gebhart/patrepeval huggingface dataset:
Targeting ErbB2 and ErbB3 with a bispecific single-chain Fv enhances targeting selectivity and induces a therapeutic effect in vitro (2008)

Inappropriate signalling through the EGFR and ErbB2/HER2 members of the epidermal growth factor family of receptor tyrosine kinases is well recognised as being causally linked to a variety of cancers. Consequently, monoclonal antibodies specific for these receptors have become increasingly important components of effective treatment strategies for cancer. Increasing evidence suggests that ErbB3 plays a critical role in cancer progression and resistance to therapy. We hypothesised that co-targeting the preferred ErbB2/ErbB3 heterodimer with a bispecific single-chain Fv (bs-scFv) antibody would promote increased targeting selectivity over antibodies specific for a single tumour-associated antigen (TAA). In addition, we hypothesised that targeting this important heterodimer could induce a therapeutic effect. Here, we describe the construction and evaluation of the A5-linker-ML3.9 bs-scFv (ALM), an anti-ErbB3/ErbB2 bs-scFv. The A5-linker-ML3.9 bs-scFv exhibits selective targeting of tumour cells in vitro and in vivo that co-express the two target antigens over tumour cells that express only one target antigen or normal cells that express low levels of both antigens. The A5-linker-ML3.9 bs-scFv also exhibits significantly greater in vivo targeting of ErbB2'+'/ErbB3'+' tumours than derivative molecules that contain only one functional arm targeting ErbB2 or ErbB3. Binding of ALM to ErbB2'+'/ErbB3'+' cells mediates inhibition of tumour cell growth in vitro by effectively targeting the therapeutic anti-ErbB3 A5 scFv. This suggests both that ALM could provide the basis for an effective therapeutic agent and that engineered antibodies selected to co-target critical functional pairs of TAAs can enhance the targeting specificity and efficacy of antibody-based cancer therapeutics.
Genotypic and phenotypic analyses of a Pseudomonas aeruginosa chronic bronchiectasis isolate reveal differences from cystic fibrosis and laboratory strains (2015)

This work provides insights into the potential differential adaptation of this bacterium to the lung of patients with bronchiectasis compared to other clinical settings such as cystic fibrosis, findings that should aid the development of disease-appropriate treatment strategies for P. aeruginosa infections.
Expression and Clinical Significance of Androgen Receptor in Triple-Negative Breast Cancer (2017)

AR expression may be useful as a subclassification marker for prognosis in TNBC.
Theory of Spread-Spectrum Communications - A Tutorial (1982)

Spread-spectrum communications, with its inherent interference attenuation capability, has over the years become an increasingly popular technique for use in many different systems. Applications range from antijam systems, to code division multiple access systems, to systems designed to combat multipath. It is the intention of this paper to provide a tutorial treatment of the theory of spread-spectrum communications, including a discussion on the applications referred to above, on the properties of common spreading sequences, and on techniques that can be used for acquisition and tracking.
Human Genome Sequencing Using Unchained Base Reads on Self-Assembling DNA Nanoarrays (2009)

Genome sequencing of large numbers of individuals promises to advance the understanding, treatment, and prevention of human diseases, among other applications. We describe a genome sequencing platform that achieves efficient imaging and low reagent consumption with combinatorial probe anchor ligation chemistry to independently assay each base from patterned nanoarrays of self-assembling DNA nanoballs. We sequenced three human genomes with this platform, generating an average of 45- to 87-fold coverage per genome and identifying 3.2 to 4.5 million sequence variants per genome. Validation of one genome data set demonstrates a sequence accuracy of about 1 false variant per 100 kilobases. The high accuracy, affordable cost of $4400 for sequencing consumables, and scalability of this platform enable complete human genome sequencing for the detection of rare variants in large-scale genetic studies.
Calcium Phosphate Nanoparticle Adjuvant (2000)

Vaccination to protect against human infectious diseases may be enhanced by using adjuvants that can selectively stimulate immunoregulatory responses. In a murine model, a novel nanoparticulate adjuvant composed of calcium phosphate (CAP) was compared with the commonly used aluminum (alum) adjuvants for its ability to induce immunity to herpes simplex virus type 2 (HSV-2) and Epstein-Barr virus (EBV) infections. Results indicated that CAP was more potent as an adjuvant than alum, elicited little or no inflammation at the site of administration, induced high titers of immunoglobulin G2a (IgG2a) antibody and neutralizing antibody, and facilitated a high percentage of protection against HSV-2 infection. Additional benefits of CAP include (i) an insignificant IgE response, which is an important advantage over injection of alum compounds, and (ii) the fact that CAP is a natural constituent of the human body. Thus, CAP is very well tolerated and absorbed. These studies were performed with animal models. By virtue of the potency of this CAP adjuvant and the relative absence of side effects, we believe that this new CAP formulation has great potential for use as an adjuvant in humans.
Chronic hepatitis B virus infection in Polynesians. (1994)

Genetic differences between Polynesians and Europeans may contribute to the many differences in disease frequency that occur between these races. This thesis describes studies that were designed to determine if genetic influences contribute to the high prevalence of chronic hepatitis B virus (HBV) infection in Polynesians. Alleles suitable for gene flow measurements were identified and used to find associations between European genes and indices of chronic HBV infection in Polynesians. An ecologic study found a negative association between European genes and the prevalence of chronic HBV infection in five Polynesian ethnic groups (p<0.05). In a case control study, there was a positive correlation (r=0.90, p=0.04) between the percent of European genes in a Polynesian ethnic group and the difference in the percent of European genes between the HBV carriers and the anti-HBs positive controls in that ethnic group. Thus, the possibility that genetic factors are a major cause of the high prevalence of chronic HBV infection in Polynesians cannot be excluded. A twin study or candidate gene studies will be necessary to take this work further. We attempted to identify candidate genes in the Tcr β chain variable region (V β)locus that might contain polymorphisms that influence the human in vivo immune response to the HBV. Vβ7.4 was associated with the immune response to a vaccine containing recombinant HBsAg in two separate studies (p<0.0001 and p=0.05). The frequency of.Vβ7.4 was low in the cord blood of neonates born to HBsAg positive mothers (p=0.001). The frequency of Vβ5.1 was high in the cord blood of neonates of HBeAg positive mothers (p<0.001). Thus the Vβ7.4 and Vβ5.1 genes may be preferentially used in the human immune response to the HBV and may be an appropriate place to seek polymorphisms that influence the immune response to the HBV and susceptibility to a chronic HBV infection.
Iron deficiency: new insights into diagnosis and treatment (2015)

Iron deficiency and iron deficiency anemia are common conditions worldwide affecting especially children and young women. In developing countries, iron deficiency is caused by poor iron intake and/or parasitic infection, whereas vegetarian dietary choices, poor iron absorption, and chronic blood loss are common causes in high-income countries. Erythropoiesis stimulating agents can result in functional iron deficiency for erythropoiesis even when stores are iron-replete. Diagnosis of iron deficiency is straightforward, except when it occurs in the context of inflammatory disorders. Oral iron salts correct absolute iron deficiency in most patients, because low hepcidin levels facilitate iron absorption. Unfortunately frequent side effects limit oral iron efficacy. Intravenous iron is increasingly utilized, because currently available preparations allow rapid normalization of total body iron even with a single infusion and are effective also in functional iron deficiency and in iron deficiency associated with inflammatory disorders. The evidence is accumulating that these preparations are safe and effective. However, long-term safety issues of high doses of iron need to be further explored.
Effects of Endocardial Microwave Energy Ablation\n (2005)

Until recently the treatment of atrial fibrillation (AF) consisted primarily of palliation, mostly in the form of pharmacological intervention. However because of recent advances in nonpharmacologic therapies, the current expectation of patients and referring physicians is that AF will be cured, rather than palliated. In recent years there has been a rapid expansion in the availability and variety of energy sources and devices for ablation. One of these energies, microwave, has been applied clinically only in the last few years, and may be a promising technique that is potentially capable of treating a wide range of ventricular and supraventricular arrhythmias. The purpose of this study was to review microwave energy ablation in surgical treatment of AF with special interest in histology and ultrastructure of lesions produced by this endocardial ablation procedure.\n
Direct functionalization of 4,5‐dichloropyridazin‐6‐one (1999)

Abstract Direct functionalization of 4,5‐dichloropyridazin‐6‐one with some nucleophiles in seven solvents gave regioselectively 5‐halo‐4‐substituted‐pyridazin‐6‐ones as main product. Reaction of 4,5‐dichloropyridazin‐6‐one with 2‐mercaptopyrimidine (2 equivalents) also afforded 4,5‐di(pyrimidin‐2‐ylsulfanyl)pyridazin‐6‐one as the main product.
WS009 A and B, new endothelin receptor antagonists isolated from Streptomyces sp. No. 89009. II. Biological characterization and pharmacological characterization of WS009 A and B. (1992)

WS009 A and B, produced by Streptomyces sp. No. 89009, were found to be competitive and specific antagonists against endothelin (ET)-1 receptors in in vitro studies and also active in in vivo studies. Furthermore, WS009 A and B were specific antagonists for vascular ET-1 receptors (ETA receptors) and significantly prevented the accumulation of intracellular inositol 1,4,5-triphosphate (IP3) in endothelin treated rat aorta tissues.
Enhancement of Gene Therapy Specificity for Diffuse Colon Carcinoma Liver Metastases with Recombinant Herpes Simplex Virus (1996)

The hrR3 HSV vector effectively destroys HT29 human colon carcinoma cells at very low multiplicities of infection. Differential expression of ribonucleotide reductase between liver metastases and normal liver allows hrR3 to selectively replicate in tumor cells with minimal replication in surrounding normal liver. Further investigation of HSV-based vectors as oncolytic agents for liver metastases is warranted.
Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: Design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial (2014)

This is the first and only study of a new class of LDL-C-lowering agents in patients selected with a rigorously documented intolerance to statins, using a placebo run-in and statin control arm.
Potential Bile Acid Metabolites. 25. Synthesis and Chemical Properties of Stereoisomeric 3.ALPHA.,7.ALPHA.,16- and 3.ALPHA.,7.ALPHA.,15-Trihydroxy-5.BETA.-cholan-24-oic Acids. (2002)

Epimeric 3alpha,7alpha,16- and 3alpha,7alpha,15-trihydroxy-5beta-cholan-24-oic acids and some related compounds were synthesized from chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), respectively. The key reaction involved one-step remote oxyfunctionalization of unactivated methine carbons at C-17 of CDCA and at C-14 of UDCA as their methyl ester-peracetate derivatives with dimethyldioxirane (DMDO). After dehydration of the resulting 17alpha- and 14alpha-hydroxy derivatives with POCl(3) or conc. H(2)SO(4), the respective Delta(16)- and Delta(14)-unsaturated products were subjected to hydration via hydroboration followed by oxidation to yield the 3,7,16- and 3,7,15-triketones, respectively. Stereoselective reduction of the respective triketones with tert-butylamine-borane complex afforded the epimeric 3alpha,7alpha,16- or 3alpha,7alpha,15-trihydroxy derivatives exclusively. A facile formation of the corresponding epsilon-lactones between the side chain carboxyl group at C-24 and the 16alpha- (or 16beta-) hydroxyl group in bile acids is also clarified.
Clone- and Gene-Specific Aberrations of Parental Imprinting in Human Induced Pluripotent Stem Cells (2009)

Genomic imprinting is an epigenetic phenomenon whereby genes are expressed in a monoallelic manner, which is inherited either maternally or paternally. Expression of imprinted genes has been examined in human embryonic stem (ES) cells, and the cells show a substantial degree of genomic imprinting stability. Recently, human somatic cells were reprogrammed to a pluripotent state using various defined factors. These induced pluripotent stem (iPS) cells are thought to have a great potential for studying genetic diseases and to be a source of patient-specific stem cells. Thus, studying the expression of imprinted genes in these cells is important. We examined the allelic expression of various imprinted genes in several iPS cell lines and found polymorphisms in four genes. After analyzing parent-specific expression of these genes, we observed overall normal monoallelic expression in the iPS cell lines. However, we found biallelic expression of the H19 gene in one iPS cell line and biallelic expression of the KCNQ10T1 gene in another iPS cell line. We further analyzed the DNA methylation levels of the promoter region of the H19 gene and found that the cell line that showed biallelic expression had undergone extensive DNA demethylation. Additionally we studied the imprinting gene expression pattern of multiple human iPS cell lines via DNA microarray analyses and divided the pattern of expression into three groups: (a) genes that showed significantly stable levels of expression in iPS cells, (b) genes that showed a substantial degree of variability in expression in both human ES and iPS cells, and (c) genes that showed aberrant expression levels in some human iPS cell lines, as compared with human ES cells. In general, iPS cells have a rather stable expression of their imprinted genes. However, we found a significant number of cell lines with abnormal expression of imprinted genes, and thus we believe that imprinted genes should be examined for each cell line if it is to be used for studying genetic diseases or for the purpose of regenerative medicine.
Chemical Strategies for Activity‐Based Proteomics (2003)

The assignment of molecular and cellular functions to the numerous protein products encoded by prokaryotic and eukaryotic genomes presents a major challenge for the field of proteomics. To address this problem, chemical approaches have been introduced that utilize small-molecule probes to profile dynamics in enzyme activity in complex proteomes. These strategies for activity-based protein profiling enable both the discovery and functional analysis of enzymes associated with human disease.
Gene expression profiles from needle biopsies provide useful signatures of non-small cell lung carcinomas. (2007)

Gene expression profiles from DNA microarrays can provide molecular signatures that improve tumor classification, prognosis, and treatment options. While much of this work has focused on isolation of RNA from the resected tumor, fewer studies have utilized RNA from fine needle aspirates (FNA). In this pilot study we examined whether the gene signatures obtained from FNA samples would correlate with signatures taken from the resected tumor. Based on NSCLC gene expression profiles obtained from eleven sets of FNA and tumor samples we obtained a high concordance of FNA profiles matching their matched tumor sample. These results suggest that FNA samples may provide informative gene expression signatures regarding the potential aggressiveness of non-small-cell lung carcinomas.
Polyisobutylene‐based polyurethanes. III. Polyurethanes containing PIB/PTMO soft co‐segments (2009)

Abstract The synthesis, characterization, and structure–property behavior of polyurethanes containing polyisobutylene (PIB)/poly(tetramethylene oxide) (PTMO) soft co‐segments and bis(4‐isocyanatocyclohexyl)methane (HMDI)/hexanediol (HDO) hard segments is presented. The mechanical (stress/strain, hardness, and hysteresis) properties of these novel polyurethanes were investigated over a broad composition range. PIB‐based polyurethanes with HMDI/HDO hard segments showed better mechanical properties than earlier polyurethanes containing highly crystalline hard segments. The addition of moderate amounts (20% by weight) of PTMO significantly increased both tensile strengths and elongation. In the presence of larger amounts of PIB, these polyurethanes are expected to possess oxidative/hydrolytic/enzymatic stabilities superior to commercially available polyurethanes. These polyurethanes are softer and exhibit hysteresis superior to or comparable with conventional polyurethanes. According to initial thermal studies, these materials show good melt processibility. Overall, the mechanical properties of PIB based hybrid polyurethanes are similar to commercially important polyurethane type biomaterials. Our results show that the incorporation of PTMO segments to PIB‐based polyurethanes significantly improves elastomeric properties. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 5278–5290, 2009
The PEP—pyruvate—oxaloacetate node as the switch point for carbon flux distribution in bacteria: We dedicate this paper to Rudolf K. Thauer, Director of the Max-Planck-Institute for Terrestrial Microbiology in Marburg, Germany, on the occasion of his 65th birthday (2004)

In many organisms, metabolite interconversion at the phosphoenolpyruvate (PEP)-pyruvate-oxaloacetate node involves a structurally entangled set of reactions that interconnects the major pathways of carbon metabolism and thus, is responsible for the distribution of the carbon flux among catabolism, anabolism and energy supply of the cell. While sugar catabolism proceeds mainly via oxidative or non-oxidative decarboxylation of pyruvate to acetyl-CoA, anaplerosis and the initial steps of gluconeogenesis are accomplished by C3- (PEP- and/or pyruvate-) carboxylation and C4- (oxaloacetate- and/or malate-) decarboxylation, respectively. In contrast to the relatively uniform central metabolic pathways in bacteria, the set of enzymes at the PEP-pyruvate-oxaloacetate node represents a surprising diversity of reactions. Variable combinations are used in different bacteria and the question of the significance of all these reactions for growth and for biotechnological fermentation processes arises. This review summarizes what is known about the enzymes and the metabolic fluxes at the PEP-pyruvate-oxaloacetate node in bacteria, with a particular focus on the C3-carboxylation and C4-decarboxylation reactions in Escherichia coli, Bacillus subtilis and Corynebacterium glutamicum. We discuss the activities of the enzymes, their regulation and their specific contribution to growth under a given condition or to biotechnological metabolite production. The present knowledge unequivocally reveals the PEP-pyruvate-oxaloacetate nodes of bacteria to be a fascinating target of metabolic engineering in order to achieve optimized metabolite production.
Effective interference: a novel approach for interference modelling and traffic analysis in CDMA cellular networks (2002)

This paper presents an analysis of the reverse link capacity of cellular mobile communication networks operating with direct sequence code division multiple access. The emphasis is on dealing with the variability in user locations and on allowing different numbers of users in each cell. Firstly we calculate the distribution function of the interference at a cell site from a single mobile whose position is a random vector in another cell of the network. Using ideas closely related to the effective bandwidth concept from the analysis of call admission control in ATM networks, a method of handling the sum of the interference from arbitrary numbers of users in each cell is presented. This leads to a set of linear constraints that bounds the capacity region of the network and to the assignment of an effective interference to users. Importantly, the method is readily incorporated into a traffic model which allows the stochastic nature of the call arrival process to be analysed and the Erlang capacity of the network to be calculated.
Isolation of Muscle Stem Cells by Fluorescence Activated Cell Sorting Cytometry (2011)

Satellite cells are a heterogeneous population of muscle progenitors with stem cell properties responsible for the regeneration of adult skeletal muscle. Increasing interest in the therapeutic potential of satellite cells has challenged researchers with the need to purify a homogenous population of muscle progenitors. Here we provide a detailed protocol for the isolation of a pure population of satellite cells using fluorescence activated cell sorting. We give specific guidelines to ameliorate the reproducibility of the satellite cell isolation protocol with the goal to standardize procedures across labs. This protocol identifies satellite cells within adult skeletal muscle as an enriched population of Integrin α7(+)/CD34(+) double positive cells and CD45, CD31, CD11b, and Sca1 negative (Lin(-)) cells (Integrin α7(+)/CD34(+)/Lin(-)). Functional assay shows that Integrin α7(+)/CD34(+)/Lin(-) satellite cells possess high myogenic potential and ability to regenerate muscle depleted satellite cells upon transplantation.
Cell autonomous expression of IgD is not essential for the maturation of conventional B cells (1991)

To analyse the function of IgD in vivo, we generated a 'loss of function' mouse model utilizing gene targeting technology. By homologous recombination in a (C57BL/6 x CBA)F1 mouse embryonic stem cell (ES) line one allele of the delta heavy chain gene was rendered non-functional. In chimeric mice obtained after injection of the targeted ES cells into blastocysts derived from severe combined immunodeficient mice we analysed ES cell derived B lymphocytes expressing the targeted or the wild-type allele by using allotype specific reagents. We show that B cells expressing the targeted allele appear in the periphery as IgM+ D- cells at normal frequency. They express the CD23 marker and respond to a T cell dependent antigen. Thus, cell autonomous expression of IgD is neither essential for B cell maturation into an antigen responsive state nor for antigen dependent triggering of the cells into an immune response.
Erythropoietin Levels in Heterozygous Beta-Thalassemia (1984)

In the present work the capacity of serum of beta-thalassemic heterozygous and normal subjects to stimulate 59Fe uptake into heme in guinea pig bone marrow cultures is analyzed. The results show that labelled iron uptake is higher in cultures with thalassemic serum than in cultures with normal serum. No correlation between labelled iron uptake and Hb level or sex has been found in either group.