gebhart/patrepeval huggingface dataset:
Immune Intervention in AIDS (2014)

This chapter reviews concepts and strategies that are being considered for the development of effective immune interventions for the treatment of human immunodeficiency virus (HIV) disease. It is likely that the development of effective immune-based interventions for the treatment of HIV infection will be greatly facilitated by an improved understanding of the fundamental mechanisms of the immunopathogenesis of AIDS. An important challenge for future research efforts will be to discover ways of modulating the host immune response so its beneficial aspects are enhanced without simultaneously increasing its deleterious aspects. Similarly, any attempt to use immunosuppression as an approach to abrogation of the deleterious indirect consequences of HIV infection will need to be done in a way that does not also compromise the beneficial aspects of immunemediated control of HIV replication. The idea of therapeutic vaccination of HIVinfected individuals dates back to the early years of the AIDS epidemic, and clinical trials aimed at augmenting anti-HIV cellular immune responses in infected patients by immunization with the recombinant HIV envelope glycoproteins gp120 and gp160 were first performed in the early 1990s. Recent studies of prophylactic DNA vaccine in macaque models of simian immunodeficiency virus (SIV) infection have shown that DNA vaccines, in combination with cytokines (e.g., interleukin-2 [IL-2]) or followed by boosting with recombinant viral vectors (e.g., an attenuated strain of vaccinia virus known as modified vaccinia Ankara), can induce potent anti-HIV CD4+ and CD8+ T-cell responses and enable substantial control of SIV viremia following experimental challenge with virulent virus strains.
Accessing Web Applications with Multiple Context-Aware Devices. (2004)

Current web applications are meant to be accessed from a single device, typically a desktop computer. Single-authoring has been proposed as a solution for allowing web applications to be used from a variety of devices. However, single-authoring does not provide sufficient flexibility to allow a user to roam seamlessly from one device to another. In this paper, we address this problem and present our architecture for allowing access to web applications from a set of federated devices. Our architecture is intended as a general-purpose solution and is able to (i) select the appropriate devices, (ii) synchronize the different views, and (iii) transcode documents as needed. We also present the main features of our implementation of our architecture, including an infrared positioning system which allows us to determine which devices are available to the user. 1
Polyurethane elastomers made from linear polybutadiene diols (2002)

Abstract Segmented polyurethane elastomers made from linear polybutadiene diols terminated with primary (Krasol LBH‐P) or secondary (Krasol LBH) hydroxy groups, alicyclic diisocyanate, and aliphatic chain extender were prepared and tested. The system was chemically crosslinked either through isocyanurate, that is, hexahydro‐1,3,5‐triazine‐2,4,6‐trione groups (formed by catalyzed cyclotrimerization of isocyanate groups), or by low molecular weight triols. The best balance of stress‐strain properties and reasonable thermal stability was obtained for systems in which only a small amount of chemical crosslinks was present in predominantly physically crosslinked networks. The influence of the type of polymer diol, chemical crosslinking, diisocyanate, and technique of preparation on mechanical, thermal, and swelling properties is discussed. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 85: 84–91, 2002
Synthesis of oligodeoxynucleotides containing 2-thiopyrimidine residues - a new protection scheme (1994)

A method is described for the incorporation of 2'-deoxy-2-thiouridine (dS2U) and 2'-deoxy-2-thiothymidine (dS2T) into oligodeoxynucleotides at predetermined positions. This requires N3 or O4-acylation of dS2U and dS2T with toluoyl chloride. These base-protected thiopyrimidines are completely stable toward the aqueous iodine oxidation reagent used in the phosphoramidite DNA synthesis method. The toluoyl protecting group is removed during the standard post-synthetic ammonia treatment. This novel protection strategy allows dS2U and dS2T to be efficiently incorporated into oligodeoxynucleotides at predetermined sites without the usual problem of desulfurization and decomposition. Several 14-mers containing the Eco-RI recognition site (dGGCGGAAXXCCGCC and dGGCGGAAXXCGCGG, where X represents dT, dS2U or dS2T) have been synthesized and characterized by base composition, thermal denaturation, CD spectroscopy and endonuclease substrate activity.
Fundamental Principles and Processes of Pharmacy (1950)

This book is intended as a text for introductory pharmacy. Its purpose is to introduce the student of pharmacy to the professional subjects he will study in his academic program. The first 132 pages are devoted to what may be termed "background information" of the profession of pharmacy including: its historical development, its ethical principles, the pharmaceutic curriculum, opportunities in the profession and essential pharmaceutic literature. The material in the six chapters encompassing these pages is presented in a clear, concise and interesting manner and gives the beginning student a splendid orientation with the past, the present and the probable future of his profession. Indeed, this concise condensation could be reviewed to advantage by present day practitioners of pharmacy. It represents a well-thought-out outline which would give to the beginning student a broad vision of the profession he is entering. There is a chapter on the natural products used in
Association Between Plasma Levels of Monocyte Chemoattractant Protein-1 and Long-Term Clinical Outcomes in Patients With Acute Coronary Syndromes (2003)

In a large cohort of patients with acute coronary syndromes, an elevated baseline level of MCP-1 was associated both with traditional risk factors for atherosclerosis as well as an increased risk for death or myocardial infarction, independent of baseline variables. Because it appears to play a crucial role at multiple stages of atherosclerosis, MCP-1 is attractive as a surrogate biomarker and merits further study as a potential therapeutic target.
An Autogeneic Feeder Cell System That Efficiently Supports Growth of Undifferentiated Human Embryonic Stem Cells (2005)

Human embryonic stem cells (hESCs) have great potential as a source of cells for therapeutic uses, but their culture requires the support of mouse or human cells, either directly as a feeder cell layer or indirectly as a source of conditioned medium in feeder-free culture systems. Unfortunately, the risks of cross-transfer of pathogens from xenogeneic or allogeneic feeders or cell by-products limit their medical applications. In addition, not all human feeders support the growth of hESCs equally well, and ethical concerns have been raised regarding the derivation of feeder cells from aborted human fetuses. We report here the culture of hESCs on a novel feeder cell system, comprising fibroblast-like cells derived from the spontaneous differentiation of hESCs. Isogenicity of the hESCs and hESC-derived fibroblasts was confirmed by micro satellite analysis. The nature of the hESC-derived fibroblasts was identified by the expression of specific markers. This feeder system permits continuous growth of undifferentiated and pluripotent hESCs, as demonstrated by the expression of specific hESC markers, by the formation of teratomas after injection of hESCs into severely combined immunodeficient mice, and by in vitro differentiation of hESCs into differentiated cells of ectodermal, endodermal, and mesodermal origin. Feeder cells derived from hESCs offers a potentially more secure autogeneic and genotypically homogenous system for the growth of undifferentiated hESCs.
Multispecies diel transcriptional oscillations in open ocean heterotrophic bacterial assemblages (2014)

Oscillating diurnal rhythms of gene transcription, metabolic activity, and behavior are found in all three domains of life. However, diel cycles in naturally occurring heterotrophic bacteria and archaea have rarely been observed. Here, we report time-resolved whole-genome transcriptome profiles of multiple, naturally occurring oceanic bacterial populations sampled in situ over 3 days. As anticipated, the cyanobacterial transcriptome exhibited pronounced diel periodicity. Unexpectedly, several different heterotrophic bacterioplankton groups also displayed diel cycling in many of their gene transcripts. Furthermore, diel oscillations in different heterotrophic bacterial groups suggested population-specific timing of peak transcript expression in a variety of metabolic gene suites. These staggered multispecies waves of diel gene transcription may influence both the tempo and the mode of matter and energy transformation in the sea.
A Highly Efficient Chemoenzymatic Approach toward Glycoprotein Synthesis (2006)

[reaction: see text] A highly efficient endoglycosidase-catalyzed synthesis of homogeneous glycoproteins is described. By using ribonuclease B as a model system, it was demonstrated that Endo-A could efficiently attach a preassembled oligosaccharide to a GlcNAc-containing protein in a regio- and stereospecific manner, when the corresponding sugar oxazoline was used as the donor substrate. The method allows the synthesis of both natural and tailor-made N-linked glycoproteins in excellent yield.
Role of CD44 in tumour progression and strategies for targeting (2012)

CD44 or hyaluronan receptor is a transmembrane receptor associated with aggressive tumour growth, proliferation, and metastasis. In normal physiology, this receptor has a crucial role in cell adhesion, inflammation, and repair processes. However, many tumour cells over-express this receptor and abuse it to become progressive and perpetual units. The article comments from common functioning of the CD44 receptor, to its diabolic multi-dimensional effects in promotion of malignant cells. It also illuminates the relations of CD44 endorsed processes with other biomolecular events in cancer progression. In an end, the review focuses comprehensively at ongoing researches to exploit the CD44 over-expression as a probable target in treatment, management, and diagnosis of malignancy.
MMP-7 and SGCE as distinctive molecular factors in sporadic colorectal cancers from the mutator phenotype pathway (2010)

Colorectal cancers (CRCs) from the suppressor and the mutator carcinogenic pathways display distinctive pathological and clinical features that remain not completely understood. In this context, the aim of this work was to study the differential expression of metalloproteinases and adhesion molecules related to cancer invasiveness in both groups of tumours. We analyzed 84 tissue specimens, 42 primary sporadic CRCs obtained from patients who underwent radical surgery, and its corresponding control tissues. According to microsatellite instability, 31 cancers showed low or null microsatellite instability (MSI-L/MSS) and 11 tumours displayed high microsatellite instability (MSI-H). Expression assays were established using the Oligo GEArray(R) human extracellular matrix and adhesion molecules microarray containing 114 genes. Real-time quantitative PCR (RT-qPCR) confirmed expression data from arrays, using TaqMan probes. Results from oligoarray expression analyses indicated that ITGA3, ITGA9, ITGB4, ITGB7 and MMP15 had significantly higher expression levels in MSI-H tumours versus MSS/MSI-L cancers, whereas COL12A1, CSPG2, FN1, MMP-7 and SGCE were down-regulated in tumours with high microsatellite instability when compared to the stable group. After RT-qPCR validation, two of these genes, MMP-7 and SGCE, were confirmed to have statistical differences between the two groups of tumours studied. In both cases, MSI-H tumours displayed significant lower expression levels than MSI-L/MSS tumours. In conclusion, these two distinctive molecular markers could be related to a diminished invasion in colorectal tumours from the mutator pathway, this may contribute to the understanding of the better patient prognosis conferred by this type of tumours.
Results of a Triple Blind Clinical Study of Myoblast Transplantations without Immunosuppressive Treatment in Young Boys with Duchenne Muscular Dystrophy (1993)

The effects of myoblast transplantations without an immunosuppressive treatment on muscle strength, and the formation of dystrophin-positive fibers was studied in five young boys with Duchenne muscular dystrophy (DMD) using a triple blind design. Injections of myoblasts were made into one biceps brachii (BB), and the opposite BB, used as a control, was sham-injected; the experimenters and the patient were blind to the myoblast-injected side. At the same time, myoblasts were also injected in the left tibialis anterior (TA) of these patients. The strength developed during maximal static contractions of the elbow flexor and extensor muscles was measured with a Kin-Com dynamometer. No increase in static elbow flexion torque was measured at any time from 2 mo up to 18 mo after the transplantation. One month after the transplantation, the percentage of dystrophin-positive fibers in the myoblast-injected TA ranged from 0 to 36%, while it ranged from 0 to 4% on the control side. The expression of dystrophin in these fibers, however, was generally low, and most likely less than 10% of the normal level. In the biceps brachii of both sides 6 mo after the transplantation, less than 1.5% of dystrophin-positive fibers were detected. The injections also triggered a humoral immune response of the host. Antibodies were capable of fixing the complement, and of lysing the newly formed myotubes. One of the antigens recognized by this immune response is possibly dystrophin. These results strongly suggest that myoblast transplantations, as well as gene therapy for DMD, cannot be done without immunosuppression.
Amyloids and Are Generated Intracellularly in Cultured Human Neurons and Their Secretion Increases with Maturation (1996)

Previous studies have demonstrated the presence of amyloid beta (Abeta) in neurons (NT2N) derived from a human embryonal carcinoma cell line (NT2) by steady state metabolic radiolabeling and immunoprecipitation. We show here that Abeta is present intracellularly since trypsin digestion of intact NT2N cells at 4 degrees C did not eliminate the Abeta recovered in cell lysates. To determine whether both Abeta40 and Abeta42 are produced intracellularly, quantitative sandwich enzyme-linked immunosorbent assay (ELISA) was performed using COOH-terminal end-specific anti-Abeta monoclonal antibodies. Sandwich ELISA detected intracellular Abeta40 and A++beta42 in NT2N cell lysates at a ratio of 3:1, whereas secreted Abeta40 and Abeta42 were recovered in medium conditioned by NT2N cells at a ratio of approximately 20:1. Metabolic steady state and pulse-chase labeling studies demonstrated a 2-h delay in the detection of cell-associated Abeta40/Abeta42 in the medium, suggesting that Abeta is generated at a slow rate intracellularly prior to its secretion. Finally, as NT2N cells mature over time in culture, the secretion of Abeta40 and Abeta42 increases more than 5-fold over 7 weeks. This increase in the secretion of Abeta40/Abeta42 in NT2N cells as a function of time may recapitulate a similar phenomenon in the aging brain.
Microglial response to amyloid plaques in APPsw transgenic mice. (1998)

Microglial activation is central to the inflammatory response in Alzheimer's Disease (AD). A recently described mouse line, Tg(HuAPP695.K670N/M671L)2576, expressing human amyloid precursor protein with a familial AD gene mutation, age-related amyloid deposits, and memory deficits, was found to develop a significant microglial response using Griffonia simplicifolia lectin or phosphotyrosine probe to identify microglia Both Griffonia simplicifolia lectin and phosphotyrosine staining showed increased numbers of intensely labeled, often enlarged microglia clustered in and around plaques, consistent with microglial activation related to beta-amyloid formation. Using quantitative image analysis of coronal phosphotyrosine-immunostained sections, transgene-positive 10- to 16-month-old, hemizygous, hybrid Tg2576 (APPsw) animals showed significantly increased microglial density and size in plaque-forming areas of hippocampus and frontal, entorhinal, and occipital cortex. Quantitative analysis of microglia as a function of distance from the center of plaques (double labeled for A beta peptide and microglia) revealed highly significant, two- to fivefold elevations in microglial number and area within plaques compared with neighboring regions. Tg2576 beta-amyloid-plaque-forming mice should be a useful system for assessing the consequences of the microglial-mediated inflammatory response to beta-amyloid and developing anti-inflammatory therapeutic strategies for Alzheimer's disease. These results provide the first quantitative link between beta-amyloid plaque formation and microglial activation in an animal model with neuritic plaques and memory deficits.
Single Ion-Channel Recordings Using Glass Nanopore Membranes (2007)

Protein ion-channel recordings using a glass nanopore (GNP) membrane as the support structure for lipid bilayer membranes are presented. The GNP membrane is composed of a single conical-shaped nanopore embedded in a approximately 50 microm-thick glass membrane chemically modified with a 3-cyanopropyldimethylchlorosilane monolayer to produce a surface of intermediate hydrophobicity. This surface modification results in lipid monolayer formation on the glass surface and a lipid bilayer suspended across the small orifice (100-400 nm-radius) of the GNP membrane, while allowing aqueous solutions to fully wet the glass nanopore. The GNP membrane/bilayer structures, which exhibit ohmic seal resistances of approximately 70 GOmega and electrical breakdown voltages of approximately 0.8 V, are exceptionally stable to mechanical disturbances and have lifetimes of at least 2 weeks. These favorable characteristics result from the very small area of bilayer (10(-10)-10(-8) cm(2)) that is suspended across the GNP membrane orifice. Fluorescence microscopy and vibrational sum frequency spectroscopy demonstrate that a lipid monolayer forms on the 3-cyanopropyl-dimethylchlorosilane modified glass surface with the lipid tails oriented toward the glass. The GNP membrane/bilayer structure is well suited for single ion-channel recordings. Reproducible insertion of the protein ion channel, wild-type alpha-hemolysin (WTalphaHL), and stochastic detection of a small molecule, heptakis(6-O-sulfo)-beta-cyclodextrin, are demonstrated. In addition, the insertion and removal of WTalphaHL channels are reproducibly controlled by applying small pressures (-100 to 350 mmHg) across the lipid bilayer. The electrical and mechanical stability of the bilayer, the ease of which bilayer formation is achieved, and the ability to control ion-channel insertion, coupled with the small bilayer capacitance of the GNP membrane-based system, provide a new and nearly optimal system for single ion-channel recordings.
Vascular endothelial growth factor/KDR activated microvessel density versus CD31 standard microvessel density in non-small cell lung cancer. (2000)

Vascular endothelial growth factor (VEGF) is an important angiogenic factor, linked to poor outcome in human malignancies including non-small cell lung carcinoma (NSCLC). We used the 11B5 monoclonal antibody recognizing the VEGF/KDR complex (R. A. Brekken et al., Cancer Res., 58: 1952-1959, 1998) to assess the VEGF expression in cancer cells and the VEGF/KDR activated microvessel density (aMVD) in early operable NSCLC. The JC70 anti-CD31 monoclonal antibody was used to assess the standard MVD (sMVD). The aMVD was significantly higher in the invading front of the tumors and in the normal lung adjacent to the tumors as compared with normal lung distant to the tumor or to inner tumor areas (P < 0.0002). The sMVD was higher in the normal lung and decreased from the invading front to inner tumor areas (P < 0.0001). However, the vascular activation (aMVD:sMVD) was 4-6 times higher in the tumor areas as compared with lung from normal individuals (36-58% versus 9%; P < 0.0001). Fibroblast 11B5 reactivity, noted in 25% of cases, correlated with high aMVD and sMVD in the inner tumor areas. Multivariate analysis showed that aMVD was the most potent and independent prognostic factor (P = 0.001; t-ratio, 3.28). It is concluded that intense VEGF/KDR angiogenic pathway activation is a tumor-specific feature in more than 50% of NSCLC cases and is associated with poor postoperative outcome. Clinical trials involving targeting of the VEGF/KDR-positive vasculature with specific antibodies, such as 11B5, are, therefore, encouraged.
Ethylene stimulates the accumulation of ripening‐related mRNAs in tomatoes (1987)

Abstract Seven cDNA clones for ripening‐related mRNAs were used as hybridization probes to study the regulation of gene expression during tomato ( Lycopersicon esculentum Mill) ripening. The mRNAs corresponding to each clone were detected by Northern blotting and the sizes of the transcripts compared with the molecular weights of polypeptides identified previously by hybrid‐release translation. Dot hybridization to poly(A)+ mRNA from leaves, roots, unripe and ripe tomatoes established that five of the clones encoded mRNAs that were ripening specific and two encoded mRNAs also expressed in other organs. Appearance of these ripening‐specific mRNAs was correlated with ethylene production as ripening commenced and occurred before lycopene synthesis began. Thereafter, the mRNAs increased to maximum levels at the orange stage and then declined slowly as fruit turned red. When mature green fruit were picked before any increase in ethylene synthesis occurred and placed in air plus 10 cm 3 m −3 ethylene, substantial changes in translatable mRNA were noted within 30 h. Five mRNAs that increased in amount directed the synthesis in vitro of polypeptides similar in size to those encoded by the five ripening‐specific clones. Several different patterns of mRNA accumulation were observed, with increases in concentration of the order of 300‐fold.
Oxidized Lipids Block Antigen Cross-Presentation by Dendritic Cells in Cancer (2014)

Cross-presentation is one of the main features of dendritic cells (DCs), which is critically important for the development of spontaneous and therapy-inducible antitumor immune responses. Patients, at early stages of cancer, have normal presence of DCs. However, the difficulties in the development of antitumor responses in patients with low tumor burden raised the question of the mechanisms of DC dysfunction. In this study, we found that, in differentiated DCs, tumor-derived factors blocked the cross-presentation of exogenous Ags without inhibiting the Ag presentation of endogenous protein or peptides. This effect was caused by intracellular accumulation of different types of oxidized neutral lipids: triglycerides, cholesterol esters, and fatty acids. In contrast, the accumulation of nonoxidized lipids did not affect cross-presentation. Oxidized lipids blocked cross-presentation by reducing the expression of peptide-MHC class I complexes on the cell surface. Thus, this study suggests the novel role of oxidized lipids in the regulation of cross-presentation.