gebhart/patrepeval huggingface dataset:
Protective monoclonal antibody defines a circumsporozoite-like glycoprotein exoantigen of Cryptosporidium parvum sporozoites and merozoites (1997)

The apicomplexan protozoan parasite Cryptosporidium parvum causes a diarrheal disease in humans and other mammals for which specific therapy and immunoprophylaxis are unavailable. Passive immunization with Abs against whole C. parvum organisms has variable efficacy in immunocompromised or neonatal hosts. Because apical and surface-exposed zoite Ags of the Apicomplexa are critical to infectivity and targets of protective immunity, we examined the ability of mAbs generated against such Ags in C. parvum sporozoites to passively protect against infection and identify biologically relevant parasite molecules. A panel of mAbs was produced against affinity-purified native Ags using sporozoite apical- and surface-reactive mAb C4A1 as binding ligand. One resulting mAb, designated 3E2, elicited prominent morphologic changes in sporozoites and merozoites characterized by rapid and progressive formation, posterior movement, and release of membranous Ag-mAb precipitates. These changes had a striking resemblance to the malarial circumsporozoite precipitate (CSP) reaction. Sporozoite infectivity was completely neutralized after in vitro exposure to 3E2 and the CSP-like reaction. Furthermore, orally administered 3E2 completely prevented or markedly reduced infection in neonatal BALB/c mice. 3E2 bound to apical complex and surface molecules of zoites and was demonstrated in membranous precipitates by immunoelectron microscopy. In Western blots, 3E2 recognized multiple 46 to approximately 770 kDa sporozoite Ags and an approximately 1300-kDa Ag designated CSL, also expressed by merozoites. CSL was characterized as a soluble glycoprotein exoantigen released by infectious sporozoites. Further, CSL was determined to be the molecular species mechanistically involved in the CSP-like reaction by its identification in SDS-PAGE gels and Western blots of purified membranous precipitates. These findings indicate that CSL has a functional role in sporozoite infectivity and is a candidate molecular target for passive or active immunization against cryptosporidiosis.
Symmetric and Unsymmetric Nickel(II) Schiff Base Complexes; Metal-Localized Versus Ligand-Localized Oxidation (1988)

The oxidation of symmetric and unsymmetric nickel(II) Schiff base complexes was examined in acetonitrile by cyclic voltammetry. Unlike nickel(II) bis(salicylaldimine) complexes which undergo oxidative polymerization at the electrode surface, the complexes examined in this study contain at least one β-ketoimine chelate and are irreversibly oxidized at the electrode surface. The mixed chelate complexes are oxidized at potentials midway between those of the symmetric bis(salicylaldimine) and bis(β-ketoimine) complexes, suggesting a metal-localized rather than a ligand-localized oxidation. Oxidation of nickel(II) to nickel(III) followed by rapid intramolecular electron transfer to give reactive ligand-radical species is proposed to explain the irreversible oxidation of the nickel(II) Schiff base complexes.
Potential prognostic, diagnostic and therapeutic markers for human gastric cancer (2014)

The high incidence of gastric cancer (GC) and its consequent mortality rate severely threaten human health. GC is frequently not diagnosed until a relatively advanced stage. Surgery is the only potentially curative treatment. Thus, early screening and diagnosis are critical for improving prognoses in patients with GC. Gastroscopy with biopsy is an appropriate method capable of aiding the diagnosis of specific early GC tumor types; however, the stress caused by this method together with it being excessively expensive makes it difficult to use it as a routine method for screening for GC on a population basis. The currently used tumor marker assays for detecting GC are simple and rapid, but their use is limited by their low sensitivity and specificity. In recent years, several markers have been identiﬁed and tested for their clinical relevance in the management of GC. Here, we review the serum-based tumor markers for GC and their clinical significance, focusing on discoveries from microarray/proteomics research. We also review tissue-based GC tumor markers and their clinical application, focusing on discoveries from immunohistochemical research. This review provides a brief description of various tumor markers for the purposes of diagnosis, prognosis and therapeutics, and we include markers already in clinical practice and various forthcoming biomarkers.
Potent Antibacterial Peptides Generated by Pepsin Digestion of Bovine Lactoferrin (1991)

The antibacterial properties of enzymatic hydrolysates of bovine lactoferrin were examined to determine whether active peptides are produced from this protein. Hydrolysates prepared by cleavage of lactoferrin with porcine pepsin, cod pepsin, or acid protease from Penicillium duponti showed strong activity against Escherichia coli O111, whereas hydrolysates produced by trypsin, papain, or other neutral proteases were much less active. Low molecular weight peptides generated by porcine pepsin cleavage of lactoferrin showed broad-spectrum antibacterial activity, inhibiting the growth of a number of Gram-negative and Gram-positive species, including strains that were resistant to native lactoferrin. The antibacterial potency of the hydrolysate was at least eightfold greater than that of undigested lactoferrin with all strains tested. The active peptides retained their activity in the presence of added iron, unlike native lactoferrin. The effect of the hydrolysate was bactericidal as indicated by a rapid loss of viability of E. coli O111. The lactoferrin hydrolysate described in the present study has commercial value as a natural preservative agent for use in foods and cosmetics, and as a functional component of new clinical foods for prevention or treatment of gastrointestinal disease.
Predisposition to efficient mammary tumor metastatic progression is linked to the breast cancer metastasis suppressor gene Brms1. (2001)

Tumor metastasis is one of the most important clinical aspects of neoplastic disease because patient mortality is frequently attributable to disseminated rather than primary tumors. However, it still is not possible to definitively distinguish those individuals at high risk for disseminated disease, who would benefit from aggressive adjuvant therapy, from the low-risk patients who might be spared the side effects of additional anticancer therapy. To identify factors that predispose toward metastatic disease, we have used a genetic approach. Using a highly metastatic model of mammary cancer, we identified previously inbred mouse strains (DBA/2J, NZB/B1NJ, and I/LnJ) that harbor genetic factors that significantly suppress metastatic efficiency. In this study, we report the results of four experiments to localize the genetic map locations of the metastasis efficiency modifier genes. One statistically significant locus was identified on proximal Chr 19 designated Mtes1. Secondary candidate intervals were detected on Chrs 6, 9, 13, and 17. Interestingly, Mtes1 colocalizes with the murine orthologue of the human breast cancer metastasis suppressor gene Brms1, suggesting that allelic variants of Brms1 might be responsible for the metastasis suppression observed.
Basic fibroblast growth factor and nerve growth factor administered in gel foam rescue medial septal neurons after fimbria fornix transection (1989)

Basic fibroblast growth factor (bFGF) recently has been established as a survival- and transmitter-promoting neurotrophic agent for embryonic neurons in vitro. Its local application to lesioned adult optic and sciatic nerves has been shown to rescue axotomized retinal and sensory neurons that otherwise die. Following transection of the fimbria fornix pathway connecting the medial septum (MS) to the hippocampus, MS neurons undergo severe cell death, which can be prevented partially by infusion of nerve growth factor (NGF). In the same lesion paradigm, we find that 87% of these neurons visualized by cresyl-violet staining have disappeared by 4 weeks after unilateral fimbria fornix transection in adult rats. Implantation of gel foam soaked with 8 micrograms bFGF reduced neuron death to 68%. A similar rescue effect was seen with 0.3 microgram NGF. NGF administered at 20 micrograms reduced cell losses to 54%. Thus, bFGF rescued 22% and NGF at 20 micrograms 38% of the neurons that otherwise would have died. Choline acetyltransferase immunocytochemistry revealed dramatic losses of cholinergic neurons on the lesioned, compared with the unlesioned, side. Cholinergic neuron death was clearly reduced by the bFGF and NGF treatments. Basic FGF, in contrast to NGF, did not prevent a reduction in size of surviving neuronal cell bodies. Considered in the context of FGF being present in brain and hippocampal neurons, our results suggest a possible role for FGF as a neurotrophic factor for CNS neurons in vivo.
HDACs and HDAC inhibitors in colon cancer (2008)

The histone deacetylase (HDAC) family of transcriptional co-repressors have emerged as important regulators of colon cell maturation and transformation. Pharmacological inhibitors of class I and II HDAC activity (HDACi) are potent inducers of growth arrest, differentiation and apoptosis of colon cancer cells in vitro and in vivo, implicating a role for these HDACs in tumor promotion. Consistent with this role, expression of several HDACs are upregulated in colon tumors, while downregulation of specific HDACs inhibits growth of colon cancer cells in vitro and intestinal tumorigenesis in vivo. This review focuses on the function and transcriptional mechanisms by which class I and II HDACs regulate colon cell maturation and transformation, and on the mechanisms by which HDACi induce growth arrest, differentiation and apoptosis of colon cancer cells. The emerging role of the class III HDAC, Sirt1, in colon cancer progression is also discussed.
Complement-derived leukotactic factors in inflammatory synovial fluids of humans (1971)

A large per cent of rheumatoid synovial fluids contain chemotactic activity for rabbit granulocytes (neutrophilic). The chemotactic activity is, in large part, related to the fifth (C5) and sixth (C6) components of human complement; a combination of physical-chemical techniques indicates the activity to be attributable to C567 and C5a, a cleavage product of C5. Many rheumatoid synovial fluids contain a C5-cleaving enzyme which, on the basis of substrate specificity and susceptibility to inhibitors, is very similar to an enzyme extractable from lysosomal granules of human and rabbit granulocytes. Inflammatory nonrheumatoid synovial fluids contain chemotactic activity that is related to cleavage products (C3a) of the third component of human complement (C3). Also found in these fluids is a C3-cleaving enzyme capable of producing C3a. Of the other synovial fluids examined, lupus fluids were remarkable by their total lack of chemotactic activity. These findings record for the first time the presence of complement-derived chemotactic factors in pathological human fluids.
Nano Letters 2020 (2019)

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTNano Letters 2020Teri W. OdomTeri W. OdomMore by Teri W. Odomhttp://orcid.org/0000-0002-8490-292XCite this: Nano Lett. 2020, 20, 1, 1Publication Date (Web):December 18, 2019Publication History Published online18 December 2019Published inissue 8 January 2020https://pubs.acs.org/doi/10.1021/acs.nanolett.9b05084https://doi.org/10.1021/acs.nanolett.9b05084editorialACS PublicationsCopyright © 2019 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views21996Altmetric-Citations3LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (204 KB) Get e-AlertscloseSUBJECTS:Biology,Materials science,Modification,Nanoscience,Nanotechnology Get e-Alerts
A multistage delta-sigma modulator without double integration loop (1986)

A delta-sigma modulator using two interleaved single integration loops to reduce quantization noise by 20dB will be described. The technique avoids the instability of a double integration loop and demonstrates 14b resolution. A 1.5μm CMOS IC operates from a single 5V supply.
Peptide nucleic acid (PNA) — a review (2006)

Abstract Peptide nucleic acid (PNA) is a nucleobase oligomer in which the entire backbone has been replaced by a backbone composed of N ‐(2‐aminoethyl)glycine units. In other words, PNA can be regarded as DNA with a neutral peptide backbone instead of a negatively charged sugar–phosphate backbone. It is chemically stable and resistant to hydrolytic (enzymatic) cleavage and thus not expected to be degraded inside a living cell, although its transportation within the cell is difficult. PNA is capable of recognising specific sequences of DNA and RNA obeying the Watson–Crick hydrogen bonding scheme, and the hybrid complexes exhibit extraordinary thermal stability and unique ionic strength effects. It may also recognise duplex homopurine sequences of DNA to which it binds by strand invasion, forming a stable PNA/DNA/PNA triplex with a looped‐out DNA strand. PNA exhibits superior hybridisation characteristics and improved chemical and enzymatic stability relative to nucleic acids, which is why PNA finds major applications in the diagnostic and pharmaceutical fields. Studies indicate that PNA is capable of inhibiting transcription as well as translation, so it can be used as a new tool for antigene and antisense therapy. Owing to its superior properties, PNA could replace DNA as a probe for many investigation purposes. This paper reviews the synthesis of PNA, its important properties making it a new hot tool in the market and its major applications. Copyright © 2006 Society of Chemical Industry
Current Understanding of the Binding Sites, Capacity, Affinity, and Biological Significance of Metals in Melanin (2007)

Metal chelation is often invoked as one of the main biological functions of melanin. In order to understand the interaction between metals and melanin, extensive studies have been carried out to determine the nature of the metal binding sites, binding capacity, and affinity. These data are central to efforts aimed at elucidating the role metal binding plays in determining the physical, structural, biological, and photochemical properties of melanin. This article examines the current state of understanding of this field.
Illumination and View Position in 3D Visual Recognition (1991)

It is shown that both changes in viewing position and illumination conditions can be compensated for, prior to recognition, using combinations of images taken from different viewing positions and different illumination conditions. It is also shown that, in agreement with psychophysical findings, the computation requires at least a sign bit image as input contours alone are not sufficient.
Staphylokinase-Specific Cell-Mediated Immunity in Humans (2002)

Staphylokinase is a highly fibrin-specific clot-dissolving agent that constitutes a promising drug for clinical development. It is of bacterial origin, and the majority of patients develop neutralizing Ab after its administration. Several antigenic regions, recognized by these Ab, have been identified, but the underlying immunogenic features of staphylokinase remain unknown. In this study, we show that staphylokinase is a T cell-dependent Ag, and that an immunological memory may be acquired, even without administration of staphylokinase. Thrombolysis with staphylokinase provokes the proliferation of staphylokinase-specific T lymphocytes, which remain elevated over 10 mo posttreatment. Interestingly, analysis of a large number of staphylokinase-specific T cell clones isolated from 10 unrelated donors revealed only six distinct immunogenic regions in the molecule. Moreover, five of the six regions are recognized by T lymphocytes from several individuals, indicating that these regions are not restricted to a single HLA-DR allele. Therefore, these new insights can guide the design of variants with a lower immunogenic profile in humans.
Loss of Kv3.1 Tonotopicity and Alterations in cAMP Response Element-Binding Protein Signaling in Central Auditory Neurons of Hearing Impaired Mice (2004)

The promoter for the kv3.1 potassium channel gene is regulated by a Ca2+-cAMP responsive element, which binds the transcription factor cAMP response element-binding protein (CREB). Kv3.1 is expressed in a tonotopic gradient within the medial nucleus of the trapezoid body (MNTB) of the auditory brainstem, where Kv3.1 levels are highest at the medial end, which corresponds to high auditory frequencies. We have compared the levels of Kv3.1, CREB, and the phosphorylated form of CREB (pCREB) in a mouse strain that maintains good hearing throughout life, CBA/J (CBA), with one that suffers early cochlear hair cell loss, C57BL/6 (BL/6). A gradient of Kv3.1 immunoreactivity in the MNTB was detected in both young (6 week) and older (8 month) CBA mice. Although no gradient of CREB was detected, pCREB-immunopositive cells were grouped together in distinct clusters along the tonotopic axis. The same pattern of Kv3.1, CREB, and pCREB localization was also found in young BL/6 mice at a time (6 weeks) when hearing is normal. In contrast, at 8 months, when hearing is impaired, the gradient of Kv3.1 was abolished. Moreover, in the older BL/6 mice there was a decrease in CREB expression along the tonotopic axis, and the pattern of pCREB labeling appeared random, with no discrete clusters of pCREB-positive cells along the tonotopic axis. Our findings are consistent with the hypothesis that ongoing activity in auditory brainstem neurons is necessary for the maintenance of Kv3.1 tonotopicity through the CREB pathway.
Targeting Nanosystems to Human DCs via Fc Receptor as an Effective Strategy to Deliver Antigen for Immunotherapy (2010)

Dendritic cells (DCs) are increasingly being explored as cellular vaccines for tumor immunotherapy, since they provide an effective system of antigen presentation both in vitro and in vivo. An additional advantage of this cell type is that it is possible to target specific antigens through the activation of receptors, such as FcR (the receptor for the IgG Fc fragment) and TLR (toll-like Receptor). Thus, the uptake capacity of DCs can be improved, thereby increasing antigen presentation. This, in turn, would lead to an enhanced immune response, and, in some instances, the tolerance/anergy of immune effector cells present in cancer patients could be reverted. Here we studied various nanotargeting systems, including liposomes and gold nanoparticles of a peptide-based immunotherapeutic vaccine for the treatment of androgen-responsive prostate cancer. Building blocks of the immunogenic peptide consisted of the luteinizing hormone-releasing hormone (LHRH), also known as gonadotropin-releasing hormone (GnRH) peptide (B- and T-cell epitope), in tandem with a T-helper epitope corresponding to the 830-844 region of tetanus toxoid. Three new peptides with several modifications at the N-terminal (palmitoyl, acetyl, and FITC) were synthesized. These peptides also contained a Cys as C-terminal residue to facilitate grafting onto gold nanoparticles. To target different antigen formulations to human DCs, the Fc was activated with a cross-linking spacer to generate a free thiol group and thus facilitate conjugation onto gold nanoparticles, liposomes, and peptide. Our results show that gold nanoparticles and liposomes targeted to FcRs of human DCs are effective antigen delivery carriers and induce a strong immune response with respect to nontargeted LHRH-TT-nanoparticle conjugates and a superior response to that of naked antigens. In addition, dual labeling using gold and FITC-peptide allowed DC tracking by flow cytometry as well as transmission electron microscopy. Nanoparticles were observed to show a homogeneous distribution throughout the cytoplasm. These results open up a new approach to the development of a novel strategy for cancer vaccines.
TMOD-07. NTRK3 GENE FUSIONS DRIVE TUMORIGENESIS IN NOVEL MODELS OF PEDIATRIC HIGH GRADE GLIOMA (2017)

A greater understanding of the unique drivers of pediatric high-grade gliomas (pHGG) is needed as the two-year survival rate is only 10–30%. We recently discovered the presence of structural variants in 47% of pHGG. Recurrent fusions were found involving neurotrophin receptors (NTRK) in 7% of all pHGG and 40% of non-brainstem HGG in infants. One chimeric gene we identified encoded the ETS transcription factor, ETV6, fused to the kinase domain of NTRK3 causing ligand-independent kinase activity. ETV6-NTRK3 has been identified in other neoplasms including congenital-infantile fibrosarcoma and AML. To examine the role of ETV6-NTRK3 in glioma formation in vivo, we developed an implantation model. Cortical astrocytes with conditional loss of p53 in neural stem cells were harvested from mice at P2, transduced with a vector expressing ETV6-NTRK3, and were implanted into the cortex of adult mice. Even with a transduction efficiency of only 1.5–2%, all mice implanted with transduced astrocytes developed HGG with a median survival of 36 days. Next, to study ETV6-NTRK3 in the development of pediatric gliomas, we generated a spontaneous tumor model in which mice expressed a conditional knock-in ETV6-NTRK3 allele and conditional loss of p53 in primitive neural stem cells. Mice expressing ETV6-NTRK3 and null p53 showed rapid development and complete penetrance of high-grade glioma with a median survival of 18 days. Evidence of HGG development was readily detectable by P5, accurately recapitulating onset of pediatric gliomagenesis. Analysis showed ETV6-NTRK3 primary astrocytes had increased proliferation compared to control astrocytes and HGGs driven by ETV6-NTRK3 showed a high proliferative index, MAPK, PI3K and PLCγ activity. In vitro and in vivo models were employed to identify oncogenic targets downstream of NTRK fusions and for preclinical testing of TRK selective inhibitors.
Sequence of a rat immunoglobulin y2c heavy chain constant region cDNA: extensive homology to mouse y3 (1988)

The complete sequence of the rat immunoglobulin gamma 2c heavy chain constant region has been determined by cDNA cloning and by mRNA sequencing. Comparison with other heavy chain genes reveals a high degree of homology (87%) to mouse gamma 3 and suggests that rat and mouse gamma genes separated from a common set of three ancestral genes.
Initial management of trauma (1990)

Trauma is the leading cause of death in young Americans and is responsible for the loss of more productive years of life than heart disease and cancer combined. Initial management of trauma consists of the establishment or maintenance of a patent airway, ensurance of adequate breathing, and resuscitation of the circulation. All of these are accomplished simultaneously with a cursory survey to identify immediately life-threatening injuries and to prevent permanent disability.