gebhart/patrepeval huggingface dataset:
Recombination in mouse L cells between DNA introduced into cells and homologous chromosomal sequences. (1985)

In this paper, we show that DNA added to mouse L cells by the calcium phosphate method can be inserted into the genome of those cells by homologous recombination. The insertion event is detected because it reconstructs a functional thymidine kinase (tk) gene from two defective genes that share 320 base pairs of homology. One of the genes is missing its 5' portion (tk delta 5') and is in the cell's chromosome, and the other is missing its 3' portion (tk delta 3') and is in the introduced DNA. Gene reconstruction by homologous insertion is relatively inefficient; approximately one Tk+ transformant is produced per 10(6) cells per 4 micrograms of added tk DNA, a frequency of about 10(-5) that of normal tk gene transformation. The Tk+ transformants produced by homologous recombination contain Sma I and Pvu II fragments that are diagnostic of the intact tk gene, contain a herpesvirus-specific thymidine kinase activity, and can transfer the Tk+ phenotype to Tk- cells by DNA-mediated gene transfer. Two surprising observations made in the course of these studies were that only 1 of 10 Tk- cell lines containing defective tk genes could be transformed to Tk+ by homologous insertion of the complementary defective tk gene and that relatively little illegitimate insertion of introduced tk DNA into cellular DNA was detected in those cells that were transformed to Tk+ by homologous recombination.
Human Zn‐α2‐glycoprotein cDNA cloning and expression analysis in benign and malignant breast tissues (1991)

Two cDNA clones coding for Zn-alpha 2-glycoprotein (Zn-alpha 2-gp) have been isolated from a human breast library and their nucleotide sequences determined. The deduced amino acid sequence contains the coding information for a hydrophobic signal peptide and the 278 residues of the mature protein. Comparison of this sequence with that from the protein purified from plasma reveals four differences: two amino acid changes (Gln-67 and Glu-222) and insertion of two residues (Ile-75 and Phe-76). Northern-blot analysis showed that the Zn-alpha 2-gp gene is expressed in liver and normal breast, but not in placenta, ovary and thyroid. A comparative analysis in mammary tissues from women with different diseases revealed enhanced expression of Zn-alpha 2-gp gene in benign breast lesions and a variable expression level in breast cancers.
Improved Preparation of Lipoteichoic Acids (1983)

A procedure is described for measuring the extraction of lipoteichoic acids from gram-positive bacteria in absolute terms. Virtually complete extraction was achieved from various bacteria by hot phenol/water if the cells were disrupted. Extraction of whole and delipidated cells and of the membrane fraction gave considerably lower yields. Most of the nucleic acids co-extracted from disrupted cells was removed by treatment with nucleases. Nuclease-resistant nucleic acid, protein, polysaccharide, and teichoic acid were separated from lipoteichoic acid by anionexchange chromatography on DEAE-Sephacel or hydrophobic interaction chromatography on octyl-Sepharose. Purified preparations were essentially free of polymeric contaminants, retained their alanine ester substitution, and were in the sodium salt form. Hydrophobic interaction chromatography also made it possible to recognize contamination of lipoteichoic acid with its deacylated and lyso-form, and to discriminate molecular species containing two and three, or two and four acyl groups.
The Role of Vitamin D in Cancer Prevention (2005)

Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects.
The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip (1991)

Clinical criteria for the classification of patients with hip pain associated with osteoarthritis (OA) were developed through a multicenter study. Data from 201 patients who had experienced hip pain for most days of the prior month were analyzed. The comparison group of patients had other causes of hip pain, such as rheumatoid arthritis or spondylarthropathy. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop different sets of criteria to serve different investigative purposes. Multivariate methods included the traditional "number of criteria present" format and "classification tree" techniques. Clinical criteria: A classification tree was developed, without radiographs, for clinical and laboratory criteria or for clinical criteria alone. A patient was classified as having hip OA if pain was present in combination with either 1) hip internal rotation greater than or equal to 15 degrees, pain present on internal rotation of the hip, morning stiffness of the hip for less than or equal to 60 minutes, and age greater than 50 years, or 2) hip internal rotation less than 15 degrees and an erythrocyte sedimentation rate (ESR) less than or equal to 45 mm/hour; if no ESR was obtained, hip flexion less than or equal to 115 degrees was substituted (sensitivity 86%; specificity 75%). Clinical plus radiographic criteria: The traditional format combined pain with at least 2 of the following 3 criteria: osteophytes (femoral or acetabular), joint space narrowing (superior, axial, and/or medial), and ESR less than 20 mm/hour (sensitivity 89%; specificity 91%). The radiographic presence of osteophytes best separated OA patients and controls by the classification tree method (sensitivity 89%; specificity 91%). The "number of criteria present" format yielded criteria and levels of sensitivity and specificity similar to those of the classification tree for the combined clinical and radiographic criteria set. For the clinical criteria set, the classification tree provided much greater specificity. The value of the radiographic presence of an osteophyte in separating patients with OA of the hip from those with hip pain of other causes is emphasized.
Efficacy of oral WIN 54954 for prophylaxis of experimental rhinovirus infection (1993)

The efficacy of oral WIN 54954 for the prevention of rhinovirus infection and illness was tested in two randomized, double-blinded, placebo-controlled volunteer challenge studies. Volunteers were inoculated with rhinovirus type 39 (MIC of WIN 54954, 0.17 microgram/ml) or rhinovirus type 23 (MIC, 0.016 microgram/ml). The volunteers received two doses of drug (600 mg per dose) or placebo on the first day; this was followed by three doses on each of the subsequent 5 days. All volunteers were challenged with virus after the third dose of study drug. No significant antiviral or clinical effect was detected in either study. Pharmacokinetic studies revealed that on the last day of drug administration, 38 of 39 (97%) volunteers had trough levels of WIN 54954 in plasma greater than the MIC for the respective virus. Nasal wash specimens collected on the same day revealed a detectable level in only 6 of 24 (25%) volunteers at the peak (range, 6 to 24 ng/ml) and in only 2 of 14 (14%) volunteers at the trough (range, 6 and 7 ng/ml). These results suggest that the lack of efficacy of WIN 54954 against rhinovirus may be related to an inability to deliver sufficient drug to the site of viral infection.
Ultrastrong coupling regime of cavity QED with phase-biased flux qubits (2009)

We theoretically study a circuit QED architecture based on a superconducting flux qubit directly coupled to the center conductor of a coplanar waveguide transmission-line resonator. As already shown experimentally [A. A. Abdumalikov, Jr. et al., Phys. Rev. B 78, 180502(R) (2008)], the strong coupling regime of cavity QED can readily be achieved by optimizing the local inductance of the resonator in the vicinity of the qubit. In addition to yielding stronger coupling with respect to other proposals for flux qubit based circuit QED, this approach leads to a qubit-resonator coupling strength $g$ which does not scale as the area of the qubit but is proportional to the total inductance shared between the resonator and the qubit. Strong coupling can thus be attained while still minimizing sensitivity to flux noise. Finally, we show that by taking advantage of the large kinetic inductance of a Josephson junction in the center conductor of the resonator can lead to coupling energies of several tens of percent of the resonator frequency, reaching the ultrastrong coupling regime of cavity QED where the rotating-wave approximation breaks down. This should allow an on-chip implementation of the $E\ensuremath{\bigotimes}\ensuremath{\beta}$ Jahn-Teller model.
Benjamin Franklin’s Metaphysical Essays and the Virtue of Humility (2013)

Historians have long rejected Max Weber and D. H. Lawrence’s portrayal of Benjamin Franklin as the stuffy architect of a new kind of prudish bourgeois virtue. Recent scholarly work has challenged this notion and has added something more: the idea that Franklin is a serious thinker, even an ironic thinker, in the Western philosophic tradition. Certainly Franklin participated in a vigorous intellectual debate with the greatest minds of his time over the meaning of religion, moral duty, and virtue. In this article I return to Franklin’s own writings to provide what I think is a new and hopefully provocative interpretation of Franklin as a philosophic thinker. After briefly recounting the traditional interpretation of Franklin’s Autobiography, I present new interpretations of Franklin’s metaphysical essays in the context of his orientation to the philosophical schools of his day and argue that Franklin, upon this foundation, constructs his own theory of the philosophical temper.
The contrast source inversion method for location and shape reconstructions (2002)

In this study we propose a multiplicative regularization scheme to deal with the problem of the detection and imaging of homogeneous dielectric objects (the so-called binary objects). By considering the binary regularizer as a multiplicative constraint for the contrast source inversion (CSI) method we are able to avoid the necessity of determining the regularization parameter before the inversion process has been started. We present some numerical results for some representative two-dimensional configurations, but we also show the three-dimensional reconstruction for a full vectorial electromagnetic problem. We conclude that the binary CSI method is able to obtain reasonable reconstruction results even when a wrong estimate of the material parameter is used. Moreover, generalization of the method allows us to handle inversion of more than one homogeneous scatterer having different material parameters.
Structure–Activity Relationships of SSAO/VAP‐1 Arylalkylamine‐Based Substrates (2009)

Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1) substrates show insulin-mimetic effects and are therefore potentially valuable molecules for the treatment of diabetes mellitus. Herein we review several structural and electronic aspects of SSAO arylalkylamine-based substrates. Two main modifications directly affect amine oxidase (AO) activity: 1) variation in ring substitution modulates the biological activity of the arylalkylamine ligand by converting a substrate into a substrate-like inhibitor, and 2) variation in the number of methylene units between the aromatic ring and the ammonium groups of the arylalkylamine substrates dramatically alters the oxidation rate between species. Furthermore, we review relevant information about mammalian SSAO/VAP-1 substrate selectivity and specificity over monoamine oxidases (MAOs).
Retrovirus‐Mediated Gene Transfer of the Human γ‐IFN Gene: A Therapy for Cancer (1994)

A retroviral vector-mediated gene transfer system was used to introduce m gamma-IFN and h gamma-IFN genes into mouse and human tumor cells, respectively. Murine tumor cell lines and primary human melanoma tumor cells were successfully transduced with gamma-IFN vector, and these transduced cells secreted measurable levels of biologically active m gamma-IFN and h gamma-IFN, respectively. Both murine and human tumor cell lines that expressed gamma-IFN exhibited increased surface expression of HLA class I antigens when tested by Western blot and FACS analysis. gamma-IFN--transduced human melanoma cells were more active in stimulating tumor-specific cytolytic activity of CTLs from melanoma patients in vitro. m gamma-IFN--transduced tumor cells were substantially less tumorigenic than the corresponding parent tumor cell lines in immune-competent mice. In addition, injection of m gamma-IFN--transduced tumor cells resulted in activation of tumor-specific CTL in vivo. We plan to use gamma-IFN--transduced autologous tumor cells to boost host immune responses as a potential therapy for human melanoma.
AMPA receptor desensitization predicts the selective vulnerability of cerebellar Purkinje cells to excitotoxicity (1995)

Cerebellar Purkinje cells are selectively vulnerable to ischemia, although the reasons for this are unknown. In cultured embryonic rat cerebellar neurons, the steady state responses to the desensitizing agonist AMPA relative to responses to the nondesensitizing agonist kainate were greater in Purkinje cells compared to other cells, as measured by whole cell voltage clamp studies. Fluorimetric [Ca2+]i imaging experiments similarly found greater responses to AMPA relative to kainate in Purkinje cells than in other cerebellar neurons. In toxicity experiments measuring cell survival 24 hr following agonist exposure, AMPA and glutamate produced Ca(2+)-dependent toxicity which was selective for the Purkinje cell fraction of the neurons, whereas kainate produced nonselective toxicity, and NMDA selectively spared the mature Purkinje cells. Cyclothiazide, which inhibits AMPA receptor desensitization, enhanced steady state current responses to AMPA and increased the toxicity of AMPA. We conclude that the vulnerability of cerebellar neurons in culture to glutamate agonist-induced toxicity parallels the magnitude of the steady state currents produced, and that Purkinje cells may be selectively vulnerable because they express AMPA receptors which undergo less complete desensitization.
Ex vivo coating of islet cell allografts with murine CTLA4/Fc promotes graft tolerance (1995)

To test the hypothesis that blockade of B7-triggered costimulation by donor cells could preclude allograft rejection, we coated crude islet allograft preparations in vitro for 1 h with a murine CTLA4/Fc fusion protein. Murine CTLA4/Fc blocks the proliferative response in primary mixed lymphocyte cultures (MLC) and Con A-stimulated murine spleen cell cultures by 85 to 95%. Responder cells from a primary MLC containing mCTLA4/Fc were hyporesponsive upon restimulation to the same stimulator cells in a secondary MLC lacking mCTLA4/Fc. Because of mutations in the Fc gamma RI and C'1q binding sites of the Fc portion of the murine CTLA4/Fc fusion protein, the molecule binds to, but does not target, cells for Ab-dependent cellular cytotoxicity or complement-directed cytolysis. Although systemic immunosuppression was not applied, 42% (10 of 24) of B6AF1 recipients of islet allografts pretreated with CTLA4/Fc were permanently engrafted. Further, 50% of hosts bearing functioning islet allografts more than 150 days post-transplant were formally proved to be tolerant to donor tissues. A persistent CD4+ and CD8+ T cell infiltrate surrounding, but not invading, islet grafts in tolerant hosts was discerned. In control experiments, 89% (8 of 9) of islet allografts coated with mIgG3, and 100% (n = 10) pretreated with media alone were rejected. Thus, we conclude that 1) B7-triggered costimulation by donor APCs is an important element of rejection, and 2) blockade of the B7 pathway by in vitro allograft manipulation is able to induce tolerance.
The p38 Mitogen-Activated Protein Kinase Signaling Pathway Is Coupled to Toll-Like Receptor 5 To Mediate Gene Regulation in Response toPseudomonas aeruginosaInfection in Human Airway Epithelial Cells (2007)

In this study, we show that stimulation of human airway epithelial cells (HAECs) by Pseudomonas aeruginosa strain PAO1 induces time- and dose-dependent activation of p38 mitogen-activated protein kinase (MAPK). Activated p38 MAPK stayed in the cytoplasm instead of translocating to the nucleus, as shown by cellular fractionation. p38 MAPK was activated when HAECs were incubated with P. aeruginosa strain PAK and Burkholderia cepacia, while little activation was observed with the isogenic flagellin-free strains PAK/fliC and B. cepacia BC/fliC. The presence of Toll-like receptor 5 (TLR5) in 293 cells mediated PAO1-dependent activation of p38 MAPK, and in HAECs p38 MAPK activation was blocked by the overexpression of a dominant negative TLR5. Two inhibitors of p38 MAPK, SB202190 and SB203580, significantly attenuated PAO1-dependent expression of an NF-kappaB-dependent luciferase reporter gene, suggesting that p38 MAPK activation is required for full activation of NF-kappaB-dependent signaling. Microarray analysis of NF-kappaB target genes revealed up-regulation of multiple genes by PAO1 in HAECs. Reverse transcription-PCR and protein expression analysis were used to show that up-regulation of NF-kappaB-dependent genes induced by PAO1, such as the genes encoding Cox-2 and interleukin-8, was attenuated by SB203580. These results demonstrate a role for p38 MAPK signaling in gene regulation in response to P. aeruginosa via TLR5.
A systems view of mRNP biology (2004)

Gene expression occurs through a complex mRNA-protein (mRNP) system that stretches from transcription to translation. Gene expression processes are increasingly studied from global perspectives in order to understand their pathways, properties, and behaviors as a system. Here we review these beginnings of mRNP systems biology, as they have emerged from recent large-scale investigation of mRNP components, interactions, and dynamics. Such work has begun to lay the foundation for a broader, integrated view of mRNP organization in gene expression.
On-demand electrohydrodynamic jetting with meniscus control by a piezoelectric actuator for ultra-fine patterns (2009)

The on-demand ejection of ultra-fine droplets that uses both an electrohydrodynamic (EHD) force and mechanical actuation is presented. The liquid meniscus was controlled by a piezoelectric actuator, and the droplets were ejected by the EHD force. Through these effects, it was possible to obtain a high operational jetting frequency of 1 kHz with a short delay time (about 50 µs) in comparison with existing on-demand, EHD jetting methods, such as the pulsating jet mode (3–10 ms) and the pulsed cone–jet mode (3.6 ms). Simultaneously, we obtained ultra-fine droplets through adjustments of the piezoelectric driving waveform. The jetting characteristics were examined for both the hydrophobicity and the hydrophilicity of the surface of a capillary.
Derivation, Maintenance, and Characterization of Rat Embryonic Stem Cells In Vitro (2006)

The in vitro differentiation of mouse embryonic stem (ES) cells into different somatic cell types such as neurons, endothelial cells, or myocytes is well established, and many mouse ES cell lines have been created so far. The establishment of rat ES cell lines, however, has proven to be difficult. Most attempts to culture rat ES cell lines and maintain them in an undifferentiated state have failed, so researchers were forced to abandon this system and use mouse ES cells. This chapter describes the long-term cultivation of an alkaline phosphatase-positive rat embryonic stem cell-like line (RESC) and their differentiation into neuronal, endothelial, and hepatic lineages. The RESCs can be characterized by typical growth in single cells as well as embryoid bodies when cultivated in the presence of leukemia inhibitory factor. RESC expressed stage-specific-embryonic antigen 1 and the major histocompatibility class 1 molecule. Neuronal differentiation is achieved by standard retinoic acid treatment and endothelial differentiation can be reproducibly induced by growth on or within Matrigel for 14 d. To induce expression of hepatocyte-specific antigens, RESCs were either grown in hepatocyte-conditioned media or in media containing different combinations of growth factors. The characterization of differentiated cells was done primarily by immunohistochemistry, enzyme-linked immunosorbent assay, and polymerase chain reaction.
A mutation in CSE4, an essential gene encoding a novel chromatin-associated protein in yeast, causes chromosome nondisjunction and cell cycle arrest at mitosis. (1995)

The centromere, a differentiated region of the eukaryotic chromosome, mediates the segregation of sister chromatids at mitosis. In this study, a Saccharomyces cerevisiae chromosome mis-segregation mutant, cse4-1, has been isolated and shown to increase the nondisjunction frequency of a chromosome bearing a mutant centromere DNA sequence. In addition, at elevated temperatures the cse4-1 allele causes a mitosis-specific arrest with a predominance of large budded cells containing single G2 nuclei and short bipolar mitotic spindles. The wild-type gene, CSE4, is essential for cell division and encodes a protein containing a domain that is 64% identical to the highly conserved chromatin protein, histone H3. Biochemical experiments demonstrate that CSE4p has similar DNA-binding characteristics as those of histone H3 and might form a specialized nucleosome structure in vivo. Interestingly, the human centromere protein, CENP-A, also contains this H3-like domain. Data presented here indicate that CSE4p is required for proper kinetochore function in yeast and may represent an evolutionarily conserved protein necessary for assembly of the unique chromatin structure associated with the eukaryotic centromere.
Vascularization Strategies for Tissue Engineering (2009)

Tissue engineering is currently limited by the inability to adequately vascularize tissues in vitro or in vivo. Issues of nutrient perfusion and mass transport limitations, especially oxygen diffusion, restrict construct development to smaller than clinically relevant dimensions and limit the ability for in vivo integration. There is much interest in the field as researchers have undertaken a variety of approaches to vascularization, including material functionalization, scaffold design, microfabrication, bioreactor development, endothelial cell seeding, modular assembly, and in vivo systems. Efforts to model and measure oxygen diffusion and consumption within these engineered tissues have sought to quantitatively assess and improve these design strategies. This review assesses the current state of the field by outlining the prevailing approaches taken toward producing vascularized tissues and highlighting their strengths and weaknesses.
Toward a Biosignature for Suicide (2014)

The most compelling biomarkers for suicide are linked to altered stress responses and their downstream effects, and to abnormalities in the serotonergic system. Studying these systems in parallel and in the same populations may elucidate the role of each and their interplay, possibly leading to identification of new treatment targets and biological predictors.