gebhart/patrepeval huggingface dataset:
Chemical Modifications Rescue Off-Target Effects of RNAi (2006)

RNAi's specificity has been questioned for some time. Three recent papers show that off-target effects should be considered normal, but one paper also provides insight on how chemical modifications of siRNAs may overcome the problem.
Update of hormonal treatment in cancer of the prostate (1993)

Prostate carcinomas are heterogeneous tumors composed of hormone sensitive and hormone insensitive cells. Although all androgens have an effect on prostatic cells, it is believed that dihydrotestosterone (DHT) is the active metabolite primarily utilized by prostatic cancer cells for growth and division. Hormonal therapies are therefore designed to lower tissue levels of DHT or prevent its binding to receptors on prostatic cancer cells. The Veterans Administration Cooperative studies in the 1960s and 1970s laid the groundwork for the use and timing of hormonal therapy. Until recently orchiectomy and estrogens were the two main alternatives, but new compounds such as luteinizing hormone releasing hormone analogs and antiandrogens have shown to be as effective and less toxic than estrogens. Today, important controversies concerning the selection of the best primary treatment and the timing of initiating the hormonal therapy still exist. Second line hormonal strategies are used, but they still have to prove their impact on overall survival.
Polysaccharide Krestin Is a Novel TLR2 Agonist that Mediates Inhibition of Tumor Growth via Stimulation of CD8 T Cells and NK Cells (2010)

These results demonstrate that PSK, a natural product commonly used for the treatment of cancer, is a specific TLR2 agonist and has potent antitumor effects via stimulation of both innate and adaptive immune pathways.
A Concise Update on the Applications of Chiral Ferrocenyl Phosphines in Homogeneous Catalysis Leading to Organic Synthesis (2003)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA Concise Update on the Applications of Chiral Ferrocenyl Phosphines in Homogeneous Catalysis Leading to Organic SynthesisThomas J. ColacotView Author Information Organometallic Chemicals & Catalysts Development, Johnson Matthey Catalysts, 2001 Nolte Drive, West Deptford, New Jersey 08066 Cite this: Chem. Rev. 2003, 103, 8, 3101–3118Publication Date (Web):July 29, 2003Publication History Received11 February 2003Published online29 July 2003Published inissue 1 August 2003https://pubs.acs.org/doi/10.1021/cr000427ohttps://doi.org/10.1021/cr000427oresearch-articleACS PublicationsCopyright © 2003 American Chemical SocietyRequest reuse permissionsArticle Views3867Altmetric-Citations477LEARN 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:Catalysts,Chirality,Group 15 compounds,Hydrogenation,Ligands Get e-Alerts
Identification and Control of Nonlinear Systems Using Fuzzy Hammerstein Models (2000)

This paper addresses the identification and control of nonlinear systems by means of Fuzzy Hammerstein (FH) models, which consist of a static fuzzy model connected in series with a linear dynamic model. For the identification of nonlinear dynamic systems with the proposed FH models, two methods are proposed. The first one is an alternating optimization algorithm that iteratively refines the estimate of the linear dynamics and the parameters of the static fuzzy model. The second method estimates the parameters of the nonlinear static model and of the linear dynamic model simultaneously by using a constrained recursive least-squares algorithm. The obtained FH model is incorporated in a model-based predictive control scheme and a new constraint-handling method is presented. A simulated water-heater process is used as an illustrative example. A comparison with an affine neural network and a linear model is given. Simulation results show that the proposed FH modeling approach is useful for modular parsimonious modeling and model-based control of nonlinear systems.
GTP-dependent association of Raf-1 with Ha-Ras: identification of Raf as a target downstream of Ras in mammalian cells. (1993)

Ras is involved in signal transduction of various factors for growth, differentiation, and oncogenesis. Recent studies have revealed several proteins that function upstream and downstream of the Ras signaling pathway. However, its immediate downstream target molecular has not yet been identified. In an effort to identify the Ras-associated downstream proteins, we added recombinant Ha-Ras in a GTP-bound form to cell-free lysates and used several antibodies against Ras to immunoprecipitate Ras complexes. We found that a serine/threonine kinase, Raf-1, was coimmunoprecipitated with Ha-Ras by two anti-Ras antibodies (LA069 and Y13-238), whereas a neutralizing antibody against Ras (Y13-259) could not precipitate Raf-1. The coimmunoprecipitation was observed with a complex of Ras and guanosine 5'-[gamma- thio]triphosphate but not with a complex of Ras and guanosine 5'-[beta-thio]diphosphate. The GTP-dependent association of Ha-Ras with Raf-1 was observed with lysates of various types of cultured cells, including NIH 3T3, pheochromocytoma (PC) 12, Ba/F3, and Jurkat T cells, and also with crude extracts from rat brain. Furthermore, Raf-1 was precipitated with a transforming Ha-Ras mutant ([Val12]Ras) and wild-type Ha-Ras but not with an effector-region mutant ([Leu35,ARg37]Ras) that lacks transforming activity. These results indicate that Ras.GTP physically associates with Raf either directly or through other component(s) and strongly suggest that Raf functions in close downstream proximity to Ras in mammalian cells.
Genetic engineering -- 1986 (2011)

Item consists of a digitized copy of a video recording of a Vancouver Institute lecture given by Michael Smith on February 15, 1986. Original video recording available in the University Archives (UBC VT 102).
Ghrelin: much more than a natural growth hormone secretagogue. (2002)

Ghrelin, a 28 amino acid acylated peptide predominantly produced by the stomach, displays strong growth hormone-releasing activity mediated by the hypothalamus-pituitary GH secretagogue receptors that were found to be specific for a family of synthetic, orally active GH secretagogues. The discovery of ghrelin brings us to a new understanding of the regulation of GH secretion. However, ghrelin is much more than simply a natural GH secretagogue. It also acts on other central and peripheral receptors and exhibits other actions, including stimulation of lactotroph and corticotroph secretion, orexigenic, influences gastroenteropancreatic functions, and has metabolic, cardiovascular and antiproliferative effects. Knowledge of the whole spectrum of biologic activities of this new hormone will provide new understanding of some critical aspects of neuroscience, metabolism and internal medicine. In fact, GHS were born more than 20 years ago as synthetic molecules, eliciting the hope that orally active GHS could be used to treat GH deficiency as an alternative to recombinant human GH. However, the dream did not become reality and the usefulness of GHS as an anabolic anti-aging intervention restoring the GH/IGF-I axis in somatopause is still unclear. Instead, we now face the theoretic possibility that GHS analogues acting as agonists or antagonists could become candidate drugs for the treatment of pathophysiologic conditions in internal medicine totally unrelated to disorders of GH secretion.
In vitro transformation of the Fusarium mycotoxins deoxynivalenol and zearalenone by the normal gut microflora of pigs (1994)

The biotransformation of the Fusarium mycotoxins deoxynivalenol and zearalenone by the normal bacterial gut flora of pigs was examined in this in vitro study. For that purpose, suspensions of intestinal contents (duodenum, jejunum, caecum, colon, rectum) of porcine origin were incubated anaerobically with deoxynivalenol (DON) or zearalenone (ZEA). DON and ZEA were degraded by the flora of the caudal segments (caecum, colon, rectum) of the gut--particularly the colon content--whereas the microorganisms of the cranial segments (duodenum, jejunum) exhibited no transforming activity. DON was showed to be deepoxidated, ZEA was hydrolyzed to alpha-zearalenol and an unknown metabolite. The transformation of DON was correlated with a loss of cytotoxicity, which could be demonstrated in the MTT(3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium++ + bromide)-cell-culture assay using swine kidney cells as target cells. The results of the study presented here correspond with the data found in in vivo studies. On the basis of these findings one could conclude that this in vitro method seems to be well suited to the study of the transformation of mycotoxins by the microflora of the gut. The in vitro study is cheaper than a feeding trial, and the preliminary information on the metabolism of mycotoxins obtained in such studies is helpful in designing feeding trials more clearly. Besides the simple and fast handling, reproducibility and the protection of the animals studied are further advantages of this in vitro method. In connection with the MTT-cell-culture assay, additional information about the cytotoxic potential of the bacterial transformation products can be obtained.
An electrochemical approach for the detection of HIV-1 protease (2007)

An electrochemical biosensor with a new bioorganometallic approach for the detection of human immunodeficiency virus (HIV) type 1 protease (HIV-1 PR) using surface-bound ferrocenoyl (Fc)-pepstatin conjugates is presented.
A Multithreaded Soft Processor for SoPC Area Reduction (2006)

The growth in size and performance of field programmable gate arrays (FPGAs) has compelled system-on-a-programmable-chip (SoPC) designers to use soft processors for controlling systems with large numbers of intellectual property (IP) blocks. Soft processors control IP blocks, which are accessed by the processor either as peripheral devices or/and by using custom instructions (CIs). In large systems, chip multiprocessors (CMPs) are used to execute many programs concurrently. When these programs require the use of the same IP blocks which are accessed as peripheral devices, they may have to stall waiting for their turn. In the case of CIs, the FPGA logic blocks that implement the CIs may have to be replicated for each processor. In both of these cases FPGA area is wasted, either by idle soft processors or the replication of CI logic blocks. This paper presents a multithreaded (MT) soft processor for area reduction in SoPC implementations. An MT processor allows multiple programs to access the same IP without the need for the logic replication or the replication of whole processors. We first designed a single-threaded processor that is instruction-set compatible to Altera's Nios II soft processor. Our processor is approximately the same size as the Nios II economy version, with equivalent performance. We augmented our processor to have 4-way interleaved multithreading capabilities. This paper compares the area usage and performance of the MT processor versus two CMP systems, using Altera's and our single-threaded processors, separately. Our results show that we can achieve an area savings of about 45% for the processor itself, in addition to the area savings due to not replicating CI logic blocks
Analysis of Mammographic of 1109 of Patients with Breast Cancer (2006)

Objective To improve the mammographic appearance of breast cancer,especially early breast cancer.Methods Datas were derived from review of mammographic studies of 1109 patients with breast cancer from August 1997 to May 2004.Result Among the 1109 cases,66(6%)cases were uninfiltrating carcinoma.74(6.7%)cases were early infiltrating carcinoma.96(8.6%)cases were unusually infiltrating carcinoma and 851(76.7%) usually infiltrate carcinoma.Conclusion Mammography plays a great role in the diagnosis of breast cancer,especially early breast cancer and those with negative result in clinic.
The Multi-Subunit Interleukin-2 Receptor (1989)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Two potential calmodulin-binding sequences in the ryanodine receptor contribute to a mobile, intra-subunit calmodulin-binding domain (2013)

Calmodulin (CaM), a 16 kDa ubiquitous calcium-sensing protein, is known to bind tightly to the calcium release channel/ryanodine receptor (RyR), and modulate RyR function. CaM binding studies using RyR fragments or synthetic peptides have revealed the presence of multiple, potential CaM-binding regions in the primary sequence of RyR. In the present study, we inserted GFP into two of these proposed CaM-binding sequences and mapped them onto the three-dimensional structure of intact cardiac RyR2 by cryo-electron microscopy. Interestingly, we found that the two potential CaM-binding regions encompassing, Arg3595 and Lys4269, respectively, are in close proximity and are adjacent to the previously mapped CaM-binding sites. To monitor the conformational dynamics of these CaM-binding regions, we generated a fluorescence resonance energy transfer (FRET) pair, a dual CFP- and YFP-labeled RyR2 (RyR2R3595-CFP/K4269-YFP) with CFP inserted after Arg3595 and YFP inserted after Lys4269. We transfected HEK293 cells with the RyR2R3595-CFP/K4269-YFP cDNA, and examined their FRET signal in live cells. We detected significant FRET signals in transfected cells that are sensitive to the channel activator caffeine, suggesting that caffeine is able to induce conformational changes in these CaM-binding regions. Importantly, no significant FRET signals were detected in cells co-transfected with cDNAs encoding the single CFP (RyR2R3595-CFP) and single YFP (RyR2K4269-YFP) insertions, indicating that the FRET signal stemmed from the interaction between R3595-CFP and K4269-YFP that are in the same RyR subunit. These observations suggest that multiple regions in the RyR2 sequence may contribute to an intra-subunit CaM-binding pocket that undergoes conformational changes during channel gating.
Lack of HLA class I antigen expression by cultured melanoma cells FO-1 due to a defect in B2m gene expression. (1991)

The melanoma cell line FO-1 does not express HLA class I antigens and does not acquire them on the cell surface after incubation with IFN-gamma. Immunochemical studies showed that FO-1 cells synthesize HLA class I heavy chain, but do not synthesize beta 2-microglobulin (beta 2-mu). The latter abnormality is associated with lack of beta 2-mu mRNA which remains undetectable in FO-1 cells incubated with IFN-gamma. The defect was identified as a genetic lesion in the B2m gene, since DNA hybridization analysis detected a deletion of the first exon of the 5'-flanking region, and of a segment of the first intron of the B2m gene. HLA class I antigen expression was reconstituted on melanoma cells FO-1 after transfection with the wild-type mouse B2m gene, thereby confirming the abnormality of the endogenous B2m gene. The defect identified in FO-1 cells is distinct from that underlying the lack of HLA class I antigen expression by lymphoblastoid cells Daudi, but is remarkably similar to that causing lack of H-2 class I antigen expression by mouse lymphoblastoid cells R1 (TL-). These results suggest that genetic recombination in the 5' region of the B2m gene is a recurrent mechanism in B2m gene defects. In addition to contributing to our understanding of molecular abnormalities in HLA class I antigen expression by melanoma cells, FO-1 cells represent a useful model for analyzing the role of HLA class I antigens in the biology of melanoma cells and in their interaction with cells of the immune system.
Targeting CD73 to improves tumor immunotherapy (131.23) (2010)

Abstract During tumor progression, tumor cells foster a tolerant microenvironment and the activation of many immunosuppressive mechanisms that act in concert to counteract effective immune responses. Therefore, to accomplish cancer immune eradication, tumor-induced immunosuppression must be overcome. We demonstrate that CD73 is widely expressed on many tumor cell lines and upregulated in cancerous tissues with active enzymatic activity. Notably, CD73 expression in malignant cancer patients is closely associated with poor immune status of tumor infiltrating effector T cells. Because CD73 catalyzes AMP breakdown to immunosuppressive adenosine, we propose that CD73-generated adenosine prevents tumor destruction by inhibiting antitumor immunity. We confirmed this hypothesis by showing that inhibition of CD73 by selective inhibitor APCP slowed tumor growth and increased mice survival, and more importantly, augmented CTL therapy of cancer. Using genetic ablation of CD73 on tumor cells by siRNA and CD73 deficient mice, we found that both tumor and host CD73 synergistically controlled tumor progression by impairing antitumor T cell immunity. Thus, counteracting adenosinergic effects of CD73 in the tumor microenvironment represents a novel and feasible strategy of cancer treatment and is complementary to other approaches directed at improving the immune function of antitumor T cells such as adoptive T cell therapy or dendritic cell vaccines.
Pilot study: rapidly cycling hypobaric pressure improves pain after 5 days in adiposis dolorosa (2010)

Adiposis dolorosa (AD) is a rare disorder of painful nodular subcutaneous fat accompanied by fatigue, difficulty with weight loss, inflammation, increased fluid in adipose tissue (lipedema and lymphedema), and hyperalgesia. Sequential compression relieves lymphedema pain; we therefore hypothesized that whole body cyclic pneumatic hypobaric compression may relieve pain in AD. To avoid exacerbating hyperalgesia, we utilized a touch-free method, which is delivered via a high-performance altitude simulator, the Cyclic Variations in Altitude Conditioning™ (CVAC™) process. As a pilot study, 10 participants with AD completed pain and quality of life questionnaires before and after 20-40 minutes of CVAC process daily for 5 days. Participants lost weight (195.5 ± 17.6-193.8 ± 17.3 lb; P = 0.03), and bioimpedance significantly decreased (510 ± 36-490 ± 38 ohm; P = 0.01). There was a significant decrease in scores on the Pain Catastrophizing Scale (P = 0.039), in average (P = 0.002), highest (P = 0.029), lowest (P = 0.04), and current pain severity (P = 0.02) on the Visual Analogue Scale, but there was no change in pain quality by the McGill Pain Questionnaire. There were no significant changes in total and physical SF-36 scores, but the mental score improved significantly (P = 0.049). There were no changes in the Pain Disability Index or Pittsburgh Sleep Quality Index. These data present a potential, new, noninvasive means of treating pain in AD by whole body pneumatic compression as part of the CVAC process. Although randomized, controlled trials are needed to confirm these data, the CVAC process could potentially help in treating AD pain and other chronic pain disorders.
Motion-Tracked Binaural Sound (2004)

A new method is presented for capturing, recording, and reproducing spatial sound that provides a vivid sense of realism. The method generalizes binaural recording, preserving the information needed for dynamic head-motion cues. These dynamic cues greatly reduce the need for customization to the listener. During either capture or recording, the sound field in the vicinity of the head is sampled with a microphone array. During reproduction, a head tracker is used to determine the microphones that are closest to the positions of the listener's ears. Interpolation procedures are used to produce the headphone signals. The properties of different methods for interpolating the microphone signals are presented and analyzed.
Functional topography of discrete domains of human CD38 (2000)

In addition to its catalytic activities as ecto-NAD+ glycohydrolase (NADase), CD38 displays the ability to transduce signals of biological relevance. Indeed, ligation of CD38 on peripheral blood mononuclear cells (PBMC) by agonistic monoclonal antibodies (mAbs) is followed by the transcription and secretion of a vast array of regulatory cytokines. The present work addresses the issue of whether the signals leading to calcium (Ca2+) mobilization, lymphocyte proliferation and release of cytokines is dependent on the epitopes recognized by the individual mAbs. Competition binding analysis identifies two families of mAbs, namely IB4, IB6 and AT2 on one side and OKT10, SUN-4B7 and AT1 on the other. Each mAb family binds epitopes that are completely or partially common. However, the functional activities of the CD38 molecule can not be simply attributed to the epitopes engaged: for instance, IB4 and OKT10 mAbs, which bind different epitopes, perform as agonistic mAbs in inducing PBMC proliferation and interferon (IFN)-gamma secretion. SUN-4B7 yields intermediate effects, whereas IB6, AT1 and AT2 mAbs are totally ineffective. The effects mediated by IB4 and OKT10 mAbs are apparent in 80% of the healthy individuals studied, whereas the effects of SUN-4B7 mAb operate only in 25% of the donors. Interleukin (IL)-6 secretion was observed in all individuals analyzed, irrespective of the epitopes triggered and of mAbs used to ligate the CD38 molecule. In addition, IB4 is the only mAb able to induce significant intracellular Ca2+ fluxes.
Development of a Scleroderma-like Illness during Therapy with L-5-Hydroxytryptophan and Carbidopa (1980)

A scleroderma-like illness developed in a patient treated with L-5 hydroxytryptophan (L-5HTP) and carbidopa for intention myoclonus. The patient had high plasma kynurenine levels that remained high when the L-5HTP-carbidopa combination was discontinued, However, levels rose futher on drug rechallenge, suggesting that the drug unmasked an abnormality in one of the enzymes that catabolize kynurenine. Plasma kynurenine was also determined to be high in seven of 15 patients wth idiopathic scleroderma, but not in eight patients with intention myoclonus treated with L-5HTP and a decarboxylase inhibitor and in whom scleroderma did not develop or in 10 patients with Parkinson's disease treated wth L-dopa and carbidopa. Our data and studies in the literature suggest that two factors may be important in the pathogenesis of some scleroderma-like illness: high plasma serotonin and the abnormality associated with elevated kynurenine.