gebhart/patrepeval huggingface dataset:
Imiquimod and the imidazoquinolones: mechanism of action and therapeutic potential (2002)

A central development of the past decade has been in our understanding of the interactions between, and interdependence of, the innate and adaptive immune responses. Innate immunity recognizes 'danger' signals and activates adaptive immunity in a targeted, appropriate and effective response. Dendritic cells and macrophages have a central role in this process, and pharmacological agents that modulate the functions of these cells could have therapeutic value. The imidazoquinolone compounds, of which imiquimod, formulated as Aldara trade mark, is the best characterized to date, are such molecules. Imiquimod and its homologues act by activating macrophages and other cells via binding to cell surface receptors, such as Toll receptor 7, thereby inducing secretion of pro-inflammatory cytokines, predominantly interferon (IFN)-alpha, tumour necrosis factor (TNF)-alpha and interleukin (IL)-12. This locally generated cytokine milieu biases towards a Th1 cell mediated immune response with the generation of cytotoxic effectors, and this has been exploited clinically in the treatment of viral infections (human papillomavirus, herpes simplex virus, molluscum contagiosum) and nonmelanoma skin cancer. Imiquimod has been shown to be significantly more effective than placebo in clearing genital warts, and mechanism of action studies indicate that this is related to the ability to generate proinflammatory cytokines and a Th1 response. Intra-epithelial neoplasms of cutaneous and mucosal surfaces are associated with human papillomavirus infection and there is some evidence that immune response modifiers may have therapeutic value for these lesions. Topical immunotherapy with immunomodulators shows potential for effective and patient-friendly treatment of cutaneous viral infections. These compounds also have adjuvant properties that could significantly enhance conventional vaccine strategies.
An application of clustering for strategic group analysis (1985)

Abstract Taxonomies, factor analysis and clustering are discussed as tools to investigate the structure of competitors within an industry (‘strategic groups’). An example using cluster analysis is presented as one means of operationalizing this concept. Careful definition and selection of the dimensions used to identify the boundaries between strategic groups (their mobility barriers) are particularly crucial in the effective application of analytical tools.
Phosphoprotein inhibition of hydroxyapatite dissolution. (1982)

A chromatography column containing hydroxyapatite beads was used to study the effect of different proteins on the rate of hydroxyapatite dissolution. The four phosphoproteins tested (phosvitin, alpha sl-casein, beta-casein and kappa-casein) markedly reduced the rate of hydroxyapatite dissolution. Three nonphosphorylated proteins had a relatively smaller effect. The effect of the protein in reducing the hydroxyapatite dissolution rate has been attributed to protein binding to the surface of hydroxyapatite. The reduction in dissolution rate, expressed as the change in nmol calcium released per min per nmol of phosphoprotein bound to hydroxyapatite, increased with increasing number of phosphoserine residues of the protein. The results are consistent with the proposition that phosphoproteins have a regulatory role in mineralization processes and could provide a mechanism by which dietary and salivary phosphoproteins exert an anticariogenic effect.
All sibdgenomic mRNAs of equine arteritis virus contain am common leader sequence (1990)

During the replication of equine arteritis virus (EAV) six subgenomic mRNAs are synthesized. We present evidence that the viral mRNAs form a 3'-coterminal nested set and contain a common leader sequence of 208 nucleotides which is encoded by the 5'-end of the genome. The leader is joined to the bodies of mRNA 5 and 6 at positions defined by the sequence 5' UCAAC 3'. The part of the leader sequence flanking the UCAAC motif is very similar to the 5'-splice site of the Tetrahymena pre-rRNA. A possible internal guide sequence has been identified 43 nucleotides downstream of the leader sequence on the genome. Hybridization analysis shows that all EAV intracellular RNAs contain the leader sequence. These data imply that the viral subgenomic mRNAs are composed of leader and body sequences which are non-contiguous on the genome.
Propose-and-Attend Single Shot Detector (2019)

We present a simple yet effective prediction module for a one-stage detector. The main process is conducted in a coarse-to-fine manner. First, the module roughly adjusts the default boxes to well capture the extent of target objects in an image. Second, given the adjusted boxes, the module aligns the receptive field of the convolution filters accordingly, not requiring any embedding layers. Both steps build a propose-and-attend mechanism, mimicking two-stage detectors in a highly efficient manner. To verify its effectiveness, we apply the proposed module to a basic one-stage detector SSD. Our final model achieves an accuracy comparable to that of state-of-the-art detectors while using a fraction of their model parameters and computational overheads. Moreover, we found that the proposed module has two strong applications. 1) The module can be successfully integrated into a lightweight backbone, further pushing the efficiency of the one-stage detector. 2) The module also allows train-from-scratch without relying on any sophisticated base networks as previous methods do.
Structure and function of apolipoprotein A-I and high-density lipoprotein (2000)

Structural biology and molecular modeling have provided intriguing insights into the atomic details of the lipid-associated structure of the major protein component of HDL, apo A-I. For the first time, an atomic resolution map is available for future studies of the molecular interactions of HDL in such biological processes as ABC1-regulated HDL assembly, LCAT activation, receptor binding, reverse lipid transport and HDL heterogeneity. Within the context of this paradigm, the current review summarizes the state of HDL research.
A Hydrophobic Transmembrane Segment at the Carboxyl Terminus of thy-1 (1985)

The mode of integration of the glycoprotein thy-1 within the cell membrane has been controversial due to an apparent lack of a transmembrane hydrophobic segment. Rat and mouse complementary DNA and genomic clones encoding the thy-1 molecule have been isolated and sequenced. These studies have enabled us to determine the intron-exon organization of the thy-1 gene. Furthermore, they have revealed the existence of a sequence which would encode an extra segment (31 amino acids) at the carboxyl terminus of the thy-1 molecule. These extra amino acids include a 20-amino acid hydrophobic segment which may be responsible for integration of thy-1 within the plasma membrane.
Retinal transplantation: progress and problems in clinical application (2003)

There is currently no real treatment for blinding disorders that stem from the degeneration of cells in the retina and affect at least 50 million individuals worldwide. The excitement that accompanied the first studies showing the potential of retinal cell transplantation to alleviate the progress of blindness in such diseases as retinitis pigmentosa and age-related macular degeneration has lost some of its momentum, as attempts to apply research to the clinic have failed so far to provide effective treatments. What these studies have shown, however, is not that the approach is flawed but rather that the steps that need to be taken to achieve a viable, clinical treatment are many. This review summarizes the course of retinal transplant studies and points to obstacles that still need to be overcome to improve graft survival and efficacy and to develop a protocol that is effective in a clinical setting. Emphasis is given particularly to the consequences of introducing transplants to sites that have been considered immunologically privileged and to the role of the major histocompatibility complex classes I and II molecules in graft survival and rejection.
Continuous-time MOSFET-C filters in VLSI (1986)

The desirable features of fully integrated, VLSI-compatible continuous-time filters are discussed. A recently proposed integrated continuous-time filtering technique is reviewed, in which MOS transistors are used in place of resistors along with nonlinearity cancellation and on-chip automatic tuning. The filters obtained using this technique are compared to switched-capacitor (SC) filters, digital filters, and continuous-time filters using different techniques. Representative experimental results are given, demonstrating the high performance that can be achieved.
Inhibitory cytokines and cytokine inhibitors (1995)

Cytokines such as interleukin-1 and tumor necrosis factor are involved in the triggering of the immune response, induction of acute inflammatory events, and transition to, or persistence of, chronic inflammation. The action of proinflammatory cytokines is regulated by their receptor expression, downregulation and shedding, by specific inhibitors, and by inhibitory cytokines mainly produced by lymphocytes. This review aims to pinpoint recent findings in the assessment of the biologic activities of cytokine inhibitors and inhibitory cytokines. The suitability of these agents as therapeutic tools is discussed.
Decreased selenium levels in acute myocardial infarction (1989)

To study the association between selenium status and the risk of myocardial infarction, we compared plasma, erythrocyte, and toenail selenium levels and the activity of erythrocyte glutathione peroxidase among 84 patients with acute myocardial infarction and 84 population controls. Mean concentrations of all selenium measurements were lower in cases than controls. The differences were statistically significant, except for the plasma selenium level. A positive trend in the risk of acute myocardial infarction from high to low toenail selenium levels was observed, which persisted after adjustment for other risk factors for myocardial infarction. In contrast, erythrocyte glutathione peroxidase activity was significantly higher in cases than controls (31.3 ± 8.4 U/g of hemoglobin and 28.0 ±8.1 U/g of hemoglobin, respectively). Because the toenail selenium level reflects blood levels up to one year before sampling, these findings suggest that a low selenium status was present before the infarction and, thus, may be of etiologic relevance. The higher glutathione peroxidase activity in the cases may be interpreted as a defense against increased oxidant stress either preceding or following the acute event. (<i>JAMA</i>1989;261:1161-1164)
A Potent Synthetic LXR Agonist Is More Effective than Cholesterol Loading at Inducing ABCA1 mRNA and Stimulating Cholesterol Efflux (2002)

The LXR nuclear receptors are intracellular sensors of cholesterol excess and are activated by various oxysterols. LXRs have been shown to regulate multiple genes of lipid metabolism, including ABCA1 (formerly known as ABC1). ABCA1 is a lipid pump that effluxes cholesterol and phospholipid out of cells. ABCA1 deficiency causes extremely low high density lipoprotein (HDL) levels, demonstrating the importance of ABCA1 in the formation of HDL. The present work shows that the acetyl-podocarpic dimer (APD) is a potent, selective agonist for both LXRalpha (NR1H3) and LXRbeta (NR1H2). In transient transactivation assays, APD was approximately 1000-fold more potent, and yielded approximately 6-fold greater maximal stimulation, than the widely used LXR agonist 22-(R)-hydroxycholesterol. APD induced ABCA1 mRNA levels, and increased efflux of both cholesterol and phospholipid, from multiple cell types. Gas chromatography-mass spectrometry measurements demonstrated that APD stimulated efflux of endogenous cholesterol, eliminating any possible artifacts of cholesterol labeling. For both mRNA induction and stimulation of cholesterol efflux, APD was found to be more effective than was cholesterol loading. Taken together, these data show that APD is a more effective LXR agonist than endogenous oxysterols. LXR agonists may therefore be useful for the prevention and treatment of atherosclerosis, especially in the context of low HDL levels.
RNA nanoparticle as a vector for targeted siRNA delivery into glioblastoma mouse model (2015)

Systemic siRNA administration to target and treat glioblastoma, one of the most deadly cancers, requires robust and efficient delivery platform without immunogenicity. Here we report newly emerged multivalent naked RNA nanoparticle (RNP) based on pRNA 3-way-junction (3WJ) from bacteriophage phi29 to target glioblastoma cells with folate (FA) ligand and deliver siRNA for gene silencing. Systemically injected FA-pRNA-3WJ RNPs successfully targeted and delivered siRNA into brain tumor cells in mice, and efficiently reduced luciferase reporter gene expression (4-fold lower than control). The FA-pRNA-3WJ RNP also can target human patient-derived glioblastoma stem cells, thought to be responsible for tumor initiation and deadly recurrence, without accumulation in adjacent normal brain cells, nor other major internal organs. This study provides possible application of pRNA-3WJ RNP for specific delivery of therapeutics such as siRNA, microRNA and/or chemotherapeutic drugs into glioblastoma cells without inflicting collateral damage to healthy tissues.
Non‐invasive imaging of adaptive immunity using positron emission tomography (2008)

Non-invasive monitoring of adaptive immunity in infection, cancer, and autoimmunity remains a major challenge. Current techniques to monitor lymphocytes involve numeric and functional determinations of immune cells isolated from the peripheral blood (most often) and tissue (rarely). Invasive measurements are prone to sampling errors and are poorly reflective of the dynamic changes in the location, number, and movement of lymphoid cells. These limitations indicate the need for non-invasive whole-body imaging methodologies that allow longitudinal, quantitative, and functional analyses of the immune system in vivo. Positron emission tomography (PET), a clinically based whole-body imaging modality, has the potential to revolutionize diagnostics and therapeutic monitoring in both clinical and pre-clinical settings. This review discusses studies using PET to image adaptive immune responses in small animal models. We address the challenges inherent in assessing whole-body immunity with PET and recent developments that can improve its performance. Finally, we discuss work to translate PET immune imaging into clinical practice.
DNA Microarrays: A Molecular Cloning Manual (2003)

ADVERTISEMENT RETURN TO ISSUEPREVBooks in ReviewNEXTDNA Microarrays: A Molecular Cloning ManualCite this: J. Proteome Res. 2003, 2, 1, 101Publication Date (Web):February 3, 2003Publication History Published online3 February 2003Published inissue 1 February 2003https://doi.org/10.1021/pr030764oRIGHTS & PERMISSIONSArticle Views323Altmetric-Citations-LEARN 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 InReddit PDF (1 MB) Get e-AlertsSUBJECTS:Genetics,Microarrays Get e-Alerts
Influence of cis-diamminedichloroplatinum(II) on DNA synthesis and cell cycle progression in excision repair proficient and deficient Chinese hamster ovary cells. (1988)

DNA has been implicated as the critical intracellular target for cis-diamminedichloroplatinum(II) (cis-DDP) action. Inhibition of DNA synthesis is a consequence of platination and has become accepted as the critical step in cis-DDP-induced toxicity. We have previously demonstrated that, following incubation with cis-DDP, murine leukemia L1210 cells progress through synthesis only to arrest in the G2 phase of the cell cycle. The G2 arrest was transient at low drug concentrations and was persistent at higher concentrations with a concomitant loss of viability. Chinese hamster ovary cell lines both proficient and deficient for DNA excision repair have been used to analyze the relationship between inhibition of DNA synthesis and toxicity and to determine whether DNA repair is necessary for cell cycle progression. Two repair-deficient cell lines were hypersensitive to cis-DDP and demonstrated a marked arrest in the G2 phase. The arrest was transient over only a small range of concentrations. At higher concentrations, the arrest was persistent and the cells subsequently died. Incorporation of [3H]thymidine into macromolecules demonstrated no inhibition of DNA synthesis while these cells progressed through the S phase. In contrast, at higher, but nontoxic, concentrations of cis-DDP, the repair-proficient cells exhibited inhibition of DNA synthesis while in S. At toxic concentrations, these cells also arrested in G2. Therefore, direct inhibition of DNA synthesis correlated only with the concentration of drug and not with the different sensitivities of the cell lines. Arrest of cells in G2 did correlate with toxicity. In every cell line, the appearance of G2-arrested cells preceded cell disintegration. It is proposed that the G2-arrested cells preceded cell disintegration. It is proposed that the G2 arrest results from the inability of the cells to transcribe genes required for passage into mitosis. Cells proficient in DNA repair can circumvent this arrest by repairing the damaged DNA and permitting transcription to proceed. These results support the hypothesis that inhibition of DNA synthesis is not the critical step in cis-DDP-induced cytotoxicity.
From Malaria to Chemokine Receptor: The Emerging Physiologic Role of the Duffy Blood Group Antigen (1997)

ONE OF THE MOST notable achievements of biomedical research in the first half of this century was the identification of red blood cell (RBC) antigens and the recognition of their importance to transfusion medicine and hemolytic disease of the newborn.[1][1] [2][2] These discoveries gave rise to an
Temporal Indication of Marijuana Use Can Be Estimated From Plasma and Urine Concentrations of 9-Tetrahydrocannabinol, 11-Hydroxy- 9-Tetrahydrocannabinol, and 11-Nor- 9-Tetrahydrocannabinol-9-Carboxylic Acid (2001)

Current technology establishes marijuana use based upon detection of the pharmacologically inactive cannabinoid metabolite (11-nor-delta9-carboxy-tetrahydrocannabinol-9-carboxylic acid, THC-COOH) in urine. No accurate prediction of time of use is possible because THC-COOH has a half-life of 6 days. To determine if a temporal relationship between marijuana use and metabolite excretion patterns could be established, eight healthy user-volunteers (18-35 years old) smoked marijuana cigarettes containing 0% (placebo), 1.77%, and 3.58% delta9-tetrahydrocannabinol (THC). Plasma and urine were collected prior to smoking, 5 min after smoking, and hourly thereafter for 8 h for measurement of cannabinoid concentrations by gas chromatography-mass spectrometry. Mathematical models proposed for determination of recent marijuana use were applied to data from this study and verified the temporal use of marijuana. One subject, who later admitted chronic marijuana use (urine baseline THCCOOH, 529.2 ng/mL; plasma, 75.5 ng/mL), excreted 8beta-dihydroxy-THC, peaking 2 h postsmoking (92.3 ng/mL). Urinary THC, the psychoactive component of marijuana, concentrations peaked 2 h after smoking and declined to assay limit of detection (LOD) (1.5 ng/mL) by 6 h. 11-Hydroxy-delta9-tetrahydrocannabinol (11-OH-THC) and THCCOOH were detectable for the entire 8-h testing period but continued to decrease. Urinary concentrations of THC greater than 1.5 ng/mL suggests marijuana use during the previous 8-h time period.
Real and Imaginary Properties of Epsilon-Near-Zero Materials (2016)

From the fundamental principle of causality we show that epsilon-near-zero (ENZ) materials with a very low (asymptotically zero) intrinsic dielectric loss do necessarily possess a very low (asymptotically zero) group velocity of electromagnetic wave propagation. This leads to the loss function being singular and causes high nonradiative damping of the optical resonators and emitters (plasmonic nanoparticles, quantum dots, chromophore molecules) embedded into them or placed at their surfaces. Rough ENZ surfaces do not exhibit hot spots of local fields suggesting that surface modes are overdamped. Reflectors and waveguides also show very large losses both for realistic and idealized ENZ materials.
Trends in male contraception (2003)

Methods that are available for male contraception, namely coitus interruptus, condoms, and vasectomy, have been used since the 19th century. With the exceptions of a few improvements of these methods, no major progress has been made with respect to introducing new male contraceptives since then. It is extremely urgent to develop new, safe, effective, and reversible male contraceptive methods. Among all male contraceptive methods that are being investigated, the hormonal approach is the closest to clinical application. Hormonal contraception provides pregnancy protection by means of spermatogenic suppression. Androgen-progestin regimens currently represent the best available hormonal combination for induction of a profound suppression of spermatogenesis. Further development of new steroids is mandatory for increasing the choices of available contraceptive formulations and to optimize long-term safety of these regimens.
Molecular Neuropathology of TDP-43 Proteinopathies (2009)

The identification of TDP-43 as the major component of the pathologic inclusions in most forms of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS) resolved a long-standing enigma concerning the nature of the ubiquitinated disease protein under these conditions. Anti-TDP-43 immunohistochemistry and the recent development of novel tools, such as phosphorylation-specific TDP-43 antibodies, have increased our knowledge about the spectrum of pathological changes associated with FTLD-U and ALS and moreover, facilitated the neuropathological routine diagnosis of these conditions. This review summarizes the recent advances in our understanding on the molecular neuropathology and pathobiology of TDP-43 in FTLD and ALS.