gebhart/patrepeval huggingface dataset:
Functionalizing Nanoparticles with Biological Molecules: Developing Chemistries that Facilitate Nanotechnology (2013)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTFunctionalizing Nanoparticles with Biological Molecules: Developing Chemistries that Facilitate NanotechnologyKim E. Sapsford†, W. Russ Algar§, Lorenzo Berti⊥, Kelly Boeneman Gemmill‡, Brendan J. Casey†, Eunkeu Oh∥¶, Michael H. Stewart¶, and Igor L. Medintz*‡View Author Information† Division of Biology, Department of Chemistry and Materials Science, Office of Science and Engineering Laboratories, U.S. Food and Drug Administration, Silver Spring, Maryland 20993, United States‡ ‡Center for Bio/Molecular Science and Engineering Code 6900 and ¶Division of Optical Sciences Code 5611, U.S. Naval Research Laboratory, Washington, D.C. 20375, United States§ College of Science, George Mason University, 4400 University Drive, Fairfax, Virginia 22030, United States⊥ Department of Biochemistry and Molecular Medicine, University of California, Davis, School of Medicine, Sacramento, California 95817, United States∥ Sotera Defense Solutions, Crofton, Maryland 21114, United States*E-mail: [email protected]Cite this: Chem. Rev. 2013, 113, 3, 1904–2074Publication Date (Web):February 22, 2013Publication History Received5 April 2012Published online22 February 2013Published inissue 13 March 2013https://pubs.acs.org/doi/10.1021/cr300143vhttps://doi.org/10.1021/cr300143vreview-articleACS PublicationsCopyright © 2013 American Chemical SocietyRequest reuse permissionsArticle Views71277Altmetric-Citations1151LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Chemical biology,Functionalization,Genetics,Peptides and proteins,Quantum dots Get e-Alerts
Two-Component Ferritin Nanoparticles for Multimerization of Diverse Trimeric Antigens (2018)

Antigen multimerization on a nanoparticle can result in improved neutralizing antibody responses. A platform that has been successfully used for displaying antigens from a number of different viruses is ferritin, a self-assembling protein nanoparticle that allows the attachment of multiple copies (24 monomers or 8 trimers) of a single antigen. Here, we design two-component ferritin variants that allow the attachment of two different antigens on a single particle in a defined ratio and geometric pattern. The two-component ferritin was specifically designed for trimeric antigens, accepting four trimers per particle for each antigen, and was tested with antigens derived from HIV-1 envelope (Env) and influenza hemagglutinin (HA). Particle formation and the presence of native-like antigen conformation were confirmed through negative-stain electron microscopy and antibody-antigen binding analysis. Immunizations in guinea pigs with two-component ferritin particles, displaying diverse Env, HA, or both antigens, elicited neutralizing antibody responses against the respective viruses. The results provide proof-of-principle for the self-assembly of a two-component nanoparticle as a general technology for multimeric presentation of trimeric antigens.
The genetics of the mitochondrial DNA of mammalian somatic cells, their hybrids and cybrids. (1978)

A brief review is attempted of the status of the genetics of the mitochondria of mammalian cells in vitro. Reverse segregant human-mouse hybrid strains are unusually stable and retain mitochondrial DNA (mtDNA) of both species for many generations but eventually lose the mtDNA of the species whose chromosomes are segregated. A molecular interchange resembling recombination among mtDNA molecules can be detected in these hybrids. Eisenstadt and co-workers have shown that chloramphenicol inhibits protein synthesis less in mitochondria isolated form chloramphenicol-resistant, mutant cell strains than from sensitive strains. They have also shown that resistance is effectively transmitted by cytoplast fusion. These genetic markers are, therefore, probably in the mtDNA of mammals as they are in yeast. Although chloramphenicol resistance has not been transferred from one distinct species to another by cytoplast fusion, we find that different subspecies of mouse are able to exchange resistance. We have also transferred chloramphenicol resistance to ("transformed") 10(-3) sensitive cells by treating them with purified mtDNA from resistant cells. Treatment with DNA from Escherichia coli and/or mtDNA purified from sensitive cells does not transform. Treatment with nuclear DNA, however, from either sensitive or resistant cells does transform. We suggest that exogenously applied nuclear DNA acts as a potent mutagen in mitochondria. A potential application of the mtDNA transformation phenomenon to molecular cloning of DNA in mammalian mitochondria is proposed.
Denaturant m values and heat capacity changes: Relation to changes in accessible surface areas of protein unfolding (1995)

Denaturant m values, the dependence of the free energy of unfolding on denaturant concentration, have been collected for a large set of proteins. The m value correlates very strongly with the amount of protein surface exposed to solvent upon unfolding, with linear correlation coefficients of R = 0.84 for urea and R = 0.87 for guanidine hydrochloride. These correlations improve to R = 0.90 when the effect of disulfide bonds on the accessible area of the unfolded protein is included. A similar dependence on accessible surface area has been found previously for the heat capacity change (delta Cp), which is confirmed here for our set of proteins. Denaturant m values and heat capacity changes also correlate well with each other. For proteins that undergo a simple two-state unfolding mechanism, the amount of surface exposed to solvent upon unfolding is a main structural determinant for both m values and delta Cp.
Learning Deep Features for Discriminative Localization (2016)

In this work, we revisit the global average pooling layer proposed in [13], and shed light on how it explicitly enables the convolutional neural network (CNN) to have remarkable localization ability despite being trained on imagelevel labels. While this technique was previously proposed as a means for regularizing training, we find that it actually builds a generic localizable deep representation that exposes the implicit attention of CNNs on an image. Despite the apparent simplicity of global average pooling, we are able to achieve 37.1% top-5 error for object localization on ILSVRC 2014 without training on any bounding box annotation. We demonstrate in a variety of experiments that our network is able to localize the discriminative image regions despite just being trained for solving classification task1.
The T cell triggering molecule Tp103 is associated with dipeptidyl aminopeptidase IV activity. (1990)

Tp103 is a 103-kDa T cell activation molecule that defines an alternative activation signal for human T lymphocytes. It is absent from or present in only low amounts on resting T cells but is expressed strongly after activation. Cross-linking of Tp103 via a mAb CB.1 leads to triggering of functional activities in preactivated CD3+ T lymphocytes. By using mAb CB.1 in immunohistology we found that Tp103 is expressed in epithelial cells of various tissues, such as kidney, prostate, epidermis and on endothelia of liver, spleen, lungs, and most vessels, and in bile duct canaliculi in the liver. We found a carcinoma cell line expressing Tp103 and could precipitate a 110-kDa molecule from the surface of these cells. We considered several known molecules of similar distribution and molecular mass for identity with Tp103 and show here that Tp103 is probably identical to the proteolytic enzyme dipeptidyl aminopeptidase IV. When we purified Tp103 by affinity chromatography, typical dipeptidyl aminopeptidase IV activity copurified with Tp103. On activated T cells the enzymatic activity associated with Tp103 is expressed on the outside of the cell. We show that mAb CB.1 recognizes the same molecule as the anti-CD26 mAb anti-Ta1. The anti-Ta1 mAb was found to have T cell-activating activity too, but to differ in its requirements for triggering of T lymphocytes.
Motor Function in Subjects with Mild Cognitive Impairment and Early Alzheimer’s Disease (2005)

Basic mobility, balance, gait and dual-task performance were characterised in 140 consecutive subjects referred to a multidisciplinary university hospital in a geriatric setting for cognitive symptoms and possible dementia. After completion of an extensive diagnostic evaluation, subjects were classified into four diagnostic categories: no cognitive impairment, mild cognitive impairment, Alzheimer's disease (AD) and other dementia. Mean age was 57 +/- 9.2, 60 +/- 7.3, 68 +/- 9.9 and 64 +/- 10.5, respectively. Data on motor function, medication use and presence of white matter changes were evaluated and compared between the diagnostic groups. Motor function seems to be affected in very mild AD but not in mild cognitive impairment, as assessed with performance-based tests. AD subjects were slowed and had difficulties in dual-task performance requiring concurrently performing a cognitive task while walking.
Protein Kinase C-ε Promotes EMT in Breast Cancer (2014)

Protein kinase C (PKC), a family of serine/threonine kinases, plays critical roles in signal transduction and cell regulation. PKCε, a member of the novel PKC family, is known to be a transforming oncogene and a tumor biomarker for aggressive breast cancers. In this study, we examined the involvement of PKCε in epithelial to mesenchymal transition (EMT), the process that leads the way to metastasis. Overexpression of PKCε was sufficient to induce a mesenchymal phenotype in non-tumorigenic mammary epithelial MCF-10 A cells. This was accompanied by a decrease in the epithelial markers, such as E-cadherin, zonula occludens (ZO)-1, and claudin-1, and an increase in mesenchymal marker vimentin. Transforming growth factor β (TGFβ) induced Snail expression and mesenchymal morphology in MCF-10 A cells, and these effects were partially reversed by the PKCε knockdown. PKCε also mediated cell migration and anoikis resistance, which are hallmarks of EMT. Thus, our study demonstrates that PKCε is an important mediator of EMT in breast cancer.
Indium (111In)-Labelled Human Platelets: Optimal Method (1980)

1. A detailed laboratory method is described for the labelling of human platelets with [111In]indium oxine. The 45 min method is simple, requires on 26 ml of blood and is suitable for routine clinical use. 2. After the labelling and resuspension of the platelets in plasma, aggregation responses to both adenosine diphosphate and collagen were similar to those of normal platelet-rich plasma. Less than 5% of the [111In]indium oxine was released by secretory function of platelets. 3. Labelling efficiencies of 90.1 +/- 4.29% (n = 28) were achieved in 60 s by normal concentrations of plasma-free platelet suspensions. 4. Platelet survival in vivo in healthy volunteer subjects follows a linear function with a survival time of 8.44 +/- 0.18 days.
Elevated Levels of the Anti-Inflammatory Interleukin-1 Receptor Antagonist Precede the Onset of Type 2 Diabetes (2008)

Our findings indicate that individuals who will develop type 2 diabetes are characterized by a complex immune activation that also includes upregulation of the anti-inflammatory cytokine IL-1Ra.
Phenotypical and functional characterization of the CD8+ T cell repertoire of HLA-A2.1 transgenic, H-2KbnullDbnull double knockout mice. (1999)

Homozygous HLA-A2.1 transgenic H-2KbnullDbnull double knockout (KO) mice were created. Their potential to develop HLA-A2. 1-restricted cytolytic responses was compared with that of their classical transgenic counterparts, which still express H-2Kb, Db molecules. On cell surfaces, both strains express similar amounts of chimeric (alpha 1 alpha 2 domains of human, alpha 3 cytoplasmic domains of mouse) HLA-A2.1 molecules in noncovalent association with mouse beta 2-microglobulin. Compared with mice that are totally deprived of histocompatibility class Ia molecules (H-2KbnullDbnull double KO), the expression of HLA-A2.1 in transgenic/double KO mice resulted in sizeable increase in the periphery of CD8+ T cells with a normally diversified TCR repertoire. A biased education in favor of HLA-A2.1, ascribable to the absence of H-2 class Ia molecules, was evidenced in these transgenic/double KO mice by their improved capacity to mount HLA-restricted cytolytic responses, regardless of whether they were virally infected or injected with synthetic epitopic peptide. HLA class I transgenic, H-2 class Ia KO mice should represent useful animal models for the preclinical evaluation of vaccine formulations aiming at the induction of HLA class I-restricted CTL responses.
Real-world patterns of pain medication use among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). (2021)

302 Background: Helping patients manage cancer-related pain is an important aspect of supportive care. 80% of patients with mPDAC suffer from abdominal and/or back pain. Pancreatic cancer-related pain is typically treated pharmaceutically using pain medicines, which include opioids or narcotics. Previous studies have found that the presence of pain was associated with impaired survival in pancreatic cancer patients. The goal of this study was to assess the treatment patterns of pain medication usage and their association with duration of therapy (DOT) among patients with mPDAC treated in the real-world setting. Methods: This retrospective observational study utilized the IBM MarketScan Commercial and Medicare supplemental claims data. Data were analyzed for adult patients who were diagnosed with mPDAC and received treatment between January 2015 and March 2020. Patient characteristics and DOT were assessed. Opioid use during treatment including the number of prescriptions filled and average daily dose in morphine equivalents were summarized. Yearly and regional trends of opioid use were assessed. Results: There were 2,841 patients (median age: 61 years, IQR: 56-66) included in the study treated with first line (1L) therapies of interest. 55.6% (n = 1,579) of patients were male and 72.0% (2,046) had commercial insurance. The overall DOT in 1L was 78 days (IQR: 38 – 157). 54.3% of patients filled at least one prescription for opioids during treatment. The mean number of prescriptions filled during treatment was 2.2 (SD: 4.0) and the mean daily dose was 39.5mg morphine equivalents (SD: 134.6) The median DOT among patients who received at least one pain prescription was 92 days (IQR: 44 – 176) while those who did not receive pain medication experienced a DOT of 64 days (IQR: 29 – 135). Among the 1,248 patients who received second line treatment the median DOT was 60.5 days (IQR: 29 – 127). 50.6% (n = 632) filled at least one opioid prescription during treatment. Median DOT among patients who received pain medication was 73.5 days (IQR: 42 – 141) and 47.5 days (IQR: 15 – 103.5) among those who did not. Across lines of therapy opioid use remained stable during the study period ranging from 54.2% among patients treated in 2015 to 51.1% among those who initiated treatment in 2019. No regional differences were observed in prescription patterns within the four US census regions (range: 50.2 – 54.4%). Conclusions: In this real-world cohort of patients with mPDAC nearly half were prescribed at least one opioid during treatment. Patients who received opioids experienced a longer duration of therapy compared to those who did not. Further studies are needed to understand the association of pain control with improved clinical outcomes among patients with mPDAC.
Light-emitting multifunctional rhenium (I) and ruthenium (II) 2,2′-bipyridyl complexes with bipolar character (1999)

A series of multifunctional molecules consisting of hole transport, electron transport, and light-emitting moieties were synthesized and fabricated into single-layer organic light-emitting devices. The light-emitting units were based on 2,2′-bipyridine complexes of rhenium and ruthenium. It was found that, due to the bipolar character of the molecules, the charge carrier mobilities, charge injection barrier, and the device performance were improved. The electron carrier mobilities are on the order of 10−4 cm2 V−1 s−1 and a maximum luminescence of 730 cd/m2 was observed.
Oestrogen-receptor-positive breast cancer: towards bridging histopathological and molecular classifications (2008)

The oestrogen receptor (ER) pathway is key for survival and progression in a significant proportion of breast cancers. The ER can be activated by oestrogen or activated due to "crosstalk" with growth factor receptor pathways. Activated ER signals through transcriptional and non-transcriptional mechanisms. Immunohistochemistry (IHC), in spite of the shortcomings, remains the method of choice as it provides for in situ assessment of ER expression within the tumour cells. This capability is lost in tissue grinding methods that assess oestrogen-binding activity or messenger RNAs in tumours. IHC is also not influenced by the presence of non-tumoural cells or low amounts of tumour cells within samples examined. It is clear that ER-positive tumours do not represent a single entity. Irrespective of the terminology used, low-grade ER-positive (also known as luminal A) tumours need to be differentiated from high-grade/highly proliferative ER-positive tumours. This can be done in a variety of ways including but not limited to analysis of FOXA1 and GATA-3 by IHC, and limited molecular profiling by Oncotype DX, MGH2-gene signature, intrinsic gene signature or MapQuant Dx. Several areas of ER biology are still poorly understood; these include: its function in the cytoplasm/plasma membrane, its role in the differentiation to proliferation switch, and pathways associated with resistance to hormonal therapy. A detailed understanding of these areas will permit better classification and a personalised approach to management of ER-positive breast cancers.
Molecular Cloning, Sequencing, and Heterologous Expression of the vaoA Gene from Penicillium simplicissimum CBS 170.90 Encoding Vanillyl-Alcohol Oxidase (1998)

The cDNA encoding vanillyl-alcohol oxidase (EC 1.1.3.7) was selected from a cDNA library constructed from mRNA isolated from Penicillium simplicissimum CBS 170.90 grown on veratryl alcohol by immunochemical screening. The vaoA-cDNA nucleotide sequence revealed an open reading frame of 1680 base pairs encoding a 560-amino acid protein with a deduced mass of 62,915 Da excluding the covalently bound FAD. The deduced primary structure shares 31% sequence identity with the 8alpha-(O-tyrosyl)-FAD containing subunit of the bacterial flavocytochrome p-cresol methyl hydroxylase. The vaoA gene was isolated from a P. simplicissimum genomic library constructed in lambdaEMBL3 using the vaoA-cDNA as a probe. Comparison of the nucleotide sequence of the vaoA gene with the cDNA nucleotide sequence demonstrated that the gene is interrupted by five short introns. Aspergillus niger NW156 prtF pyrA leuA cspA transformed with the pyrA containing plasmid and a plasmid harboring the complete vaoA gene including the promoter and terminator was able to produce vaoA mRNA and active vanillyl-alcohol oxidase when grown on veratryl alcohol and anisyl alcohol. A similar induction of the vaoA gene was found for P. simplicissimum, indicating that similar regulatory systems are involved in the induction of the vaoA gene in these fungi. Introduction of a consensus ribosome binding site, AGAAGGAG, in the vaoA-cDNA resulted in elevated expression levels of active vanillyl-alcohol oxidase from the lac promoter in Escherichia coli TG2. The catalytic and spectral properties of the purified recombinant enzyme were indistinguishable from the native enzyme.
Temporal sequential logic hardening by design with a low power delay element (2011)

A reduced power delay element for the temporal hardening of sequential digital circuits is presented. The delay element single event transient (SET) tolerance is demonstrated by simulations using it in a radiation hardened by design (RHBD) master slave flip-flop (FF). Using the proposed delay element saves up to 25% total FF power at 50% activity factor. The delay element incorporates redundancy to mask long transients, which would otherwise limit the circuit hardness. Two FF layouts using the proposed delay element are used in synthesis and auto-place and route experiments to confirm overall power, performance, and density. The first (interleaved) version uses a multi-bit cell interleaving the constituent circuits of four FFs. The second (inline) version interleaves the master and slave circuits to achieve high density while maintaining adequate critical node separation. The latter is shown to be more power efficient and the former is more robust to multiple node collection.
Photonic chip–based optical frequency comb using soliton Cherenkov radiation (2016)

Optical solitons are propagating pulses of light that retain their shape because nonlinearity and dispersion balance each other. In the presence of higher-order dispersion, optical solitons can emit dispersive waves via the process of soliton Cherenkov radiation. This process underlies supercontinuum generation and is of critical importance in frequency metrology. Using a continuous wave-pumped, dispersion-engineered, integrated silicon nitride microresonator, we generated continuously circulating temporal dissipative Kerr solitons. The presence of higher-order dispersion led to the emission of red-shifted soliton Cherenkov radiation. The output corresponds to a fully coherent optical frequency comb that spans two-thirds of an octave and whose phase we were able to stabilize to the sub-Hertz level. By preserving coherence over a broad spectral bandwidth, our device offers the opportunity to develop compact on-chip frequency combs for frequency metrology or spectroscopy.
Treatment of menorrhagia. (2007)

Menorrhagia is defined as excessive uterine bleeding occurring at regular intervals or prolonged uterine bleeding lasting more than seven days. The classic definition of menorrhagia (i.e., greater than 80 mL of blood loss per cycle) is rarely used clinically. Women describe the loss or reduction of daily activities as more important than the actual volume of bleeding. Routine testing of all women with menorrhagia for inherited coagulation disorders is unnecessary. Saline infusion sonohysteroscopy detects intracavitary abnormalities such as endometrial polyps or uterine leiomyoma and is less expensive and invasive than hysteroscopy. Endometrial biopsy is effective for diagnosing precancerous lesions and adenocarcinoma but not for intracavitary lesions. Except for continuous progestin, medical therapies are limited. The levonorgestrel-releasing intrauterine device is an effective therapy for women who want to preserve fertility and avoid surgery. Surgical therapies include endometrial ablation methods that preserve the uterus; and hysterectomy, which results in high satisfaction rates but with potential surgical morbidity. Overall, hysterectomy and endometrial ablation result in the greatest satisfaction rates if future childbearing is not desired. Treatment of menorrhagia results in substantial improvement in quality of life.