gebhart/patrepeval huggingface dataset:
Cytochemical Demonstration of Oxidative Damage in Alzheimer Disease by Immunochemical Enhancement of the Carbonyl Reaction with 2,4-Dinitrophenylhydrazine (1998)

Formation of carbonyls derived from lipids, proteins, carbohydrates, and nucleic acids is common during oxidative stress. For example, metal-catalyzed, "site-specific" oxidation of several amino acid side-chains produces aldehydes or ketones, and peroxidation of lipids generates reactive aldehydes such as malondialdehyde and hydroxynonenal. Here, using in situ 2,4-dinitrophenylhydrazine labeling linked to an antibody system, we describe a highly sensitive and specific cytochemical technique to specifically localize biomacromolecule-bound carbonyl reactivity. When this technique was applied to tissues from cases of Alzheimer disease, in which oxidative events including lipoperoxidative, glycoxidative, and other oxidative protein modifications have been reported, we detected free carbonyls not only in the disease-related intraneuronal lesions but also in other neurons. In marked contrast, free carbonyls were not found in neurons or glia in age-matched control cases. Importantly, this assay was highly specific for detecting disease-related oxidative damage because the site of oxidative damage can be assessed in the midst of concurrent age-related increases in free carbonyls in vascular basement membrane that would contaminate biochemical samples subjected to bulk analysis. These findings demonstrate that oxidative imbalance and stress are key elements in the pathogenesis of Alzheimer disease.
A client side measurement scheme for request routing in virtual open content delivery networks (2003)

A content delivery network (CDN) routes a client's request to an edge server that can best serve the content at the time. Effective request routing is heavily dependent on up-to-date information of server loads and the network condition. We propose a novel client side measurement scheme that measures both server load, and the network condition, in a single measurement. The scheme is distributed, does not require any modification to the clients, and is compatible with existing client and server software. By experimenting on the existing Internet, we demonstrate that this measurement metric is highly correlated with total page loading time. Combined with request-routing, our measurement method provides an efficient client request redirection system that is totally transparent to the content provider, and facilitates the deployment of virtual open CDNs.
Development of a ‘collect and punch’ cold vapour inductively coupled plasma mass spectrometric method for the direct determination of mercury at nanograms per litre levels (1998)

A highly sensitive ‘collect and punch’ CV–ICP-MS method for the direct determination of mercury at ng l–1 levels is described. Mercury, after reduction to elemental form with SnCl2, was collected in a glass chamber prior to injection into the plasma and the time resolved acquisition mode was used for signal measurement. This arrangement provided a 10–15-fold enhancement of sensitivity compared with continuous vapour injection. The detection limit (3s) of the method was close to 6 ng l–1. Linear calibration was obtained over three orders of magnitude of concentration. The method was validated through the analysis of NIST SRM 1566a Oyster Tissue. Mercury at the 50 ng l–1 level in aqueous solutions can be determined with a precision of approximately 2%. This method is much simpler than the amalgamation approaches for the determination of mercury at these levels.
B.1.617.2 enters and fuses lung cells with increased efficiency and evades antibodies induced by infection and vaccination (2021)

The Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), B.1.617.2, emerged in India and has spread to over 80 countries. B.1.617.2 replaced B.1.1.7 as the dominant virus in the United Kingdom, resulting in a steep increase in new infections, and a similar development is expected for other countries. Effective countermeasures require information on susceptibility of B.1.617.2 to control by antibodies elicited by vaccines and used for coronavirus disease 2019 (COVID-19) therapy. We show, using pseudotyping, that B.1.617.2 evades control by antibodies induced upon infection and BNT162b2 vaccination, although to a lesser extent as compared to B.1.351. We find that B.1.617.2 is resistant against bamlanivimab, a monoclonal antibody with emergency use authorization for COVID-19 therapy. Finally, we show increased Calu-3 lung cell entry and enhanced cell-to-cell fusion of B.1.617.2, which may contribute to augmented transmissibility and pathogenicity of this variant. These results identify B.1.617.2 as an immune evasion variant with increased capacity to enter and fuse lung cells.
Dynamics of Particle Growth and Electrochemical Surface Area Loss due to Platinum Dissolution (2014)

A model for coalescence/sintering of Pt nanoparticles is developed to analyze particle growth and electrochemical surface area (ECSA) loss measured in aqueous tests and in catalyst-coated membrane and gas diffusion electrode-containing single fuel cells. The model combines a non-ideal solid solution theory for Pt dissolution with the dynamics of particle size evolution considering particle growth by Ostwald ripening and coalescence/sintering. Results from the model indicate that the observed growth in particle size and loss in ECSA in accelerated tests are primarily due to coalescence/sintering resulting from Pt dissolution and redeposition between particles. An enthalpy of dissolution of 49.3 kJ.mol−1 and an effective heat of fusion of 28.2 kJ.mol−1 for particle coalescence/sintering have been empirically determined from the measured temperature dependence of particle growth. The model suggests that higher Pt solubility in the presence of oxygen is responsible for enhanced particle growth and ECSA loss in accelerated tests in H2/air as compared to H2/N2. The model also indicates that the dissolution rate constant must be reduced by two orders of magnitude to explain the measured decrease in ECSA loss of the Pt cathode catalyst after 10,000 square potential cycles at 80°C when the relative humidity is decreased from 100% to 30%.
Langmuir−Blodgett Nanorod Assembly (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTLangmuir−Blodgett Nanorod AssemblyFranklin Kim, Serena Kwan, Jennifer Akana, and Peidong YangView Author Information Department of Chemistry, University of California Berkeley, California 94720 Cite this: J. Am. Chem. Soc. 2001, 123, 18, 4360–4361Publication Date (Web):April 11, 2001Publication History Received21 December 2000Published online11 April 2001Published inissue 1 May 2001https://pubs.acs.org/doi/10.1021/ja0059138https://doi.org/10.1021/ja0059138rapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views7256Altmetric-Citations535LEARN 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 Other access optionsGet e-Alertsclose SUBJECTS:Monolayers,Nanorods,Phase transitions,Thin films,Transmission electron microscopy Get e-Alerts
Disorders in cell circuitry during multistage carcinogenesis: the role of homeostasis (2000)

The multistage process of carcinogenesis involves the progressive acquisition of mutations, and epigenetic abnormalities in the expression, of multiple genes that have highly diverse functions. An important group of these genes are involved in cell cycle control. Thus, cyclin D1 is frequently overexpressed in a varety of human cancers. Cylin D1 plays a critical role in carcinogenesis because (i) overexpression enhances cell transformation and tumorigenesis, and enhances the amplification of other genes, and (ii) an antisense cyclin D1 cDNA reverts the malignant phenotype of carcinoma cells. Therefore, cyclin D1 may be a useful biomarker in molecular epidemiology studies, and inhibitors of its function may be useful in both cancer chemoprevention and therapy. We discovered a paradoxical increase in the cell cycle inhibitors protein p27(Kip1) in a subset of human cancers, and obtained evidence for homeostatic feedback loops between cyclins D1 or E and p27(Kip1). Furthermore, derivatives of HT29 colon cancer cells with increased levels of p27(Kip1) showed increased sensitivity to induction of differentiation. This may explain why decreased p27(Kip1) in a subset of human cancers is associated with a high grade (poorly differentiated) histology and poor prognosis. Agents that increase cellular levels of p27(Kip1) may, therefore, also be useful in cancer therapy. Using an antisense Rb oligonucleotide we obtained evidence that the paradoxical increase in pRb often seen in human colon cancers protects these cells from growth inhibition and apopotosis. On the basis of these, and other findings, we hypothesize that homeostatic feedback mechanisms play a critical role in multistage carcinogenesis. Furthermore, because of their bizarre circuitry, cancer cells suffer from 'gene addiction' and 'gene hypersensitivity' disorders that might be exploited in both cancer prevention and chemotherapy.
MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program (2013)

Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). We show that MYC/BCL2 protein coexpression occurred significantly more commonly in the ABC subtype. Patients with the ABC or GCB subtype of DLBCL had similar prognoses with MYC/BCL2 coexpression and without MYC/BCL2 coexpression. Consistent with the notion that the prognostic difference between the 2 subtypes is attributable to MYC/BCL2 coexpression, there is no difference in gene expression signatures between the 2 subtypes in the absence of MYC/BCL2 coexpression. DLBCL with MYC/BCL2 coexpression demonstrated a signature of marked downregulation of genes encoding extracellular matrix proteins, those involving matrix deposition/remodeling and cell adhesion, and upregulation of proliferation-associated genes. We conclude that MYC/BCL2 coexpression in DLBCL is associated with an aggressive clinical course, is more common in the ABC subtype, and contributes to the overall inferior prognosis of patients with ABC-DLBCL. In conclusion, the data suggest that MYC/BCL2 coexpression, rather than cell-of-origin classification, is a better predictor of prognosis in patients with DLBCL treated with R-CHOP.
Spatially Addressable Multiprotein Nanoarrays Templated by Aptamer-Tagged DNA Nanoarchitectures (2007)

Here we generalize a highly programmable strategy to self-assemble multiprotein nanoarrays with deterministic positional addressability. These protein nanoarrays were templated by aptamer-tagged DNA nanoarchitectures. Arrays of proteins with precisely controlled positions and interprotein spacings offer great potential in proteomics, tissue engineering, and medical diagnostics.
Autonomous and nonautonomous Notch functions for embryonic muscle and epidermis development in Drosophila (1996)

The Notch (N) gene encodes a cell signaling protein that mediates neuronal and epidermal determination in Drosophila embryos. N also regulates several aspects of myogenic development; embryos lacking N function have too many muscle founder cells and fail to properly differentiate somatic muscle. To identify cell-autonomous requirements for Notch function during muscle development, we expressed a Notch minigene in the mesoderm, but not in the ectoderm, of amorphic N-embryos. In these embryos, muscle founder hypertrophy is rescued, indicating that Notch is autonomously required by mesoderm cells to regulate the proper number of muscle founders. However, somatic muscle differentiation is only partially normalized, suggesting that Notch is also required in the ectoderm for proper muscle development. Additionally, mesodermal expression of Notch partially rescues epidermal development in overlying neurogenic ectoderm. This is unexpected, since previous studies suggest that Notch is autonomously required by proneural ectoderm cells for epidermal development. Mesodermal expression of a truncated Notch protein lacking the extracellular domain does not rescue ventral epidermis, suggesting that the extra-cellular domain of Notch can non-autonomously rescue epidermal development across germ layers.
[Long-term evolution of membranoproliferative glomerulonephritis in adults : spontaneous clinical remission in 13 cases with proven regression of glomerular lesions in 5 cases (author's transl)]. (1982)

188 patients with type I MPGN were followed from 1957 to 1975. At last examination, 53% of patients with pure MPGN and 66% of those with lobular MPGN had renal insufficiency; 28 other patients showed clinical improvement and 13 of these had permanent complete remission. In all of these 13 cases, (10 pure MPGN and 3 lobular forms), the clinical remission was spontaneous and occurred 2 to 16 years after the apparent onset. At the time of the first renal biopsy, 7 of these patients had a nephrotic syndrome, 2 had hypertension and 1 had renal failure. A second biopsy was obtained in 5 patients during the clinical remission period and showed in all cases a clear regression of the glomerular lesions. The possibility of spontaneous permanent clinical remission in MPGN should be considered in the indications and methods of treatment and the interpretation of their results.
A Small Molecule Antagonist of PD-1/PD-L1 Interactions Acts as an Immune Checkpoint Inhibitor for NSCLC and Melanoma Immunotherapy (2021)

Immune checkpoint inhibitors, such as monoclonal antibodies targeting programmed death 1 (PD-1) and programmed death ligand-1 (PD-L1), have achieved enormous success in the treatment of several cancers. However, monoclonal antibodies are expensive to produce, have poor tumor penetration, and may induce autoimmune side effects, all of which limit their application. Here, we demonstrate that PDI-1 (also name PD1/PD-L1 inhibitor 1), a small molecule antagonist of PD-1/PD-L1 interactions, shows potent anti-tumor activity <i>in vitro</i> and <i>in vivo</i> and acts by relieving PD-1/PD-L1-induced T cell exhaustion. We show that PDI-1 binds with high affinity to purified human and mouse PD-1 and PD-L1 proteins and is a competitive inhibitor of human PD-1/PD-L1 binding <i>in vitro</i>. Incubation of <i>ex vivo</i> activated human T cells with PDI-1 enhanced their cytotoxicity towards human lung cancer and melanoma cells, and concomitantly increased the production of granzyme B, perforin, and inflammatory cytokines. Luciferase reporter assays showed that PDI-1 directly increases TCR-mediated activation of NFAT in a PD-1/PD-L1-dependent manner. In two syngeneic mouse tumor models, the intraperitoneal administration of PDI-1 reduced the growth of tumors derived from human PD-L1-transfected mouse lung cancer and melanoma cells; increased and decreased the abundance of tumor-infiltrating CD8+ and FoxP3+ CD4+ T cells, respectively; decreased the abundance of PD-L1-expressing tumor cells, and increased the production of inflammatory cytokines. The anti-tumor effect of PDI-1 <i>in vivo</i> was comparable to that of the anti-PD-L1 antibody atezolizumab. These results suggest that the small molecule inhibitors of PD-1/PD-L1 may be effective as an alternative or complementary immune checkpoint inhibitor to monoclonal antibodies.
Protease phenotype of constitutive connective tissue and of induced mucosal mast cells in mice is regulated by the tissue (2011)

Mouse mast cells (MCs) express a large number of serine proteases including tryptases, mouse mast cell protease (mMCP)-6 and -7; chymases, mMCP-1, -2, and -4; and an elastase, mMCP-5; along with carboxypeptidase-A3 (CPA3). In helminth-infected mouse intestine, distinct protease phenotypes are observed for connective tissue MCs (CTMCs) (mMCP-4(+)-7(+), and CPA3(+)) and mucosal MCs (MMCs) (mMCP-1(+) and 2(+)). To determine whether the protease phenotype was regulated by the tissue, we compared the phenotype of constitutive CTMCs and induced MMCs in trachea and large airways in antigen-sensitized unchallenged and challenged mice to MCs in skin and helminthic-infected intestine. We found that in the trachea, unlike in skin and intestine, CTMCs and MMCs both express all six serine proteases and CPA3 (mMCP-1(+), -2(+), 4(+)-7(+), CPA3(+)). This phenotype also holds for the lung CTMCs in the proximal bronchi, whereas the induced MMCs express only four proteases, mMCP-1, -2, -6, and -7. Thus, the T-cell-dependent induction of MMCs in trachea, large bronchi, and small intestine provides numbers but does not determine the protease phenotype. Furthermore, the CTMCs, which are constitutive, also show striking differences at these tissue sites, supporting the view that the differences in expression are tissue directed and not dependent on inflammation.
HIV Vaccines—where are we going? (1998)

Carole Heilman (Division of AIDS at the National Institutes of Allergy and Infectious Diseases) and David Baltimore (President of the California Institute of Technology) review current research efforts toward developing anti-HIV vaccines. While recognizing the extraordinary challenges involved in developing a vaccine, Heilman and Baltimore stress that important steps have been taken and that as such there is room for optimism.
Detection in capillary electrophoresis (2000)

A review of the four major, on-line, capillary electrophoresis (CE) detection modalities is presented. It is shown that each detection method, fluorescence, absorbance (conventional and nonconventional), electrochemical and refractive index, have distinct advantages and limitations when applied to analysis in a CE format. Various aspects of CE detection are considered and a perspective regarding the applicability of the technique is provided. It is shown that because of widely varying detection limits (ranging from single molecule to 10(-5) M) and detection scheme complexity, the particular application should dictate the selection of detection methodology in CE.
Induction of Fetal Hemoglobin in the Treatment of Sickle Cell Disease (2006)

Reactivation of fetal hemoglobin (HbF) expression is an important therapeutic option in patients with hemoglobin disorders. In sickle cell disease (SCD), an increase in HbF inhibits the polymerization of sickle hemoglobin and the resulting pathophysiology. Hydroxyurea, an inducer of HbF, has already been approved for the treatment of patients with moderate and/or severe SCD. Recent clinical trials with other pharmacological inducers of HbF, such as butyrate and decitabine, have shown considerable promise. In this chapter, we highlight the important clinical trials with pharmacological inducers of HbF, discuss their mechanisms of action and speculate about the future of this therapeutic approach in the treatment of patients with SCD.
Necessity of Establishing Chemical Integrity of Polymorphs of Drug Substance Using a Combination of NMR, HPLC, Elemental Analysis, and Solid-State Characterization Techniques: Case Studies (2013)

Polymorphism is a solid-state phenomenon; hence, solid-state techniques such as XRPD, DSC, and FT-IR are used for characterization. Many a time, only XRPD is used. These techniques ignore the most important aspects, i.e., chemical purity and the chemical integrity of the polymorph, which can be confirmed by techniques such as 1H NMR, HPLC, and elemental analysis. The aim of this article is to emphasize how techniques such as 1H NMR, elemental analysis, and HPLC purity in addition to other solid-state characterization techniques would help to prove that the drug really exists in different polymorphic forms. H1NMR, HPLC, and elemental analysis reveal the formation of different compounds and not polymorphs in the case of pioglitazone·HCl and glyburide. In the cases of irbesartan and ropinirole·HCl use of a single solid-state characterization technique such as XRPD is not enough for establishing the existence of different polymorphic forms.
Differential expression of Fc receptors for IgG by monocytes and granulocytes from neonates and adults (1996)

The immature neonatal immune system is thought to result in increased risk of infection. Receptors for the Fc moiety of IgG (Fc gamma R) are important in antibody-mediated clearance of microbes by granulocytes and monocytes/macrophages. As an approach to understanding their role in neonatal life, we have compared the constitutive expression of the three Fc receptors--Fc gamma RI (CD64), Fc gamma RII (CD32) and Fc gamma RIII (CD16)--by neonatal and adult blood monocytes and granulocytes using quantitative immunofluorescence by flow cytometry. Our results confirm that there is a small subpopulation of Fc gamma RIII-positive monocytes in adult blood, and furthermore show that this is absent or at a low percentage in cord blood samples. However, the main population of cord blood monocytes expresses low, but significantly higher levels of Fc gamma RIII than adult monocytes. No differences were seen in the quantitative expression of Fc gamma RI and Fc gamma RII. Neonatal granulocytes expressed significantly higher levels of both Fc gamma RI and Fc gamma RII but significantly lower levels of Fc gamma RIII. The data are discussed in terms of the possible role of cytokines and susceptibility to infection.
ASCT-1 Is a Neutral Amino Acid Exchanger with Chloride Channel Activity (1996)

The ubiquitous transport activity known as system ASC is characterized by a preference for small neutral amino acids including alanine, serine, and cysteine. ASCT-1 and ASCT-2, recently cloned transporters exhibiting system ASC-like selectivity, are members of a major amino acid transporter family that includes a number of glutamate transporters. Here we show that ASCT1 functions as an electroneutral exchanger that mediates negligible net amino acid flux. The electrical currents previously shown to be associated with ASCT1-mediated transport result from activation of a thermodynamically uncoupled chloride conductance with permeation properties similar to those described for the glutamate transporter subfamily. Like glutamate transporters, ASCT1 activity requires extracellular Na+. However, unlike glutamate transporters, which mediate net flux and complete a transport cycle by countertransport of K+, ASCT-1 mediates only homo- and heteroexchange of amino acids and is insensitive to K+. The properties of ASCT-1 suggest that it may function to equilibrate different pools of neutral amino acids and provide a mechanism to link amino acid concentration gradients.