gebhart/patrepeval huggingface dataset:
Characterization of epithelial phenotypes in mortal and immortal human breast cells (1992)

Abstract We have previously described the mortal human breast epithelial culture MCF‐10M, that was derived from fibrocystic breast tissue, was cultivated in medium with low calcium content for over 2 years, and spontaneously gave rise to the immortal MCF‐10 cell line. The emergence of immortalized cells, characterized by growth in conventional calcium levels, from mortal cells has proven to be a reproducible event. Here we report the establishment of a second immortal line from MCF‐10M, designated MCF‐10‐2, and establishment of the MCF‐12 immortal line after long‐term cultivation of MCF‐12M mortal cells from reduction mammoplasty tissue. DNA fingerprinting demonstrated the independent, human origin and lineage of the MCF‐10‐2 and MCF‐12 cell lines. Both lines require cortisol and EGF for maximal growth. The expression in these cultures of in vivo breast epithelial phenotypes was analyzed using 2‐dimensional gel Western blots and immunoper‐ oxidase staining with antibodies to cytokeratins and polymorphic epithelial mucin. MCF‐10M and MCF‐12M retain the cytokeratin profile of the luminal cell (7, 8, 18, 19), and also express cytokeratin 14, found predominantly in basal cells. The immortal lines express a similar profile, except that cytokeratin 19, a component of the fully differentiated luminal cell, is not expressed in the more uniform population seen in MCF‐10 and MCF‐12, but is retained in the morphologically mixed, less‐ selected population of MCF‐10‐2. Epitopes on the polymorphic epithelial mucin, recognized by antibodies HMFG 1, HMFG 2 and SM‐3, were detected in the mortal cultures and in the immortal lines, indicating the occurrence of both normal and abnormal mucin processing. MCF‐10, MCF‐10‐2 and MCF‐12 cells do not form tumors in nude mice, but appear to organize as duct‐like structures before regressing in the 5th week post injection.
Controlled Synthesis of Hyperbranched Polyglycerols by Ring-Opening Multibranching Polymerization (1999)

Glycidol represents a latent cyclic AB2-type monomer that can be polymerized in a ring-opening multibranching polymerization (ROMBP). Hyperbranched aliphatic polyethers with controlled molecular weights and narrow molecular weight distribution have been prepared via anionic polymerization of glycidol with rapid cation-exchange equilibrium. 1,1,1-Tris(hydroxymethyl)propane (TMP) was partially deprotonated (10%) and used as initiator for the anionic polymerization carried out under slow addition conditions to minimize polymerization without initiator as well as cyclization. 13C NMR spectra were employed to assess the degree of branching (DB), which was in the range 0.53−0.59. 13C NMR, MALDI-TOF mass spectrometry, vapor pressure osmometry (VPO), and GPC were used to characterize molecular weights and polydispersities of the polyols formed, showing good agreement. n for the polymers prepared was in the range 15−83 (M̄n = 1250−6500), and M̄w/M̄n obtained was 1.13−1.47, being exceptionally low for hyperbranched polymers. MALDI-TOF spectra evidenced complete attachment of the hyperbranched structures to the TMP initiator and the absence of macrocyclics as well as hyperbranched macromolecules without initiator, due to the slow addition. The hyperbranched polyethers prepared showed Tg's between −20 and − 26 °C.
Venous ulcers: pathophysiology and treatment options. (2005)

Venous ulcers affect approximately 1% of the world's population, increasing healthcare expenditures and decreasing quality of life. Several hypotheses may help explain their origin. Incompetent veins or valves or impaired muscle function may lead to abnormal calf muscle pump function that can elevate ambulatory venous pressure (venous hypertension). This hypertension subsequently results in local venous dilatation and pooling, concomitantly trapping leukocytes that may release proteolytic enzymes that destroy tissues. Venous pooling also induces interendothelial pore widening and deposition of fibrin and other macromolecules that "trap" growth factors within them, rendering them unavailable for wound repair. Compression therapy, the mainstay treatment, reduces edema, reverses venous hypertension, and improves calf muscle pump function. Several treatment options can be employed as adjuvants to compression--eg, systemic therapy with pentoxifylline or aspirin, autologous grafts, tissue-engineered skin, growth factor therapy, and/or vein surgery. The epidemiology, pathophysiology, diagnosis, and management options regarding venous ulcers are reviewed.
Systemic immunization with pneumococcal polysaccharide vaccine induces a predominant IgA2 response of peripheral blood lymphocytes and increases of both serum and secretory anti-pneumococcal antibodies. (1988)

Ig class-, and IgA and IgG subclass-specific immune responses to a 23 valent pneumococcal polysaccharide vaccine were studied at a single-cell level in the peripheral blood of systemically immunized adults. With a solid phase enzyme-linked immunospot (ELISPOT) assay, PBMC from immunized individuals were assayed for spontaneous Ag-specific antibody (Ab) production before, and on days 7, 14, and 28 after vaccination. On the day of immunization, no spontaneous Ag-specific Ab-secreting cells could be detected. On day 7 after vaccination, a high frequency of cells secreting Ab specific for pneumococcal polysaccharides (PPS) was observed. The IgA class comprised 79% (geometric mean) of the Ag-specific Ab-secreting cells, whereas IgG- and IgM-secreting cells accounted for 12% and 9%, respectively. The majority of Ag-specific IgA-secreting cells produced Ab of the IgA2 isotype. Serum, saliva, and tears collected before and on days 7, 14, and 28 after vaccination were assayed for specific Ab to the vaccine (anti-PPS Ab) by an ELISA. Serum IgA anti-PPS Ab showed the highest increase after vaccination with a 19-fold increase (geometric mean) which peaked on day 14. However, the ratio of Ag-specific polymeric vs monomeric IgA did not change after immunization. Serum IgG and IgM anti-PPS Ab displayed mean increases of 5.5-fold and 5.6-fold, respectively, on day 14. The most pronounced increase of salivary anti-PPS Ab was observed in the IgG class (4.5-fold on day 28) followed by IgM (4-fold on day 28), IgA (2.0-fold on day 14), IgA1 (2.4-fold on day 14) and IgA2 (2.0-fold on day 14). The levels of total IgA, IgG, and IgM in saliva did not change significantly throughout the course of immunization. IgG and IgM anti-PPS Ab levels in tears increased less than in saliva, whereas IgA behaved similarly as in saliva. There were no significant differences in the Ag-specific increase rates between the IgA, IgG, and IgM isotypes in tears.
Lamellar Lα Mesophases Doped with Inorganic Nanoparticles (2014)

The development of nanostructured hybrid systems is a flourishing area of research, which brings together chemistry, physics and materials science. These systems are composed of nanoparticles with interesting properties (e.g. optical, magnetic, catalytic) dispersed within an organic matrix. Control of both the position and orientation of the particles in a precise and reproducible way is an important goal. Towards this goal, the use of lyotropic liquid crystals as host phases is a promising strategy that has prompted sustained experimental work over the last decade. Here we briefly review this field, with an emphasis on the structure and the physical characterization of these novel materials.
Medical treatment of moderate to severe Crohn's disease (2003)

The treatment for patients with Crohn's disease of moderate to severe activity includes traditional drugs, such as corticosteroids, the primary therapy for these forms of disease, able to induce the remission of symptoms in a high percentage of patients. Because of the side-effects produced by systemic steroids, a new glucocorticoid derivative, budesonide, which acts locally in the mucosa, has recently been introduced with positive results. On the assumption that intestinal bacteria play a role in the causing Crohn's disease symptoms, antibiotics are often used in the treatment of active phases, as an alternative to or in association with steroids. The most widely employed antibiotics are metronidazole and ciprofloxacin. Immunosuppressors, such as azathioprine and 6-mercaptopurine, are useful for the treatment of chronic active disease and for maintaining remission, but they have only a marginal role in the therapy of an acute flare-up of Crohn's disease. Methotrexate acts more rapidly and its use in patients with active disease resistant to standard therapy is of interest. The discovery of biological agents represents a new era in the management of patients. To date, infliximab is the more extensively studied biological therapy in the treatment of Crohn's disease and clinical studies have demonstrated its efficacy in inducing remission of refractory disease.
Oversampling to Overcome Overfitting: Exploring the Relationship between Data Set Composition, Molecular Descriptors, and Predictive Modeling Methods (2013)

The traditional biological assay is very time-consuming, and thus the ability to quickly screen large numbers of compounds against a specific biological target is appealing. To speed up the biological evaluation of compounds, high-throughput screening is widely used in the fields of biomedical, biological information, and drug discovery. The research presented in this study focuses on the use of support vector machines, a machine learning method, various classes of molecular descriptors, and different sampling techniques to overcome overfitting to classify compounds for cytotoxicity with respect to the Jurkat cell line. The cell cytotoxicity data set is imbalanced (a few active compounds and very many inactive compounds), and the ability of the predictive modeling methods is adversely affected in these situations. Commonly imbalanced data sets are overfit with respect to the dominant classified end point; in this study the models routinely overfit toward inactive (noncytotoxic) compounds when the imbalance was substantial. Support vector machine (SVM) models were used to probe the proficiency of different classes of molecular descriptors and oversampling ratios. The SVM models were constructed from 4D-FPs, MOE (1D, 2D, and 21/2D), noNP+MOE, and CATS2D trial descriptors pools and compared to the predictive abilities of CATS2D-based random forest models. Compared to previous results in the literature, the SVM models built from oversampled data sets exhibited better predictive abilities for the training and external test sets.
Protective efficacy in humans of killed whole-vibrio oral cholera vaccine with and without the B subunit of cholera toxin (1987)

Natural protection from cholera is associated with local intestinal antibacterial and antitoxic antibodies, which appear to act synergistically. Although current parenteral cholera vaccines offer insufficient protection, new vaccines administered orally have more promise. Killed Vibrio cholerae, alone or given with the B subunit of cholera toxin, was evaluated in adult volunteers. Vaccinees, who received three doses of either vaccine, and unvaccinated controls ingested 10(6) V. cholerae organisms to determine the protective efficacy of the vaccines. The combination vaccine provided 64% protection, and the whole vibrio vaccine given alone provided 56% protection. In addition, illnesses in vaccines were milder than those in controls, and both vaccines gave complete protection against more severe disease. This substantial level of protection against a dose of V. cholerae that caused cholera in nearly 90% of controls suggests that these vaccines might provide at least as high a level of protection if given to the population of an endemic area. Indeed, a field efficacy trial is underway in Bangladesh, and preliminary data indicate a protective efficacy of 85% for a killed whole vibrio plus B subunit vaccine similar to that tested in volunteers and an efficacy of 58% for the killed whole vibrio vaccine alone. Thus, the studies in human volunteers were successful in predicting the substantial protection afforded by the vaccines in a cholera endemic area.
A Transient Analysis Method to Characterize the Trap Vertical Location in Nitride-Trapping Devices (2004)

A new method to probe the trap vertical location for nitride-trapping devices is proposed. This method requires only measuring the time dependence of gate injection at various gate voltages on a single wafer. The transient current (J) and the instantaneous electric field (E) across the top oxide can be directly obtained based on various cases of trap location. Comparisons can be made to check which case has the best consistency for the J versus E behaviors. The only assumption in this method is that the transient current J and the instantaneous E field should follow a consistent tunneling relationship at different gate voltages. The experimental results show unequivocally that electrons are trapped at the interface between top oxide and nitride for oxide grown by thermal conversion. However, for the direct-deposited top oxide the electrons are more spatially distributed in the nitride. This method is a simple and convincing tool to detect the nitride trap vertical location.
Cloning and chromosomal location of human alpha 1(XVI) collagen. (1992)

We have characterized cDNA clones that encode a newly discovered collagenous polypeptide. A 4-kilobase (kb) cDNA clone was initially isolated by screening a human fibroblast cDNA library with a probe encoding the collagenous domain of the human alpha 3(VI) collagen. Subsequent screening of another fibroblast cDNA library yielded overlapping clones having a total length of 5.4 kb, which contained an open reading frame of 1603 amino acids including a 21-amino acid signal peptide. The predicted polypeptide consists of 10 collagenous domains 15-422 amino acids long, which were interspersed with 11 noncollagenous (NC) domains. Except for a large N-terminal NC11 domain of 312 residues, most of the NC domains were short (11-39 residues) and cysteine-rich. The overall structural arrangement differed significantly from other known collagen chains. Further analysis indicated that the deduced polypeptide exhibited several structural features characteristically seen in members of the fibril-associated collagen, types IX, XII, and XIV. In addition, the cysteine-rich motifs in the NC domains resembled those found in the cuticle collagen of Caenorhabditis elegans. Northern blot analyses showed hybridization of the cDNA to a 5.5-kb mRNA in human fibroblasts and keratinocytes. The gene was localized by in situ hybridization to band p34-35 of human chromosome 1. The data clearly support the conclusion that the cDNA encodes a collagen chain that has not been previously described. We suggest that the cDNA clones encode the alpha 1 chain of type XVI collagen.
Differential extension of 3′ mispairs is a major contribution to the high fidelity of calf thymus DNA polymerase-α (1989)

The fidelity of DNA polymerase-alpha-primase from calf thymus has been analyzed by measuring mutagenesis in vitro and by site-specific nucleotide misinsertion and mispair extension. Using the phi X174 am3 DNA reversion assay errors are detected at the amber3 site only when both dATP and dCTP are significantly biased during in vitro copying reactions. Analysis of these products on DNA sequencing gels reveals pause sites due to the slow extension of mispaired 3' termini. Measurements of misinsertion rates opposite template A show that the rates of dAMP or dCMP misinsertion are similar and occur 40-50 times more rapidly than dGMP misinsertion. The rate of extension from an A:C mispair is 100- and 400-fold greater than from an A:A mispair and an A:G mispair, respectively. Nucleotide misinsertions to generate all 12 possible mispairs have been measured kinetically on phi X174 DNA templates that contain either A, C, G, or T at position 587. Misinsertion frequencies range from 1/4000 to 1/10(6) depending on the mispairs generated. Extension from all 12 different mispairs was examined by starting with oligonucleotide primers that contain different 3'-terminal mispairs. Rates of extension from mispairs are 10(3) to 10(6) times slower than from correctly paired bases. Extension frequencies were purine:pyrimidine greater than pyrimidine:pyrimidine greater than purine:purine. Lack of extension of misincorporated bases suggests the involvement of exonucleolytic proofreading to enable continued DNA synthesis and to guarantee the high fidelity of eucaryotic DNA replication.
Design and Optimization of Reverse-Transcription Quantitative PCR Experiments (2009)

We recommend the use of sample replicates preferentially to any other replicates when working with solid tissue, cell cultures, and single cells, and we recommend the use of RT replicates when working with blood. We show how an optimal sampling plan can be calculated for a limited budget. .
Understanding Data Augmentation for Classification: When to Warp? (2016)

In this paper we investigate the benefit of augmenting data with synthetically created samples when training a machine learning classifier. Two approaches for creating additional training samples are data warping, which generates additional samples through transformations applied in the data-space, and synthetic over-sampling, which creates additional samples in feature-space. We experimentally evaluate the benefits of data augmentation for a convolutional backpropagation-trained neural network, a convolutional support vector machine and a convolutional extreme learning machine classifier, using the standard MNIST handwritten digit dataset. We found that while it is possible to perform generic augmentation in feature-space, if plausible transforms for the data are known then augmentation in data-space provides a greater benefit for improving performance and reducing overfitting.
Identification of human tumor antigens and its implications for diagnosis and treatment of cancer (2004)

Human tumor antigens recognized by T cells have been identified by means of various molecular biological and immunological methods, including cDNA expression cloning with patients' T cells and antibodies, cDNA subtraction using RDA and PCR differential display, systematic gene analysis such as DNA sequencing, CGH, DNA chip/microarray and SAGE, in vitro T cell induction and immunization of HLA transgenic mice. The identification of human tumor antigens has led to a better understanding of the nature of tumor antigens, anti-tumor immune responses in patients before and after immunotherapy, and tumor escape mechanisms. The information obtained from these researches has enabled us to develop and improve immunotherapy by attempting to overcome the identified problems, including intrinsically low immunogenicity of tumor antigens and several escape mechanisms, such as regulatory T cell induction. The existence of immunogenic unique antigens derived from genetic alterations in tumor cells, and the varied immunogenicity of shared tumor antigens among patients due to differing expression in tumor cells and immunoreactivity of patients, indicates that individualized immunotherapy should ideally be performed. The identified antigens will also be useful for development of diagnostic methods and molecular targeting therapy for cancer.
Solute and penetrant diffusion in swellable polymers. II. Verification of theoretical models (1986)

Abstract A mathematical model developed to describe diffusion of a penetrant and a solute in a swellable polymer slab was applied to the case of a hydrophilic polymer loaded with a soluble drug in which the penetrant (water) is sorbed and solute (drug) is desorbed. An exponential dependence of the penetrant and solute diffusion coefficients on penetrant concentration was chosen and shown to be adequate for description of the systems studied. Experimental verification of the model was conducted by using copolymers of 2‐hydroxyethyl methacrylate (HEMA) and N ‐vinyl‐2‐pyrrolidone (NVP). The monomers were bulk polymerized with benzoyl peroxide initiator and cut into thin disks. Monomer mole fractions of HEMA in the copolymers were 0.707, 0.446, and 0.211. Swelling behavior of the samples was observed in water at 37 and 0°C. Solute‐containing samples were prepared and solute release from these samples into water was followed by monitoring the UV absorption of the release medium. The concentration dependence of the diffusivity of water and two model solutes, sodium trifluoroacetate and sodium heptafluorobutyrate, in the gels was studied by using the pulsed‐gradient spin‐echo NMR technique. The diffusivities measured by this technique followed the concentration dependence predicted by the free‐volume theory. The simple exponential dependence used in the model was an adequate approximation of this behavior in the case of a transient diffusion experiment.
Interleukin-1 beta and tumor necrosis factor-alpha synergistically stimulate nerve growth factor synthesis in rat mesangial cells (1991)

Recent evidence indicates that cytokines are potent inducers of nerve growth factor (NGF) expression both in peripheral tissues and the central nervous system and that NGF, in addition to its neurotrophic action, also acts as an immunoregulatory agent. It was of interest to investigate whether inflammatory cytokines affect NGF production in renal mesangial cells, which play a crucial role in the modulation of the local immune function in the glomerulus. Our results show that the simultaneous addition of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) elicited a marked (13-fold) increase of NGF protein released by cultured rat glomerular mesangial cells within 24 h, whereas IL-1 alpha in combination with TNF-alpha, as well as the cytokines alone, did not promote the synthesis of NGF. The synergistic effect was dose dependent (maximal at 1 nM) and due to enhanced gene expression, since the cytokine treatment caused a fivefold increase in NGF mRNA after 8 h. Stimulation of NGF synthesis was abolished by mepacrine and dexamethasone, indicating that phospholipase A2 may be involved in NGF regulation. Moreover, pretreatment of the cells with the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) abolished induction of NGF by cytokines; in contrast, the specific cyclooxygenase inhibitors indomethacin and diclofenac failed to modify NGF production. These data suggest that a lipoxygenase metabolite produced in response to IL-1 beta and TNF-alpha acts as a mediator in NGF gene expression. In conclusion, these findings support a model in which a cytokine cascade including NGF may play an important role in the pathophysiology of inflammatory renal diseases.