaffold.
Phase II Trial of the Anti-GD2Monoclonal Antibody 3F8 and Granulocyte-Macrophage Colony-Stimulating Factor for Neuroblastoma (2001)

3F8/GM-CSF is well tolerated and shows promise for treatment of minimal residual NB in BM.
Recommendations on the Use of 18F-FDG PET in Oncology (2008)

(18)F-FDG PET should be used as an imaging tool additional to conventional radiologic methods such as CT or MRI; any positive finding that could lead to a clinically significant change in patient management should be confirmed by subsequent histopathologic examination because of the risk of false-positive results. (18)F-FDG PET should be used in the appropriate clinical setting for the diagnosis of head and neck, lung, or pancreatic cancer and for unknown primary tumor. PET is also indicated for staging of breast, colon, esophageal, head and neck, and lung cancer and of lymphoma and melanoma. In addition, (18)F-FDG PET should be used to detect recurrence of breast, colorectal, head and neck, or thyroid cancer and of lymphoma.
Yersinia enterocolitica invasin triggers phagocytosis via beta1 integrins, CDC42Hs and WASp in macrophages (2001)

The Yersinia outer surface protein invasin binds to beta1 integrins on target cells and has been shown to trigger phagocytic uptake by macrophages. Here, we investigated the role of the actin regulator Wiskott-Aldrich syndrome protein (WASp), its effector the Arp2/3 complex and the Rho-GTPases CDC42Hs, Rac and Rho in invasin/beta1 integrin-triggered phagocytosis. During uptake of invasin-coated latex beads, the alpha5beta1 integrin, WASp and the Arp2/3 complex were recruited to the developing actin-rich phagocytic cups in primary human macrophages. Blockage of beta1 integrins by specific antibodies, inhibition of Arp2/3 function by microinjection of inhibitors or the use of WASp knockout macrophages inhibited phagocytic cup formation and uptake. Furthermore, microinjection of the dominant negative GTPase mutants N17CDC42Hs, N17Rac or the Rho-specific inhibitor C3-transferase into macrophages greatly attenuated invasin-induced formation of cups. These data suggest that during invasin-triggered phagocytosis beta1 integrins activate actin polymerization via CDC42Hs, its effector WASp and the Arp2/3 complex. The contribution of Rac and Rho to phagocytic cup formation also suggests a complex interplay between different Rho GTPases during phagocytosis of pathogens.
Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA (1992)

Melanocytes and melanoma cells are known to possess receptors for melanocyte stimulating hormone (MSH). A cDNA clone, designated 11D, has been isolated from human melanoma cells and encodes a MSH receptor. The cloned cDNA encodes a 317 amino acid protein with transmembrane topography characteristics of a G-protein-coupled receptor, but it does not show striking similarity to already published sequences of other G-protein-coupled receptors. When 11D cDNA is expressed in COS-7 cells, it binds an 125I-labelled MSH analogue (NDP-MSH) in a specific manner. The bound ligand could be displaced by melanotropic peptides, alpha-MSH, beta-MSH, gamma-MSH and ACTH (adrenocorticotropic hormone), but not by the non-melanotropic peptide, beta-endorphin. This is the first report of the cloning of the receptor gene of the melanotropin receptor family.
The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI): a review of their usefulness and validity in rheumatoid arthritis. (2006)

Composite indices or pooled indices are useful tools for the evaluation of disease activity in patients with rheumatoid arthritis (RA). They allow the integration of various aspects of the disease into a single numerical value, and may therefore facilitate consistent patient care and improve patient compliance, which both can lead to improved outcomes. The Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) are two new tools for the evaluation of disease activity in RA. They have been developed to provide physicians and patients with simple and more comprehensible instruments. Moreover, the CDAI is the only composite index that does not incorporate an acute phase response and can therefore be used to conduct a disease activity evaluation essentially anytime and anywhere. These two new tools have not been developed to replace currently available instruments such as the DAS28, but rather to provide options for different environments. The comparative construct, content, and discriminant validity of all three indices--the DAS28, the SDAI, and the CDAI--allow physicians to base their choice of instrument on their infrastructure and their needs, and all of them can also be used in clinical trials.
Target-Enrichment Through Amplification of Hairpin-Ligated Universal Targets for Next-Generation Sequencing Analysis (2011)

With rapid development of next-generation sequencing (NGS) technologies, it is becoming increasingly feasible to sequence entire genomes of various organisms from virus to human. However, in many occasions, it is still more practical to sequence and analyze only small regions of the entire genome that are informative for the purpose of the experiment. Although many target-enrichment or target capture methods exist, each method has its own strength and weakness in terms of the number of enriched targets, specificity, drop-off rate, and uniformity in capturing target DNA sequences. Many applications require a consistently low drop-off rate and high uniformity of enriched targets for routine collection of meaningful data. Here, we describe a simple and robust PCR-based protocol that can allow simultaneous amplification of numerous target regions. This method employs target-specific hairpin selectors to create DNA templates that contain target regions flanked by common universal priming sequences. We demonstrated the utility of this method by applying it for simultaneous amplification of 21 targets in the range of 191-604 bp from 41 different Salmonella strains using bar-coded universal primers. Analysis of 454 FLX pyrosequencing data demonstrated the promising performance of this method in terms of specificity and uniformity. This method, with great potential for robust amplification of hundreds of targets, should find broad applications for efficient analysis of multiple genomic targets for various experimental goals.