gebhart/patrepeval huggingface dataset:
Assessment of the Opsonic Activity of Purified Bovine sIgA Following Intramammary Immunization of Cows with Staphylococcus aureus (2003)

The phagocytosis of Staphylococcus aureus by bovine polymorphonuclear neutrophils (PMN) requires the presence of antibodies. Among the major isotypes of bovine antibodies, IgG2 and IgM are considered opsonic for bovine PMN. However, the role of purified bovine secretory IgA (sIgA) as an opsonin has not been assessed. In the present study, IgG2 were obtained from serum and sIgA, IgG1, and IgM were purified from the colostrums of three cows intramammarily immunized with heat-killed Staphylococcus aureus. The Ig preparations were assayed for specific antibodies, and the opsonic capacity of every isotype was investigated. Despite the presence of antibodies, we observed no distinct chemiluminescence response of PMN stimulated with sIgA- or IgG1-opsonized S. aureus, whereas IgM or IgG2 bound to bacteria induced a marked chemiluminescence response. Moreover, the counting of internalized bacteria per PMN after phagocytosis revealed a low uptake of S. aureus opsonized with sIgA or IgG1, in contrast to IgM or IgG2, which triggered efficient ingestion of bacteria. Priming of neutrophils by TNF-alpha, IFN-gamma, or C5adesArg did not promote an oxidative burst or uptake of sIgA-opsonized S. aureus to a greater extent than with IgG1-opsonized bacteria. Furthermore, analysis of uningested bacteria by flow cytometry after incubation with PMN showed a preferential uptake of IgM-opsonized S. aureus by PMN and only few sIgA-positive stained bacteria were PMN-associated. These experiments indicate that sIgA, like IgG1 and unlike IgM or IgG2, could not be considered as a major opsonin for phagocytosis of S. aureus by bovine blood PMN.
TNF α is Important in Human Lung Allergic Reactions (1996)

Tumor necrosis factor alpha (TNF alpha) is a potentially important cytokine in allergic respiratory reactions since it is released by mast cells and eosinophils, and it can promote mediator and cytokine release, adhesion molecule expression, and granulocyte migration. Therefore, we induced an IgE-mediated response in human lung samples and studied: (1) whether TNF alpha was produced in sufficient quantities to promote granulocyte migration; and (2) which cells expressed mRNA for TNF alpha using in situ hybridization. Lung fragments (from thoracotomy) were treated for 30 min with either anti-IgE, 1:100 dilution, or buffer (control). Anti-IgE treatment of 16 lungs resulted in greater than 4-fold increase in histamine release and the significant production of chemotactic activity. The chemotactic activity generated induced dose-responsive neutrophil and eosinophil migration through naked filters and endothelial and pulmonary epithelial monolayers. Fourteen of 16 samples had a significant increase in TNF alpha subsequent to anti-IgE treatment (P < 0.05). Anti-TNF alpha antibody (4 micrograms/ml) inhibited about 25% of the neutrophil chemotactic activity in supernatants from anti-IgE treated lungs. TNF alpha at a concentration measured after anti-IgE treatment of lung samples (50 pg/ml) induced neutrophil transendothelial migration. Finally, we found that anti-IgE treatment led to an increase in TNF alpha mRNA-positive cells by in situ hybridization (1.6/ mm2 experimental versus 0.5/mm2 control), some of which were eosinophils. Thus, human lung IgE-mediated responses in vitro results in: (1) release of TNF alpha in amounts sufficient to effect a biologic response, granulocyte chemotaxis: and (2) upregulation of mRNA for TNF alpha in eosinophils and other cells. These findings suggest that TNF alpha is an important effector molecule in the pathogenesis of allergic respiratory reactions.
Sequencing by Cyclic Ligation and Cleavage (CycLiC) directly on a microarray captured template (2008)

Next generation sequencing methods that can be applied to both the resequencing of whole genomes and to the selective resequencing of specific parts of genomes are needed. We describe (i) a massively scalable biochemistry, Cyclical Ligation and Cleavage (CycLiC) for contiguous base sequencing and (ii) apply it directly to a template captured on a microarray. CycLiC uses four color-coded DNA/RNA chimeric oligonucleotide libraries (OL) to extend a primer, a base at a time, along a template. The cycles comprise the steps: (i) ligation of OLs, (ii) identification of extended base by label detection, and (iii) cleavage to remove label/terminator and undetermined bases. For proof-of-principle, we show that the method conforms to design and that we can read contiguous bases of sequence correctly from a template captured by hybridization from solution to a microarray probe. The method is amenable to massive scale-up, miniaturization and automation. Implementation on a microarray format offers the potential for both selection and sequencing of a large number of genomic regions on a single platform. Because the method uses commonly available reagents it can be developed further by a community of users.
Stress-related problems in silicon technology (1991)

The silicon integrated-circuits chip is built by contiguously embedding, butting, and overlaying structural elements of a large variety of materials of different elastic and thermal properties. Stress develops in the thermal cycling of the chip. Furthermore, many structural elements such as CVD (chemical vapor deposition) silicon nitride, silicon dioxide, polycrystalline silicon, etc., by virtue of their formation processes, exhibit intrinsic stresses. Large localized stresses are induced in the silicon substrate near the edges and corners of such structural elements. Oxidation of nonplanar silicon surfaces produces another kind of stress that can be very damaging, especially at low oxidation temperatures. Mismatch of atomic sizes between dopants and the silicon, and heteroepitaxy produce another class of strain that can lead to the formation of misfit dislocations. Here we review the achievements to date in understanding and modeling these diverse stress problems.
Inhibitors of cell division reversibly modify hemoglobin concentration in human erythroleukemia K562 cells (1981)

The human leukemia K562 cell line can be induced by 20 micro M hemin to reversibly accumulate embryonic and fetal hemoglobins without any change in the rate of cell division. When we reduced the rate of cell division by glutamine starvation or addition of hydroxyurea, the cells increased by tenfold the basal hemoglobin level of 0.3–0.5 pg Hb/cell. The combined effects of hemin and inhibitors of cell division permitted K562 cells to attain levels of hemoglobin (26–34 pg Hb/cell) close to that found in normal red cells. This superinduction was reversible and cells could be recycled indefinitely. Furthermore, electrofocusing experiments show that the three primary hemoglobin species produced by these cells (Hb Gower 1, Hb Portland, and fetal Hb), were induced, or reinduced, synchronously by inhibitors of cell division but asynchronously by hemin. Differing effects of hemin and inhibitors of cell division were observed in the absence of irreversible differentiation and suggest different molecular mechanisms controlling globin gene expression.
Bone Marrow–Derived Mesenchymal Stem Cells Transduced With Scleraxis Improve Rotator Cuff Healing in a Rat Model (2011)

Biologic augmentation of acutely injured rotator cuffs with Scx-transduced MSCs may improve rotator cuff tendon healing and reduce the incidence of re-tears. However, further studies are needed to determine if this remains safe and effective in larger models.
Stabilizing or Destabilizing Oligodeoxynucleotide Duplexes Containing Single 2′‐Deoxyuridine Residues with 5‐Alkynyl Substituents (2004)

The 5-position of pyrimidines in DNA duplexes offers a site for introducing alkynyl substituents that protrude into the major groove and thus do not sterically interfere with helix formation. Substituents introduced at the 5-position of the deoxyuridine residue of dU:dA base pairs may stabilize duplexes and reinforce helices weakened by a low G/C content, which would otherwise lead to false negative results in DNA chip experiments. Here we report on a method for preparing oligonucleotides with a 5-alkynyl substituent at a 2'-deoxyuridine residue by on-support Sonogashira coupling involving the fully assembled oligonucleotide. A total of 25 oligonucleotides with 5-alkynyl substituents were prepared. The substituents either decrease the UV melting point of the duplex with the complementary strand or increase it by up to 7.1 degrees C, compared with that of the unmodified control duplex. The most duplex-stabilizing substituent, a pyrenylbutyramidopropyne moiety, is likely to intercalate but does not prevent sequence-specific base pairing of the modified deoxyuridine residue or the neighboring nucleotides. It also increases the signal for a target strand when employed on a small oligonucleotide microarray. The ability to tune the melting point of a DNA dodecamer duplex with a single side chain over a temperature range of >11 degrees C may prove useful when developing DNA sequences for biomedical applications.
Intraoperative systemic lidocaine inhibits the expression of HMGB1 in patients undergoing radical hysterectomy. (2014)

Surgery stressors trigger inflammatory response and excessive inflammatory response leads to organ failure or even septic shock. HMGB1 as a later inflammatory cytokines and a critical mediator of severe sepsis is always associated with the aggravation of organ failure. Previous study shows that lidocaine can inhibit the expression of HMGB1 in macrophage of septic rats and protect animals from organ failure. The present study sought to determine whether intraoperative systemic lidocaine could attenuate the level of HMGB1 by inhibiting it expression in PBMC from patients underwent radical hysterectomy. Thirty patients were recruited and divided randomly into two groups according to the difference of study medicine. Patients in lidocaine group received an intravenous bolus infusion of 1.5 mg/kg of lidocaine followed by a continuous infusion of 1.5 mg/kg/h till discharged from operating room, and those in the control group received normal saline. Peripheral blood sample was drawn at pre-surgery, discharge from operating room and 48 h post-surgery. Monocytes were isolated and cultured with medium alone or with LPS. HMGB1 protein in serum or in supernatant of PBMC was detected with ELISA, while the HMGB1 mRNA in PBMC was determined by real-time quantitative PCR. The result showed that lidocaine not only attenuated the level of HMGB1 protein in serum and supernatant, but inhibited the transcription of HMGB1 mRAN in PBMC. The present study of us demonstrated that intraoperative systemic lidocaine can attenuate the level of HMGB1 and inhibit its expression in PBMC from patients underwent radical hysterectomy. Therefore, lidocaine may play an important role in many other clinical diseases by inhibiting HMGB1.
Structure and aggregation in dilate solution of surface active agents (1953)

Summary Critical micelle concentrations (CMC) are shown to depend on chain length. All straight chain saturated surface active agents of equal ion length have approximately the same CMC. Thus a C 13 fatty acid soap, a C 12 sulfonate, a C 11 sulfate, and a C 12 ammonium chloride have CMC values of 0.010–0.014M. Values of CMC are not changed to any extent by substitution near the hydrophilic head of one, two, or three groups, even as large as hydroxyethyl, in place of the amine hydrogens in the cationic detergents. However substitution with dihydroxypropyl groups has a marked effect on association in C 12 but not in the C 16 series, indicating that the relative lengths of the two chains must be considered as an important factor in association. This is well illustrated in the dialkylsulfosuccinate series, and in a tetradecane sulfate series in which the −SO 4 Na group was progressively moved down the chain, particularly when the branched chain compounds are compared with the corresponding straight chain detergents of length equal to the maximum length from the charged head to the ultimate carbon atom. Introduction of double bonds causes a small but definite increase in CMC whereas polar substitution in the chain results in a marked increase in CMC. Possible micelle structures are discussed in the light of these association phenomena, and it is concluded that the assignment of a definite size and shape to micelles appears at the present time to be slightly premature. However if one includes the concept of relative order‐disorder in the micelle as one of the factors, in addition to chain length, type of detergent, and environment, which are important in micelle structure, it is possible to explain partially the apparent marked differences which have been reported for micelles of different surface active agents.
SQuAD: 100,000+ Questions for Machine Comprehension of Text (2016)

We present the Stanford Question Answering Dataset (SQuAD), a new reading comprehension dataset consisting of 100,000+ questions posed by crowdworkers on a set of Wikipedia articles, where the answer to each question is a segment of text from the corresponding reading passage. We analyze the dataset to understand the types of reasoning required to answer the questions, leaning heavily on dependency and constituency trees. We build a strong logistic regression model, which achieves an F1 score of 51.0%, a significant improvement over a simple baseline (20%). However, human performance (86.8%) is much higher, indicating that the dataset presents a good challenge problem for future research. The dataset is freely available at https://stanford-qa.com
Neurosteroid Analogues. 17. Inverted Binding Orientations of Androsterone Enantiomers at the Steroid Potentiation Site on γ-Aminobutyric Acid Type A Receptors (2011)

The enantiomer pair androsterone and ent-androsterone are positive allosteric modulators of γ-aminobutyric acid (GABA) type A receptors. Each enantiomer was shown to bind at the same receptor site. Binding orientations of the enantiomers at this site were deduced using enantiomer pairs containing OBn substituents at either C-7 or C-11. 11β-OBn-substituted steroids and 7α-OBn-substituted ent-steroids potently displace [(35)S]-tert-butylbicyclophosphorothionate, augment GABA currents, and anesthetize tadpoles. In contrast, 7β-OBn-substituted steroids and 11α-OBn-substituted ent-steroids have diminished actions. The results suggest that the binding orientations of the active analogues are inverted relative to each other with the 7α- and 11β-substituents similarly located on the edges of the molecules not in contact with the receptor surface. Analogue potentiation of the GABA current was abrogated by an α(1) subunit Q241L mutation, indicating that the active analogues act at the same sites in α(1)β(2)γ(2L) receptors previously associated with positive neurosteroid modulation.
Fibroblast growth factor andex vivoexpansion of hematopoietic progenitor cells (2004)

Fibroblast growth factor (FGF) belongs to a family of heparin-binding polypeptides and shows multiple functions including cell proliferation, differentiation, survival and motility. The expression of FGF receptors is widely distributed on different hematopoietic progenitor cells and stromal cells, and FGFs play an important role in hematopoietic stem cell homeostasis. FGFs have been shown to sustain the proliferation of hematopoietic progenitor cells, maintaining their primitive phenotype. Basic FGF (bFGF, FGF-2) stimulates the formation of an adherent stromal cell layer in human long-term bone marrow cultures, and promotes hematopoietic cell development. FGF-2 has also been shown to synergize with other hematopoietic growth factors to enhance in vitro colony formation by several classes of hematopoietic progenitor cells. Results of ex vivo expansion and clinical trials to date suggest that hematopoietic cells cultured under stroma-free cytokine combination conditions may be insufficient to restore hematopoiesis after a myeloablative conditioning regimen, although some recent trials demonstrated an improvement in engraftment and a reduction of the period of pancytopenia, especially neutrophils and platelets, after transplantation. A recent study by our group demonstrated that FGF-2 is effective in supporting the generation of megakaryocytic progenitor cells during ex vivo expansion. These observations could be useful in reducing the long period of severe thrombocytopenia that occurs frequently after umbilical/placental cord blood transplantation. The development of more effective amplifying systems for hematopoietic stem/progenitor cells can be expected since FGFs have multiple functions in hematopoiesis.
Full Nonlinear Conversion of Broadband Frequency Combs generated by Four-Wave Mixing in Highly Nonlinear Fibers (2009)

We generate a 200-nm optical frequency comb at 1.5 microns by injecting two single-frequency lasers into a highly nonlinear fiber, and explore its spectral phase properties and high power to demonstrate full nonlinear conversion into its second harmonic. Combs of optical frequencies with 100-nm (~ 48 THz) bandwidths, centered at 790-800 nm and spaced by 0.8-1 nm (380-470 GHz) were produced by second harmonic and multiple sum frequency generation simply by focusing into a 2-mm long nonlinear crystal. Conventional birefringence phase matching was used in normal incidence configuration without tilting the crystal.
Endoderm and Pancreatic Islet Lineage Differentiation from Human Embryonic Stem Cells (2006)

Human embryonic stem cells (HESCs) are a potential source of insulin-producing tissue for transplantation. Recent studies have begun to define factors that promote definitive endoderm formation from HESCs, but conditions permitting complete islet specification in vitro have not been described. Here, we study spontaneous differentiation of HESCs to definitive endoderm and pancreatic progenitor cells, and begin to determine which aspects of the protocol are required for this cell fate commitment. HESCs were differentiated in culture for up to 10 weeks, including an embryoid body (EB) formation step. Modifications to the protocol included elimination of the EB phase, varying initial cell cluster size when forming EBs, and addition of mesoderm-derived cells to EBs. Differentiated cells were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. HESCs are capable of spontaneous differentiation to cells expressing the definitive endoderm and pancreatic progenitor markers Foxa2, Sox17, and Pdx1, and ultimately, some cells express islet endocrine hormones. This differentiation occurs to a much greater extent when an EB formation step is included. Increased expression of endoderm markers during and after EB formation also correlated strongly with the size of cell clusters used to start EBs, as well as the addition of mesoderm- derived embryonic cells. This study demonstrates that a subset of differentiated HESC progeny adopt an endoderm fate and exhibit the capacity for further pancreatic lineage specification in vitro. Basal conditions were established for examining factors that can commit HESC-derived endoderm cells to specific pancreatic lineages.
Overexpression of Kinesins Mediates Docetaxel Resistance in Breast Cancer Cells (2009)

Resistance to chemotherapy remains a major barrier to the successful treatment of cancer. To understand mechanisms underlying docetaxel resistance in breast cancer, we used an insertional mutagenesis strategy to identify proteins whose overexpression confers resistance. A strong promoter was inserted approximately randomly into the genomes of tumor-derived breast cancer cells, using a novel lentiviral vector. We isolated a docetaxel-resistant clone in which the level of the kinesin KIFC3 was elevated. When KIFC3 or the additional kinesins KIFC1, KIF1A, or KIF5A were overexpressed in the breast cancer cell lines MDA-MB231 and MDA-MB 468, the cells became more resistant to docetaxel. The binding of kinesins to microtubules opposes the stabilizing effect of docetaxel that prevents cytokinesis and leads to apoptosis. Our finding that kinesins can mediate docetaxel resistance might lead to novel therapeutic approaches in which kinesin inhibitors are paired with taxanes.
Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors (1996)

The insulin-like growth factors (IGFs), IGF-I and IGF-II, comprise a conserved pair of secreted proteins with diverse effects on growth, development, and metabolism. Insulin-like growth factor action is initiated upon binding to cell-surface receptors and is modulated through interactions with secreted IGF binding proteins (IGFBPs). The last decade has seen an explosion of new information about the physiological roles of the IGFs. In this review, we critically examine this information from biochemical, cell biological, and molecular genetic perspectives. We discuss the structures and functions of the two IGF receptors, outline the actions of the six IGFBPs, and summarize and interpret recent studies highlighting essential roles for components of the IGF system in the growth and development of the embryo and fetus, in tissue differentiation, in cell survival and proliferation, and in cancer. These results are discussed in the context of new opportunities for understanding the mechanisms of IGF action in multiple biological processes.
Primer extension technique for the detection of single nucleotide in genomic DNA (1990)

Journal Article Primer extension technique for the detection of single nucleotide in genomic DNA Get access Boris P. Sokolov Boris P. Sokolov Institute of Medical GeneticsMoskvorechie St 1, Moscow, 115478, USSR Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 12, 25 June 1990, Page 3671, https://doi.org/10.1093/nar/18.12.3671 Published: 25 June 1990 Article history Received: 20 December 1989 Published: 25 June 1990
Dendritic cells are critical accessory cells for thymus-dependent antibody responses in mouse and in man. (1983)

We report that dendritic cells (DC) are necessary and potent accessory cells for anti-sheep erythrocyte responses in both mouse and man. In mice, a small number of DC (0.3-1% of the culture) restores the response of B/T-lymphocyte mixtures to that observed in unfractionated spleen. An even lower dose (0.03-0.1% DC) is needed if the T cells have been primed to antigen. Responses are both antigen and T cell dependent. Selective depletion of DC from unfractionated spleen with the monoclonal antibody 33D1 and complement ablates the antibody response. In contrast to DC, purified spleen macrophages are weak or inactive stimulators. However, when mixed with DC, macrophages can increase the yield of antibody-secreting cells about 2-fold. In man, small numbers (0.3-1%) of blood DC stimulate antibody formation in vitro. Purified human monocytes do not stimulate but in low doses (1% of the culture) inhibit the antibody response. Likewise, selective removal of human monocytes with antibody and complement enhances or accelerates the development of antibody-secreting cells. We conclude that DC are required for the development of T-dependent antibody responses by mouse and human lymphocytes in vitro.