gebhart/patrepeval huggingface dataset:
Differentiated structure and function of cultures from human tracheal epithelium (1992)

Here we describe the conditions which allow cultured human tracheal epithelial cells to retain the ion transport properties and ultrastructure of the original tissue. The order of potency of growth supports and media additives in elevating baseline short-circuit current (Isc) and responses to mediators were vitrogen gel (VIT) greater than extracellular matrix from bovine corneal endothelial cells (ECM) greater than human placental collagen (HPC), and 2% Ultroser G serum substitute (USG) greater than 5% fetal calf serum (FCS) greater than defined growth factors (GF). For all combinations of medium and growth supports, an air interface (AIR) gave better electrical properties than immersion feeding (IMM). As opposed to our earlier conditions (HPC/FCS/IMM), the best new combination (VIT/USG/AIR) produced higher baseline Isc (58.0 +/- 10.6 vs. 5.1 +/- 1.0 microA/cm2) and increased Isc responses to isoproterenol (6.1 +/- 1.5 vs. 0.8 +/- 0.3 microA/cm2) and bradykinin (9.6 +/- 2.0 vs. 1.0 +/- 0.2 microA/cm2), while retaining high transepithelial resistance (227 +/- 5 omega.cm2). VIT/USG/AIR led to the appearance of cilia, an increase in the depth of the cell sheets (50 vs. 10 microns), longer and more frequent apical microvilli, and increased interdigitations of the basolateral membrane. Protein and DNA content were also significantly increased. Secretory granules were present which stained with antibody to goblet cells, but not to serous or mucous gland cells. CF cells grown in VIT/USG/AIR showed high baseline Isc (69 +/- 18 microA/cm2) and a proportionately larger inhibition of Isc by amiloride (70 +/- 10 vs. 34 +/- 3%). Isc did not respond to isoproterenol, and the response to bradykinin was 22% normal.
Encapsulation of Submicrometer-Sized 2-Methoxyestradiol Crystals into Polymer Multilayer Capsules for Biological Applications (2006)

A facile approach has been developed to encapsulate submicrometer-sized drug crystals into polymer multilayer capsules produced by sequential deposition of polymers onto the drug particle surfaces. 2-Methoxyestradiol (2-ME) is a hydrophobic metabolite of 17-beta estradiol, which has been demonstrated as a potential anticancer agent. It was selected as a model drug and was formulated into submicrometer-sized particles through fine milling followed by intense sonication in the presence of dipalmitoyl-dl-(R)-phosphatidylcholine (DPPC). The reserved positive charges on the 2-ME crystal surface by DPPC enhanced the water solubility of the particles and subsequent self-assembly of dextran sulfate (DS) and dextran (DN) multilayers through hydrogen bonding and physical adsorption. Upon the exposure of the drug capsules to ethanol, hollow DS/DN multilayer polymer shells can be formed. The encapsulation process and hollow polymer multilayer shell formation were confirmed by confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM), while the surface morphology of the formed drug capsules was investigated using scanning electron microscopy (SEM). In vitro studies show that the inhibitory effect of the formed 2-ME capsules is the same as that of the conventional formulation of 2-ME in a concentrated ethanol solution, as demonstrated by dramatic changes in cell morphology and significantly decreased viability of target cells. We also demonstrate that the change of the outermost layer of the drug capsules does not significantly influence its bioactivity. The presented strategy to encapsulate submicrometer-sized hydrophobic drug particles is expected to provide a general pathway to fabricate drug capsules for various biological applications.
Dominant missense mutations in a novel yeast protein related to mammalian phosphatidylinositol 3-kinase and VPS34 abrogate rapamycin cytotoxicity. (1993)

Rapamycin is a macrolide antifungal agent that exhibits potent immunosuppressive properties. In Saccharomyces cerevisiae, rapamycin sensitivity is mediated by a specific cytoplasmic receptor which is a homolog of human FKBP12 (hFKBP12). Deletion of the gene for yeast FKBP12 (RBP1) results in recessive drug resistance, and expression of hFKBP12 restores rapamycin sensitivity. These data support the idea that FKBP12 and rapamycin form a toxic complex that corrupts the function of other cellular proteins. To identify such proteins, we isolated dominant rapamycin-resistant mutants both in wild-type haploid and diploid cells and in haploid rbp1::URA3 cells engineered to express hFKBP12. Genetic analysis indicated that the dominant mutations are nonallelic to mutations in RBP1 and define two genes, designated DRR1 and DRR2 (for dominant rapamycin resistance). Mutant copies of DRR1 and DRR2 were cloned from genomic YCp50 libraries by their ability to confer drug resistance in wild-type cells. DNA sequence analysis of a mutant drr1 allele revealed a long open reading frame predicting a novel 2470-amino-acid protein with several motifs suggesting an involvement in intracellular signal transduction, including a leucine zipper near the N terminus, two putative DNA-binding sequences, and a domain that exhibits significant sequence similarity to the 110-kDa catalytic subunit of both yeast (VPS34) and bovine phosphatidylinositol 3-kinases. Genomic disruption of DRR1 in a mutant haploid strain restored drug sensitivity and demonstrated that the gene encodes a nonessential function. DNA sequence comparison of seven independent drr1dom alleles identified single base pair substitutions in the same codon within the phosphatidylinositol 3-kinase domain, resulting in a change of Ser-1972 to Arg or Asn. We conclude either that DRR1 (alone or in combination with DRR2) acts as a target of FKBP12-rapamycin complexes or that a missense mutation in DRR1 allows it to compensate for the function of the normal drug target.
Implication of nanoparticles/microparticles in mucosal vaccine delivery (2007)

Although polymeric nanoparticles/microparticles are well established for the mucosal administration of conventional drugs, they have not yet been developed commercially for vaccine delivery. The limitation of the mucosal (particularly oral) route of delivery, including low pH, gastric enzymes, rapid transit and poor absorption of large molecules, has made mucosal vaccine delivery challenging. Nevertheless, several polymeric delivery systems for mucosal vaccine delivery are currently being evaluated. The polymer-based approaches are designed to protect the antigen in the gut, to target the antigen to the gut-associated lymphoid tissue or to increase the residence time of the antigen in the gut through bioadhesion. M-cell targeting is a potential approach for mucosal vaccine delivery, which can be achieved using M-cell-specific lectins, microbial adhesins or immunoglobulins. While many hurdles must be overcome before targeted mucosal vaccine delivery becomes a practical reality, this is a potential area of research that has important implications for future vaccine development. This review comprises various aspects that could be decisive in the development of polymer based mucosal vaccine delivery systems.
Public Key Infrastructure Study (1994)

The National Institute of Standards and Technology (NIST) has tasked The MITRE Corporation to study the alternatives for automated management of public keys and of the associated public key certificates for the Federal Government. The public keys are envisioned to be used for secure electronic commerce. This Public Key Infrastructure (PKI) study focuses on the United States Federal Government operations, but also addresses national and global issues in order to facilitate the interoperation of protected electronic commerce among the various levels of government in the U.S., private citizens, commercial organizations, and international organizations. Under the PKI study, policy and legal issues related to the operation and the management of the PKI are identified. Architectural and implementation alternatives for the PKI are developed. In addition, a methodology to determine the cost of the PKI is presented. The results of the PKI study are documented in this report. With the information and techniques presented in this report, federal agencies will be able to determine which infrastructure alternative is appropriate to their needs. In addition, agencies may use the costing methodology presented in the paper for planning and budgeting purposes.
Mismatch repair in Xenopus egg extracts: DNA strand breaks act as signals rather than excision points. (1996)

In Xenopus egg extracts, DNA strand breaks (nicks) located 3' or 5' to a mismatch cause an overall 3-fold stimulation of the repair of the mismatch in circular heteroduplex DNA molecules. The increase in mismatch repair is almost entirely due to an increase in repair of the nicked strand, which is stimulated 5-fold. Repair synthesis is centered to the mismatch site, decreases symmetrically on both sides, and its position is not significantly altered by the presence of the nick. Therefore, it appears that in the Xenopus germ cells, the mismatch repair system utilizes nicks as signals for the induction and direction of mismatch repair, but not as the start or end point for excision and resynthesis.
Current Treatment Limitations in Age-Related Macular Degeneration and Future Approaches Based on Cell Therapy and Tissue Engineering (2014)

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein.
NET EMISSIONS OF CH4AND CO2IN ALASKA: IMPLICATIONS FOR THE REGION'S GREENHOUSE GAS BUDGET (2007)

We used a biogeochemistry model, the Terrestrial Ecosystem Model (TEM), to study the net methane (CH4) fluxes between Alaskan ecosystems and the atmosphere. We estimated that the current net emissions of CH4 (emissions minus consumption) from Alaskan soils are approximately 3 Tg CH4/yr. Wet tundra ecosystems are responsible for 75% of the region's net emissions, while dry tundra and upland boreal forests are responsible for 50% and 45% of total consumption over the region, respectively. In response to climate change over the 21st century, our simulations indicated that CH4 emissions from wet soils would be enhanced more than consumption by dry soils of tundra and boreal forests. As a consequence, we projected that net CH4 emissions will almost double by the end of the century in response to high-latitude warming and associated climate changes. When we placed these CH4 emissions in the context of the projected carbon budget (carbon dioxide [CO2] and CH4) for Alaska at the end of the 21st century, we estimated that Alaska will be a net source of greenhouse gases to the atmosphere of 69 Tg CO2 equivalents/yr, that is, a balance between net methane emissions of 131 Tg CO2 equivalents/yr and carbon sequestration of 17 Tg C/yr (62 Tg CO2 equivalents/yr).
Bone marrow transplantation in multiple myeloma (1999)

Experience from around the world now suggests that high response rates can be achieved in patients with multiple myeloma treated with high-dose therapy followed by hematopoietic stem cell transplantation. However, patients are destined to relapse and few, if any, are cured. Major obstacles to cure are the excessive toxicity noted after allografting in multiple myeloma, contaminating tumor cells in multiple myeloma autografts, and most importantly, the persistence of minimal residual disease after high-dose therapy and either allogeneic or autologous stem cell transplantation. In this context, strategies are being developed to decrease the toxicity of allografting and to enhance allogeneic anti-multiple myeloma immunity after transplantation to improve outcome. To improve autografting, better ablative regimens, more efficacious purging of tumor cells from autografts, and enhancement of autologous anti-multiple myeloma immunity post-transplantation are modalities being tested to enhance overall and event-free survival.
Chemokine and chemokine receptor analysis reveals elevated interferon-inducible protein-10 (IP)-10/CXCL10 levels and increased number of CCR5+ and CXCR3+ CD4 T cells in synovial fluid of patients with enthesitis-related arthritis (ERA) (2007)

Chemokines and chemokine receptors play a major role in homing of cells to the site of inflammation. Enthesitis-related arthritis (ERA) is a chronic inflammatory arthritis and no data are available on chemokines and their receptors in ERA. Blood (20) and synovial fluid (SF) (11) was collected from patients with ERA, and peripheral blood (PB) was collected from 12 patients with polyarticular juvenile idiopathic arthritis (JIA), nine patients with systemic onset and 18 healthy controls. Chemokines [interleukin (IL)-10/CXCL10, thymus and activation-regulated chemokine (TARC)/CCL17 and regulated upon activation normal T cell expressed and secreted (RANTES)/CCL5] were measured in serum and SF. Chemokine receptor expression was measured by flow cytometry. There was no difference in blood CD4(+) T cells bearing CCR5, CCR4 and CXCR3 in ERA and healthy controls. In paired samples the median frequency of CCR5(+) CD4(+) T cells was higher in SF compared to PB (15.8 versus 3.9%, P < 0.005), as was the frequency of CXCR3(+) T cells (21.61% versus 12.46%, P < 0.05). Median serum interferon-inducible protein-10 (IP-10)/CXCL10 levels were higher in patients with ERA compared to controls (139 versus 93 pg/ml; P < 0.05). Further median SF IP-10/CXCL10 levels were higher than the serum levels (2300 pg/ml versus 139 pg/ml; P < 0.01). Serum levels of RANTES/CCL5 were higher in patients (150 ng/ml) compared to control (99 ng/ml; P < 0.01). The SF levels were significantly lower compared to serum (P < 0.05). TARC/CCL17 levels in SF were lower than serum. There is increased homing of CCR5 and CXCR3(+) CD4 cells to the SF. Increased SF levels of IP-10/CXCL10 may be responsible for this migration in patients with ERA.
Hiding behind Hydrophobicity (2004)

Proteomics of membrane proteins is essential for the understanding of cellular function. However, mass spectrometric analysis of membrane proteomes has been less successful than the proteomic determination of soluble proteins. To elucidate the mystery of transmembrane proteins in mass spectrometry, we present a detailed statistical analysis of experimental data derived from chloroplast membranes. This approach was further accomplished by the analysis of the Arabidopsis thaliana proteome after in silico digestion. We demonstrate that both the length and the hydrophobicity of the proteolytic fragments containing transmembrane segments are major determinants for detection by mass spectrometry. Based on a comparative analysis, we discuss possibilities to overcome the problem and provide possible protocols to shift the hydrophobicity of transmembrane segment-containing peptides to facilitate their detection.
Neuroprotective and neurorestorative properties of GDNF (1998)

Glial cell line-derived neurotrophic factor (GDNF) promotes recovery of the injured nigrostriatal dopamine system and improves motor functions in both rodent and nonhuman primate models of Parkinson's disease (PD). The neurorestorative effects of a single administration of GDNF last for at least 1 month and can be maintained in rhesus monkeys by monthly injections. Adult midbrain dopamine neurons stimulated by GDNF show increased cell size, neurite extent, and expression of phenotypic markers. In parkinsonian nonhuman primates, GDNF treatment improves three of the cardinal features of PD: bradykinesia, rigidity, and postural instability. Although intracerebral administration is necessary because of the blood-brain barrier, intraventricular, intrastriatal, and intranigral routes of administration have been found to be efficacious in rodents and nonhuman primates. GDNF also induces neuroprotective changes in dopamine neurons which are active within hours after trophic factor administration. The powerful neuroprotective and neurorestorative properties of GDNF seen in preclinical studies suggest that trophic factors may play an important role in treating PD.
Roseburia cecicola gen. nov., sp. nov., a Motile, Obligately Anaerobic Bacterium from a Mouse Cecum (1983)

Strain GMT (type strain), a motile, obligately anaerobic bacterium, was isolated from scrapings of the cecal mucosa of a conventional laboratory mouse. Strain GMT cells were gram-negative, nonsporeforming, slightly curved rods (0.5 by 2.5 to 5 μm) with 20 to 35 flagella inserted into the concave side and, occasionally, into the end of each cell. The flagella appeared as a single fascicle when the cells were examined by phase-contrast microscopy. Glycerol, sorbitol, d-glucuronic acid, d-xylose, d-galactose, d-raffinose, d-glucose, d-maltose, cellobiose, sucrose, starch, and glycogen were growth substrates for this organism. Butyrate, ethanol, CO2, and H2 were products of fermentation of glucose and acetate by growing cells. The guanine-plus-cytosine content of the deoxyribonucleic acid of strain GMT was 42.3 mol%, as determined by the thermal denaturation method. The characteristics of this bacterium indicate that it does not belong to any currently recognized genus. Therefore, for this organism we propose a new genus, Roseburia, and a new species, Roseburia cecicola, in the family Bacteroidaceae. A culture of the type strain (strain GM) has been deposited in the American Type Culture Collection under the number ATCC 33874.
Lazy code motion (1992)

We present a bit-vector algorithm for the optimal and economical placement of computations within flow graphs, which is as efficient as standard uni-directional analyses. The point of our algorithm is the decomposition of the bi-directional structure of the known placement algorithms into a sequence of a backward and a forward analysis, which directly implies the efficiency result. Moreover, the new compositional structure opens the algorithm for modification: two further uni-directional analysis components exclude any unnecessary code motion. This laziness of our algorithm minimizes the register pressure, which has drastic effects on the run-time behaviour of the optimized programs in practice, where an economical use of registers is essential.
Protein Orientation in the Tat-TAR Complex Determined by Psoralen Photocross-linking (1996)

Replication of human immunodeficiency virus type 1 (HIV-1) requires specific interactions of Tat protein with the trans-activation responsive region (TAR) RNA, a 59-base stem-loop structure located at the 5'-end of all HIV mRNAs. We have used a new method based on psoralen photochemistry to identify a specific contact between a fragment of Tat protein (residues 38-72) and TAR RNA. We synthesized a 35-amino acid fragment containing arginine-rich RNA-binding domain of Tat (38-72), and replaced Arg57 with Cys to introduce a unique thiol group (-SH) in our model peptide. A psoralen derivative, which can react with thiol groups, was synthesized and used for specific chemical modification of Cys57-Tat-(38-72). We used this psoralen-Tat conjugate (psoralen-Cys57-Tat-(38-72)) to form a specific complex with TAR RNA. Upon near-ultraviolet irradiation (360 nm), this synthetic psoralen-peptide cross-linked to a single site in the TAR RNA sequence. The RNA-protein complex was purified and the cross-link site on TAR RNA was determined by RNA sequencing, which revealed that Cys57 of Tat is close to U31 of TAR RNA. Our results provide high-resolution proximity and orientation information about Tat-TAR complex. Such psoralen-peptide conjugates provide a new class of probes for sequence-specific protein-nucleic acid interactions and could be used to selectively control gene expression or to induce site-directed mutations.
Cloning, characterization, and functional expression of acs, the gene which encodes acetyl coenzyme A synthetase in Escherichia coli (1995)

Acetyl coenzyme A synthetase (Acs) activates acetate to acetyl coenzyme A through an acetyladenylate intermediate; two other enzymes, acetate kinase (Ack) and phosphotransacetylase (Pta), activate acetate through an acetyl phosphate intermediate. We subcloned acs, the Escherichia coli open reading frame purported to encode Acs (F. R. Blattner, V. Burland, G. Plunkett III, H. J. Sofia, and D. L. Daniels, Nucleic Acids Res. 21:5408-5417, 1993). We constructed a mutant allele, delta acs::Km, with the central 0.72-kb BclI-BclI portion of acs deleted, and recombined it into the chromosome. Whereas wild-type cells grew well on acetate across a wide range of concentrations (2.5 to 50 mM), those deleted for acs grew poorly on low concentrations (< or = 10 mM), those deleted for ackA and pta (which encode Ack and Pta, respectively) grew poorly on high concentrations (> or = 25 mM), and those deleted for acs, ackA, and pta did not grow on acetate at any concentration tested. Expression of acs from a multicopy plasmid restored growth to cells deleted for all three genes. Relative to wild-type cells, those deleted for acs did not activate acetate as well, those deleted for ackA and pta displayed even less activity, and those deleted for all three genes did not activate acetate at any concentration tested. Induction of acs resulted in expression of a 72-kDa protein, as predicted by the reported sequence. This protein immunoreacted with antiserum raised against purified Acs isolated from an unrelated species, Methanothrix soehngenii. The purified E. coli Acs then was used to raise anti-E. coli Acs antiserum, which immunoreacted with a 72-kDa protein expressed by wild-type cells but not by those deleted for acs. When purified in the presence, but not in the absence, of coenzyme A, the E. coli enzyme activated acetate across a wide range of concentrations in a coenzyme A-dependent manner. On the basis of these and other observations, we conclude that this open reading frame encodes the acetate-activating enzyme, Acs.
Nucleic Acid Hybridization (2005)

Abstract Nucleic acid hybridization allows the identification of homologous DNA and RNA sequences. This technique is used for gene mapping, gene expression studies and analysis of genomic organization.
Hemadsorption by colonies of Ureaplasma urealyticum (1991)

Hemadsorption by colonies of Ureaplasma urealyticum and Mycoplasma pneumoniae differed quantitatively and qualitatively. Using standard methodology, few strains of U. urealyticum hemadsorbed; with a modified method, most strains hemadsorbed, indicating a second type of association. Scanning electron microscopy of tannin-osmium-stained preparations showed guinea pig erythrocytes embedded in ureaplasma colonies and craters left when erythrocytes were dislodged.