gebhart/patrepeval huggingface dataset:
The Dendritic Cell System and its Role in Immunogenicity (1991)

Dendritic cells are a system of antigen presenting cells that function to initiate several immune responses such as the sensitization of MHC-restricted T cells, the rejection of organ transplants, and the formation of T-dependent antibodies. Dendritic cells are found in many nonlymphoid tissues but can migrate via the afferent lymph or the blood stream to the T-dependent areas of lymphoid organs. In skin, the immunostimulatory function of dendritic cells is enhanced by cytokines, especially GM-CSF. After foreign proteins are administered in situ, dendritic cells are a principal reservoir of immunogen. In vitro studies indicate that dendritic cells only process proteins for a short period of time, when the rate of synthesis of MHC products and content of acidic endocytic vesicles are high. Antigen processing is selectively dampened after a day in culture, but the capacity to stimulate responses to surface bound peptides and mitogens remains strong. Dendritic cells are motile, and efficiently cluster and activate T cells that are specific for stimuli on the cell surface. High levels of MHC class-I and -II products and several adhesins, such as ICAM-1 and LFA-3, likely contribute to these functions. Therefore dendritic cells are specialized to mediate several physiologic components of immunogenicity such as the acquisition of antigens in tissues, the migration to lymphoid organs, and the identification and activation of antigen-specific T cells. The function of these presenting cells in immunologic tolerance is just beginning to be studied.
Experimental murine and primate models for dissection of the immunosuppressive potential of photochemotherapy in autoimmune disease and transplantation. (1990)

This paper reviews the results achieved in murine and primate models of autoimmune disease and transplantation. These studies have attempted to clarify the nature and specificity of the response induced by reinfusion of phototreated immunoactive lymphocytes. Results obtained in murine lupus have demonstrated that some of the disease features related to the abnormal proliferation of inducer T cells can be inhibited both prophylactically and therapeutically by exposure to photoinactivated autoimmune splenocytes. Radiolabeling studies performed in normal syngeneic mice have shown that, if immunoactive cells are phototreated and injected, their recirculation pattern is altered, and increased sequestration in the spleen, bone marrow, and kidney is noted. These studies suggest that reinfused, phototreated, antigen-activated lymphocytes may localize in sites where they are available for induction of immune responses. Primate cardiac xenotransplantation models have demonstrated that reinfusion of phototreated autologous leukocytes, administered with cyclosporine A and steroids, mediates enhanced specific suppression of both the cellular and humoral host response to foreign tissue. Taken as a whole, the experimental models suggest that photopheresis may provide a means of inducing specific suppression of immunoactive T cells. This form of therapy may have a role as an immunosuppressive agent in both autoimmune disease and transplantation.
Protein degradation by the phosphoinositide-specific phospholipase C-alpha family from rat liver endoplasmic reticulum. (1992)

A 60-kDa protein homologous to phosphoinositide-specific phospholipase C-alpha was purified to apparent homogeneity on sodium dodecyl sulfate-polyacrylamide gel electrophoresis from the rough endoplasmic reticulum of rat liver through three sequential chromatographies on DEAE Toyopearl 650, AF-heparin Toyopearl 650M, and TSK gel G3000SW. The purified protein was monomeric, with an M(r) of 60,000. Eight types of protein were further separated from the 60-kDa protein and named ER60A-ER60H according to the order of their elution from a TSK gel DEAE-5PW column. They were essentially identical in terms of immunochemical properties and the NH2-terminal amino acid sequence. The partial amino acid sequence of ER60F showed homology to that of phosphoinositide-specific phospholipase C-alpha. ER60A-ER60H showed no phosphoinositide-specific phospholipase C activity. However, ER60A-ER60H catalyzed cleavage of themselves and the endoplasmic reticulum proteins protein disulfide-isomerase and calreticulin. Proteolytic degradation was inhibited by p-chloromercuribenzoate. These results indicate that ER60A-ER60H comprise a group of endoplasmic reticulum resident proteins and show thiol group-related proteolytic activity.
Frequency and predictors of loss of response to infliximab or adalimumab in Crohn's disease after one-year treatment period - a single center experience. (2012)

BACKGROUND & AIMS. Secondary loss of response is a frequent event occurring during biological therapy. The aim of this study was to assess loss of efficacy in patients with Crohn's disease treated with infliximab or adalimumab for a year. The secondary goals were to identify clinical or laboratory predictors of loss of response. METHODS. Sixty-one Crohn's disease patients achieved remission after the induction therapy and received regular maintenance therapy: 35 of them were on infliximab, 26 on adalimumab therapy. None of the patients treated with infliximab had received previous biological therapy, and 10 of the adalimumab-treated patients were naïve to biological therapy. The data of patients who relapsed and who remained in remission and also the characteristics of infliximab-treated patients and adalimumab-naïve patients were compared. Data were analyzed statistically. RESULTS. Remission was achieved in 70.5%; response was achieved in 29.5% of the patients after induction. Loss of response occurred in 22 of 61 patients after a year of therapy. The proportion of remission after induction was significantly lower in patients who lost response vs. those who remained in remission. More patients with sustained remission received immunosuppressive therapy before and during the biological therapy vs. those with loss of response. Loss of response was significantly more frequent and occurred earlier in adalimumab-naïve patients vs. infliximab-treated patients. CONCLUSION. The need for dose escalation should be calculated in the budget in the majority of patients, especially in adalimumab-treated patients.
Risk of Death With Atypical Antipsychotic Drug Treatment for Dementia (2005)

Atypical antipsychotic drugs may be associated with a small increased risk for death compared with placebo. This risk should be considered within the context of medical need for the drugs, efficacy evidence, medical comorbidity, and the efficacy and safety of alternatives. Individual patient analyses modeling survival and causes of death are needed.
Biotin‐, Pyrene‐, and GRGDS‐Functionalized Polymers and Nanogels via ATRP and End Group Modification (2008)

Abstract Functionality, one of the key attributes of atom transfer radical polymerization (ATRP), was utilized for the synthesis of well‐controlled polymers functionalized with biotin, pyrene, and peptides. Hydroxy‐functionalized poly(oligo(ethylene oxide) monomethyl ether methacrylate) (HO‐POEOMA) was prepared by AGET ATRP of OEOMA initiated by 2‐hydroxyethyl 2‐bromoisobutyrate in water or in inverse miniemulsion of water/cyclohexane at ambient temperature. HO‐POEOMA was then further functionalized with biotin, pyrene, and GRGDS peptide. In addition, ATRP and click chemistry offered an efficient route for the synthesis of telechelic di‐biotin polymers. These general methods can be applied to the formation of different functional materials conjugated with proteins, dyes, nucleic acids, and drugs. magnified image
Epoxy Ethers. XIX. Reaction of 1,2-Epoxy-1-methoxy-2-methyl-1-phenylpropane with Amines (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEpoxy Ethers. XIX. Reaction of 1,2-Epoxy-1-methoxy-2-methyl-1-phenylpropane with AminesCalvin L. Stevens and Charles Hung ChangCite this: J. Org. Chem. 1962, 27, 12, 4392–4396Publication Date (Print):December 1, 1962Publication History Published online1 May 2002Published inissue 1 December 1962https://pubs.acs.org/doi/10.1021/jo01059a063https://doi.org/10.1021/jo01059a063research-articleACS PublicationsRequest reuse permissionsArticle Views222Altmetric-Citations10LEARN 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 Get e-Alerts
Chitin Induces Natural Competence in Vibrio cholerae (2005)

The mosaic-structured Vibrio cholerae genome points to the importance of horizontal gene transfer (HGT) in the evolution of this human pathogen. We showed that V. cholerae can acquire new genetic material by natural transformation during growth on chitin, a biopolymer that is abundant in aquatic habitats (e.g., from crustacean exoskeletons), where it lives as an autochthonous microbe. Transformation competence was found to require a type IV pilus assembly complex, a putative DNA binding protein, and three convergent regulatory cascades, which are activated by chitin, increasing cell density, and nutrient limitation, a decline in growth rate, or stress.
Outer-Sphere Direction in Iridium C–H Borylation (2012)

The NHBoc group affords ortho selective C-H borylations in arenes and alkenes. Experimental and computational studies support an outer sphere mechanism where the N-H proton hydrogen bonds to a boryl ligand oxygen. The regioselectivities are unique and complement those of directed ortho metalations.
Origin of bistramide a identified in Lissoclinum bistratum (Urochordata): possible involvement of symbiotic Prochlorophyta (1990)

An attempt was made to determine whether bistramide A (=bistratene A), a polycycloether with biological activity isolated from Lissodinum bistratum Sluiter, originates from the ascidian itself or from its symbiont Prochlorophyta. A high-pressure liquid chromatography assay carried out on the whole ascidian, the ascidian without a portion of its Prochloron and the Prochloron themselves gave concentrations respectively of 0.182,0.166 and 0.850%. In view of these results, as well as of the capacity of Prochloron to synthesize complex nitrogenous products and the cytotoxicity of these products, it is hypothesized that bistramide A originates exclusively in Prochloron.
Nuclear Transplantation in Mouse Embryos: Assessment of Nuclear Function1 (1987)

Enucleated mouse zygotes receiving eight-cell nuclei rarely develop beyond the two-cell stage, whereas enucleated two-cell embryos with eight-cell nuclei develop to blastocysts, and a few develop to midgestation. In this study the function of eight-cell nuclei in either the zygote or two-cell recipient was assessed by monitoring several nuclear-dependent events. These included methionine uptake, qualitative changes in protein synthesis, the time of blastocoele formation, and changes in nuclear volume. Although enucleated zygotes with nuclei from eight-cell embryos did not develop past the two-cell stage and had abnormally low levels of methionine uptake, they did show a normal zygote-to-two-cell transition in the types of polypeptides synthesized. Enucleated two-cell embryos with eight-cell nuclei formed blastocysts on schedule with the recipient cell stage and reached levels of methionine uptake equivalent to control embryos. The types of proteins synthesized by two-cell embryos with eight-cell nuclei indicated that the nucleus was developing partly in accord with its own developmental program. Transplanted nuclei did not enlarge to acquire the volume of the recipient cell's nucleus in either the zygote or the two-cell recipient. These results indicate that the difference in development between zygotes and two-cell embryos (each with eight-cell nuclei) may be the result of a greater overlap of function between the two-cell and eight-cell stages, rather than the extent of nuclear reprogramming. Nuclear function was not completely normal in either type of embryo, which may explain their failure to develop to term.
Azathioprine: State of the Art in Inflammatory Bowel Disease (1998)

AZA/6MP therapy is efficacious and reasonably safe for selected patients with IBD. Indications for treatment with AZA/6MP include refractory Crohn's disease, fistulizing Crohn's disease, steroid-dependent Crohn's disease, Crohn's disease remission maintenance, and possibly refractory UC, steroid dependent UC, and UC remission maintenance. The use of these immune modifier drugs in patients with IBD represents a significant therapeutic advance.
TNF in combination with GM-CSF enhances the differentiation of neonatal cord blood stem cells into dendritic cells and macrophages (1992)

We describe dendritic cell progenitors within the CD34+ stem cell compartment in neonatal cord blood and identify growth factors contributing to their differentiation. Granulocyte-macrophage colony-stimulating factor (GM-CSF), although mainly promoting the growth and differentiation of monocyte-macrophages (mono-m psi s), also induced the differentiation of cells with the distinctive morphological features of dendritic cells (DCs). Tumor necrosis factor (TNF) in combination with GM-CSF promoted further growth of both cell types but most notably increased the DC content. In situ analysis revealed that the cells exhibiting DC morphology were positive for class II major histocompatibility complex antigens but were CD14 negative, did not exhibit nonspecific esterase activity, and were nonphagocytic. Moreover, the mixed leukocyte reaction stimulatory capacity of cultures with the higher DC content was greater. TNF, interleukin-1 (IL-1), IL-6, or platelet-derived growth factor (PDGF) was inactive in promoting stem cell proliferation or DC morphology. IL-1 or PDGF synergized with GM-CSF to increase mono-m psi-associated cell proliferation but did not increase the DC content. The development of a common DC-monocyte precursor was suggested by the presence of colony-forming unit-like clusters containing mono-m psi s and DCs and one sharp proliferative peak. The loss of DC morphology after 21 days, coupled with increases in mono-m psi-associated markers and a constant number of viable cells, further suggests that DC morphology may fluctuate in culture or is a transient feature acquired by certain cells of the mono-m psi lineage.
The role of ABC transporters in progression and clinical outcome of colorectal cancer (2012)

Worldwide, colorectal cancer (CRC) is the third most common cancer, with the highest mortality rates occurring in Central Europe. The use of chemotherapy to treat CRC is limited by the inter-individual variability in drug response and the development of cancer cell resistance. ATP-binding cassette (ABC) transporters play a crucial role in the development of resistance by the efflux of anticancer agents outside of cancer cells. The aim of this study was to explore transcript levels of all human ABCs in tumours and non-neoplastic control tissues from CRC patients collected before the first line of treatment by 5-fluorouracil (5-FU)-containing regimen. The prognostic potential of ABCs was evaluated by the correlation of transcript levels with clinical factors. Relations between transcript levels of ABCs in tumours and chemotherapy efficacy were also addressed. The transcript profile of all known human ABCs was assessed using real-time polymerase chain reaction with a relative standard curve. The majority of the studied ABCs were down-regulated or unchanged between tumours and control tissues. ABCA12, ABCA13, ABCB6, ABCC1, ABCC2 and ABCE1 were up-regulated in tumours versus control tissues. Transcript levels of ABCA12, ABCC7 and ABCC8 increased in direction from colon to rectum. Additionally, transcript levels of ABCB9, ABCB11, ABCG5 and ABCG8 followed the reverse significant trend, i.e. a decrease in direction from colon to rectum. The transcript level of ABCC10 in tumours correlated with the grade (P = 0.01). Transcript levels of ABCC6, ABCC11, ABCF1 and ABCF2 were significantly lower in non-responders to palliative chemotherapy in comparison with responders. The disease-free interval of patients treated by adjuvant chemotherapy was significantly shorter in patients with low transcript levels of ABCA7, ABCA13, ABCB4, ABCC11 and ABCD4. In conclusion, ABCC11 may be a promising candidate marker for a validation study on 5-FU therapy outcome.
Heterocyclic compounds. Part 15. NN′-Di-t-butylthiadiaziridine 1,1-dioxide: synthesis and reactions (1977)

An intermediate involved in the conversion of NN′-di-t-butylsulphamide into 2,2-′dimethyl-2,2-′-azopropane has been prepared and found to be a thiadiaziridine 1,1-dioxide. Several reactions of this heterocycle are reported, including hydrolysis, methanolysis, and nucleophilic conversions.
Engineering and optimising deaminase fusions for genome editing (2016)

Precise editing is essential for biomedical research and gene therapy. Yet, homology-directed genome modification is limited by the requirements for genomic lesions, homology donors and the endogenous DNA repair machinery. Here we engineered programmable cytidine deaminases and test if we could introduce site-specific cytidine to thymidine transitions in the absence of targeted genomic lesions. Our programmable deaminases effectively convert specific cytidines to thymidines with 13% efficiency in Escherichia coli and 2.5% in human cells. However, off-target deaminations were detected more than 150 bp away from the target site. Moreover, whole genome sequencing revealed that edited bacterial cells did not harbour chromosomal abnormalities but demonstrated elevated global cytidine deamination at deaminase intrinsic binding sites. Therefore programmable deaminases represent a promising genome editing tool in prokaryotes and eukaryotes. Future engineering is required to overcome the processivity and the intrinsic DNA binding affinity of deaminases for safer therapeutic applications.
Chondrocytes from osteoarthritic cartilage have increased expression of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) and -5, but not IGF-II or IGFBP-4. (1996)

Osteoarthritis is a disease in which articular cartilage metabolism is altered, leading to cartilage destruction. As insulin-like growth factor-I (IGF-I) is the major anabolic mediator for articular cartilage, and the IGF-binding proteins (IGFBPs) are an integral part of the IGF axis, they may play a role in the pathophysiology of osteoarthritis. Chondrocytes isolated from fibrillated and normal appearing areas of osteoarthritic human cartilage and from normal cartilage were studied for IGF and IGFBP expression. IGF and IGFBP messenger ribonucleic acids were analyzed by a RT-quantitative PCR technique and Northern blotting. In osteoarthritic chondrocytes, IGF-I message was increased 3.5-fold, IGFBP-3 was increased 24-fold, and IGFBP-5 was increased 16-fold over normal chondrocytes. Chondrocytes from normal appearing areas of cartilage from osteoarthritic joints had intermediate levels. Message levels for beta-actin, IGF-II, and IGFBP-4 were unchanged between the cartilage types. IGF and IGFBP production were analyzed by Western ligand blots and RIAs of conditioned medium from cartilage cultured in serum-free conditions. IGF-I was undetectable in conditioned medium from normal cartilage and increased in that from osteoarthritic cartilage. Osteoarthritic cartilage samples produced IGFBP-2, -3, and -4; glycosylated IGFBP-4; and IGFBP-5. IGFBP-2, -3, and -5 production was increased in osteoarthritic cartilage. Proteases with activity against IGFBP-3 and -5 were also produced by osteoarthritic cartilage. The observation that IGFBP-3 and -5 expression and production are elevated in osteoarthritic cartilage suggests that they may be acting as a competitor for IGF-I in osteoarthritic cartilage, thus reducing the anabolic stimulation of this tissue and contributing to the net loss of cartilage in this disease.
Biological characterization of preclinical Bioluminescent Osteosarcoma Orthotopic Mouse (BOOM) model: A multi-modality approach (2013)

Osteosarcoma (OS) is a bone malignancy that affects children and adolescents. It is a highly aggressive tumor and typically metastasizes to lungs. Despite aggressive chemotherapy and surgical treatments, the current 5 year survival rate is 60-70%. Clinically relevant models are needed to understand OS pathobiology, metastatic progression from bones to lungs, and ultimately, to develop more efficacious treatment strategies and improve survival rates in OS patients with metastasis. The main goal of this study was to develop and characterize an <i>in vivo</i> OS model that will allow non-invasive tracking of tumor progression in real time, and aid in studying OS pathobiology, and screening of potential therapeutic agents against OS. In this study, we have used a multi-modality approach using bioluminescent imaging, electron microscopy, micro-computed tomography, and histopathology to develop and characterize a preclinical Bioluminescent Osteosarcoma Orthotopic Mouse (BOOM) model, using 143B human OS cell line. The results of this study clearly demonstrate that the BOOM model represents the clinical disease as evidenced by a spectrum of changes associated with tumor establishment, progression and metastasis, and detection of known OS biomarkers in the primary and metastatic tumor tissue. Key novel findings of this study include: (a) multimodality approach for extensive characterization of the BOOM model using 143B human OS cell line; (b) evidence of renal metastasis in OS orthotopic model using 143B cells; (c) evidence of Runx2 expression in the metastatic lung tissue; and (d) evidence of the presence of extracellular membrane vesicles and myofibroblasts in the BOOM model.
Spontaneous Resolution of Racemic Camphorates in the Formation of Three-Dimensional Metal−Organic Frameworks (2009)

Reported here is a rare example of enantioselective processes between organic racemic ligands (DL-camphorates) with in situ formed chiral metal complexes. Such enantioselectivity leads to a double spontaneous resolution of two pairs of distinctly different racemates [the LambdaDelta-Zn(Htea) units and the DL-camphorate ligands] into two chiral three-dimensional frameworks containing only one enantiommeric form from each racemate. This work demonstrates unique enantioselectivity in the self-assembly of metal-organic frameworks containing multiple chiral features, which points to a new avenue for the preparation of chiral framework materials and for the resolution of racemates.
A scalable video compression technique based on wavelet transform and MPEG coding (1999)

We present a scalable coding scheme based on the discrete wavelet transform (DWT) and MPEG coding for video applications. It utilizes the hierarchical pyramid structure that provides multiple resolutions. The DWT decomposes the image into several bands. In each band, a fixed-size motion compensated MPEG coder with custom-designed quantization tables and scanning direction is employed. This scheme has the advantages of reusing the widely available MPEG hardware and software as well as relieving the limitation of the image size imposed by the MPEG hardware technology. The simulation results show that the DWT-MPEG coding method improves the image quality over ordinary MPEG coding by 0.3/spl sim/1.5 dB.