gebhart/patrepeval huggingface dataset:
Use of [3H]Triphenylmethylphosphomum Cation for Estimating Membrane Potential in Neuroblastoma Cells (1984)

The lipophilic permeant cation [3H]triphenylmethylphosphonium (TPMP) was used to estimate membrane potential in neuroblastoma N1E 115 cells under carefully controlled conditions. The cation distributes into the cells only in the presence of a lipophilic anion, and tetraphenylboron and picrate have been used for this purpose. The potassium salt of tetraphenylboron is poorly soluble, so that studies in high [K+] media are difficult with this anion whereas picrate, at the concentrations required, hyperpolarises the cells. The effect of muscarinic receptor activation was investigated by treating cells with carbachol but no effect was seen either on [3H] TPMP distribution or electrophysiological parameters. The use of [3H]TPMP for qualitative and quantitative evaluation of membrane potential in these cells is discussed.
Requirement of rapid Ca2+ entry and synaptic activation of metabotropic glutamate receptors for the induction of long‐term depression in adult rat hippocampus (1998)

1. During block of gamma-aminobutyric acid-A-mediated inhibition, low-frequency stimulation (2 Hz, 900 pulses) to Schaffer collateral-CA1 neuron synapses of adult rat hippocampus induced an N-methyl-D-aspartate receptor-independent, postsynaptic Ca2+-dependent depression of synaptic strength (long-term depression; LTD). 2. Ratio imaging with fura-2 revealed moderate dendritic [Ca2+] increases (approximately 500 nM) during only the initial approximately 30 s of the 7.5 min stimulation period. Conditioning for 30 s was, however, insufficient to induce LTD. 3. The [Ca2+] changes were insensitive to the metabotropic glutamate receptor (mGluR) antagonist (+)-alpha-methyl-4-carboxyphenylglycine (MCPG). MCPG, however, completely blocked LTD when present during conditioning. 4. The [Ca2+] changes were abolished by postsynaptic hyperpolarization (-110 mV at the soma). Hyperpolarizing neurons to -110 mV during conditioning significantly attenuated LTD induction. 5. LTD induction was also blocked by the postsynaptic presence of the protein kinase C inhibitor peptide PKC(19-36). 6. These results suggest that LTD induction in adult hippocampus by prolonged low-frequency stimulation depends on both a rapid Ca2+ influx through voltage-sensitive channels and synaptic stimulation of mGluRs which may be coupled to phospholipase C.
Characterization of a monoclonal antibody-defined human melanoma-associated antigen susceptible to induction by immune interferon. (1987)

To develop monoclonal antibodies (mAb) recognizing human melanoma-associated antigens (MAA) susceptible to modulation by immune interferon (IFN-gamma), hybridomas were constructed with splenocytes from a BALB/c mouse immunized with IFN-gamma-treated melanoma cells Colo 38. Screening of supernatants with control and IFN-gamma-treated melanoma cells showed that the mAb CL203 and CL207 display preferential reactivity with IFN-gamma-treated melanoma cells. The two mAb recognize the same (or spatially close) determinant on a 96,000 MAA which has a density of 0.36 X 10(6) antigenic sites/cell on untreated melanoma cells Colo 38 and of 1.39 X 10(6) and 1.54 X 10(6) on melanoma cells Colo 38 treated with IFN-gamma (final concentration, 200 U/ml) for 24 and 48 hr, respectively. The effect of IFN-gamma on the 96,000 MAA is dose- and time-dependent, reversible, and blocked by inhibitors of RNA and protein synthesis. Furthermore, the effect of IFN-gamma on the induction of the 96,000 MAA appears to be specific, inasmuch as IFN-alpha and IFN-beta do not induce the expression of the 96,000 MAA. The latter is also induced by IFN-gamma in a variety of carcinoma cell lines, but its level is markedly lower than on melanoma cells. Furthermore, the apparent m.w. of the antigen synthesized by the carcinoma cell lines in the presence of IFN-gamma ranges between 93,000 and 96,000. This molecular heterogeneity appears to reflect differences in the degree of glycosylation of the polypeptide moiety because the antigen synthesized by a variety of cell lines in the presence of tunicamycin has an apparent m.w. of 51,000.
Non-equilibrium imbibition of a porous block (1996)

We consider a phenomenological model proposed by Barenblatt [1] for non-equilibrium two-phase flow in porous media. In the case of zero total flow it reduces to a pair of equations: where Φ(σ) is a non-decreasing (not necessarily increasing) smooth function defined in the interval 0 ≤ σ ≤ 1. We consider initial-boundary problems for this system in which the initial data are given only for s, and the boundary data only for ς (which corresponds to the physical sense of the model). The degenerate character of the system allows us to apply simple topological methods. We show that the boundary problem is well-posed, in the sense that there exits a unique (weak) solution which satisfies the maximum principle and depends continuously on the initial data. The solution is no less smooth than the initial and boundary data.
Modulation of bcl-2 and p27 in human primitive proliferating hematopoietic progenitors by autocrine TGF-β1 is a cell cycle–independent effect and influences their hematopoietic potential (2000)

Primitive, proliferating hematopoietic progenitors (defined as cytokine low-responding primitive progenitors; CLRPP), isolated from human CD34+ cells, expressed endoglin (CD105) and produced transforming growth factor-beta1 (TGF-beta1). Culture of CLRPP in serum-free conditions with anti-TGF-beta1 monoclonal antibody produced a substantial decrease in bcl-2 protein/RNA levels and a significant reduction of cloning and long-term culture-initiating cell (LTC-IC) activities. GATA-1 and PU.1 RNA levels were significantly up-regulated in anti-TGF-beta1-treated CLRPP, which generated an increased number of cells expressing CD15/CD11b/glycophorin-A. The described effects of TGF-beta1 neutralization were observed in the absence of any relevant effect on cell cycle; number of cell divisions; p53, c-myc, and p21 RNA levels; bcl-xL and bax protein levels; and c-myc/p16/p21/p107/Rb cell cycle-related protein levels. A relevant increase in p27 protein levels was observed in anti-TGF-beta1-treated CLRPP, suggesting a role for p27 in the regulation of the hematopoietic potential. The present study on human progenitors and previously reported data on TGF-beta1 knockout mice suggest that, at the autocrine level, the cell cycle inhibitor TGF-beta1 plays an important role in regulating the survival and differentiation of primitive proliferating hematopoietic progenitors by cell cycle-independent mechanisms.
Cell-Intrinsic NF-κB Activation Is Critical for the Development of Natural Regulatory T Cells in Mice (2011)

Our results indicate that Treg cell-intrinsic NF-κB activation is essential for thymic Treg cell differentiation, and further suggest pharmacological NF-κB inhibition as a potential therapeutic approach for manipulating this process.
Parameter Estimation in Large Dynamic Paired Comparison Experiments (1999)

SUMMARY Paired comparison data in which the abilities or merits of the objects being compared may be changing over time can be modelled as a non-linear state space model. When the population of objects being compared is large, likelihood-based analyses can be too computationally cumbersome to carry out regularly. This presents a problem for rating populations of chess players and other large groups which often consist of tens of thousands of competitors. This problem is overcome through a computationally simple non-iterative algorithm for fitting a particular dynamic paired comparison model. The algorithm, which improves over the commonly used algorithm of Elo by incorporating the variability in parameter estimates, can be performed regularly even for large populations of competitors. The method is evaluated on simulated data and is applied to ranking the best chess players of all time, and to ranking the top current tennis-players.
Discovery of (R,E)-N-(7-Chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a Novel, Potent, and WT Sparing Covalent Inhibitor of Oncogenic (L858R, ex19del) and Resistant (T790M) EGFR Mutants for the Treatment of EGFR Mutant Non-Small-Cell Lung Cancers (2016)

Over the past decade, first and second generation EGFR inhibitors have significantly improved outcomes for lung cancer patients with activating mutations in EGFR. However, both resistance through a secondary T790M mutation at the gatekeeper residue and dose-limiting toxicities from wild-type (WT) EGFR inhibition ultimately limit the full potential of these therapies to control mutant EGFR-driven tumors and new therapies are urgently needed. Herein, we describe our approach toward the discovery of 47 (EGF816, nazartinib), a novel, covalent mutant-selective EGFR inhibitor with equipotent activity on both oncogenic and T790M-resistant EGFR mutations. Through molecular docking studies we converted a mutant-selective high-throughput screening hit (7) into a number of targeted covalent EGFR inhibitors with equipotent activity across mutants EGFR and good WT-EGFR selectivity. We used an abbreviated in vivo efficacy study for prioritizing compounds with good tolerability and efficacy that ultimately led to the selection of 47 as the clinical candidate.
Pathways regulating lens induction in the mouse (2004)

For more than a century, the lens has provided a relatively simple structure in which to study developmental mechanisms. Lens induction, where adjacent tissues signal the cell fate changes that result in lens formation, have been of particular interest. Embryological manipulations advancing our understanding have included the Spemann optic rudiment ablation experiments, optic vesicle transplantations as well as more contemporary work employing lineage tracers. All this has revealed that lens induction signaling is a multi-stage process involving multiple tissue interactions. More recently, molecular genetic techniques have been applied to an analysis of lens induction. This has led to the identification of signaling pathways required for lens induction and early lens development. These include the bone morphogenetic protein (Bmp) signaling pathways where Bmp4 and Bmp7 have been implicated. Though no fibroblast growth factor (Fgf) ligand has been implicated at present, the Fgf signaling pathway clearly has an important role. A series of transcription factors involved in early lens development have also been identified. These include Pax6, the Meis transcription factors, Six3, Mab21l1, FoxE3, Prox1 and Sox2. Importantly, analysis has indicated how these elements of the lens induction pathway are related and has defined genetic models to describe the process. It is a future challenge to test existing genetic models and to extend them to incorporate the tissue interactions mediated by the molecules involved. Given the complexity of this and many other developmental processes, a second century of analysis will be welcome.
GFAP and S100B in the acute phase of mild traumatic brain injury (2012)

A relation between GFAP with imaging studies and outcome (determined by RTW) was found in contrast to S100B. As the positive predictive value of GFAP is limited in this category of TBI patients, this biomarker is not suitable for prediction of individual patient outcome.
Radiation‐induced loss of cell surface CD47 enhances immune‐mediated clearance of human papillomavirus‐positive cancer (2013)

The increasing incidence of human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (OSSC) demands development of novel therapies. Despite presenting at a more advanced stage, HPV(+) oropharyngeal squamous cell carcinoma (OSCC) have a better prognosis than their HPV(-) counterparts. We have previously demonstrated that clearance of HPV(+) OSCC during treatment with radiation and chemotherapy requires an immune response which is likely responsible for the improved clinical outcomes. To further elucidate the mechanism of immune-mediated clearance, we asked whether radiation therapy induces tumor cell changes that allow the body to recognize and aid in tumor clearance. Here, we describe a radiation-induced change in tumor surface protein expression that is critical for immune-mediated clearance. Radiation therapy decreases surface expression of CD47, a self-marker. CD47 is frequently overexpressed in head and neck squamous cell carcinoma and radiation induces a decrease of CD47 in a dose-dependent manner. We show that both in vitro and in vivo tumor cell CD47 protein levels are restored over time after sublethal radiation exposure and that protein levels on adjacent, normal tissues remain unaffected. Furthermore, reduction of tumor cell CD47 increases phagocytosis of these cells by dendritic cells and leads to increased interferon gamma and granzyme production from mixed lymphocytes. Finally, decreasing tumor cell CD47 in combination with standard radiation and chemotherapy results in improved immune-mediated tumor clearance in vivo. These findings help define an important mechanism of radiation-related immune clearance and suggest that decreasing CD47 specifically on tumor cells may be a good therapeutic target for HPV related disease.
Group BStreptococcusCapsular Polysaccharide-Cholera Toxin B Subunit Conjugate Vaccines Prepared by Different Methods for Intranasal Immunization (2001)

Group B Streptococcus (GBS) type III capsular polysaccharide (CPS III) was conjugated to recombinant cholera toxin B subunit (rCTB) using three different methods which employed (i) cystamine and N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP), (ii) carbodiimide with adipic acid dihydrazide (ADH) as a spacer, or (iii) reductive amination (RA). The CPS III-rCTB conjugates were divided into large- and small-molecular-weight (M(r)) fractions, and the immunogenicities of the different preparations after intranasal (i.n.) immunization were studied in mice. Both large- and small-M(r) conjugates of CPS III-rCTB(RA) or CPS III-rCTB(ADH) induced high, almost comparable levels of CPS-specific immunoglobulin G (IgG) in serum, lungs, and vagina that were generally superior to those obtained with CPS III-rCTB(SPDP) conjugates or a CPS III and rCTB mixture. However, the smaller-M(r) conjugates of CPS III-rCTB(RA) or CPS III-rCTB(ADH) in most cases elicited a lower anti-CPS IgA immune response than the large-M(r) conjugates, and the highest anti-CPS IgA titers in both tissues and serum were obtained with the large-M(r) CPS III-rCTB(RA) conjugate. Serum IgG anti-CPS titers induced by the CPS III-rCTB(RA) conjugate had high levels of specific IgG1, IgG2a, IgG2b, and IgG3 antibodies. Based on the effectiveness of RA for coupling CPS III to rCTB, RA was also tested for conjugating GBS CPS Ia with rCTB. As for the CPS III-rCTB conjugates, the immunogenicity of CPS Ia was greatly increased by conjugation to rCTB. Intranasal immunization with a combination of CPS Ia-rCTB and CPS III-rCTB conjugates was shown to induce anti-CPS Ia and III immune responses in serum and lungs that were fully comparable with the responses to immunization with the monovalent CPS Ia-rCTB or CPS III-rCTB conjugates. These results suggest that the GBS CPS III-rCTB and CPS Ia-rCTB conjugates prepared by the RA method may be used in bivalent and possibly also in multivalent mucosal GBS conjugate vaccines.
HRCT findings in the lungs of primary care patients with lower respiratory tract infection (2002)

Purpose: To survey the prevalence and type of lung patterns detectable at high-resolution CT (HRCT) in a primary care population seeking help for cough and fever. Material and Methods: The HRCT patterns of 103 patients obtained at the primary visit to a municipal health centre for cough and fever were evaluated. Forced expiratory examinations were obtained in 93 patients. Results: Lower respiratory tract infection (LRTI)-related findings (present at inclusion, healed at follow-up, not explained by any other factor) were seen in 19 patients (18.7%), of whom 11 also showed opacities, even though of lesser extent, at conventional chest radiography. The following patterns were found: ground-glass opacity (58%), discrete consolidations (52%), confluent consolidations (16%; 1 case with an air bronchogram), air space nodules (10%), peribronchovascular thickening (37%), tree-in-bud pattern (26%), free pleural fluid (5%), and septal thickening (5%). An expiratory mosaic pattern was seen in 19 (20%) out of 93 patients. In addition, lymph node enlargement (&amp;gt;1 cm) was recorded in 7 patients out of 103. Conclusion: HRCT is more sensitive than chest radiography in detecting LRTI-related lung lesions in a primary care population. The pattern typically comprises subtle scattered polymorphous opacities with varying attenuation affecting several lung segments. LRTI-related HRCT pattern deserves consideration as a differential diagnostic alternative in patients examined due to any lower respiratory tract symptoms.
Estimating the Contribution of Lead-Based Paint to Soil Lead, Dust Lead, and Childhood Blood Lead (1995)

Young children are particularly susceptible to lead carried in fine particles of surface soil (exterior dust) and in household dust. Multi-media environmental and biological samples may allow causal inferences about the relative importance of different sources and pathways in childhood lead exposure, and about the effectiveness of intervention strategies. Methods include: (1) statistical inferences about pathways using structural equation modeling; (2) inferences about pathways using physical tracers of sources; (3) inferences based on mass balance estimates. Structural equation modeling allows estimation of both direct and indirect exposures to lead-based paint. For example, chips of exterior lead-based paint may be ingested directly, may contribute to surface soil lead which is ingested, and may also be transported into household dust which is ingested. It is often possible to identify soil and dust exposure from elevated lead levels on the child's hands. We use structural equation models in cross-sectional field studies in some Western communities, to demonstrate the role of lead paint as a source of lead exposure. Stronger causal inferences about sources and pathways can be made when there are physical identifiers of the source, such as an unusual ratio of some stable lead isotopes. Another approach is to carry out an intervention, such as removal or encapsulation of the lead-based paint, or removal of the contaminated soil and dust associated with the paint. If lead-based paint is not removed and there is some recontamination of these media over time after the intervention, then we can attribute the exposure to lead paint.
Using the Internet. (1994)

As wide-area computer networks grow in size, so too are they developing simple tools which can be used to send and receive vast amounts of information easily and efficiently. And even though primary and secondary schools are not as yet using these networks extensively, there is every indication that they will do so in the near future. This paper outlines some of the basic access, database, and search tools available on the worlds largest computer network, the Internet. A list of reference books, manuals, and on-line electronic papers about the Internet is included.
Fungal colonization of the paranasal sinuses* (1999)

Fungal infection of the paranasal sinuses occur in four primary types: acute invasive (1), chronic invasive (2), chronic fungus ball (3) and allergic fungal sinusitis (4). The first and second form can be fatal and is often found in immunosuppressed patients. The present paper concerns a group of immunocompetent patients with non-invasive chronic sinusitis caused by moulds. Over the period from 1994 to 1998, 132 tissue samples from the paranasal sinuses obtained by endoscopic operation from 117 patients was examined for mycotic infections. The mycological examination was carried out if granulomatous and crumbly material was seen in the sinus by endoscopy (91 times maxillary sinus, 23 times ethmoid sinus, 11 times frontal sinus, 7 times sphenoid sinus). Out of 117 patients 29 were positive (24,9%). From 132 surgical specimens fungi were proved in 34 times (25,7%). The following fungal species were isolated: Aspergillus fumigatus 17 times, other Aspergillus spp 6 times, Alternaria alternate 2, Penicillium rugulosum 1, and moulds without differentiation 5 times. In the histological examination an invasive mycelial growth in the mucous membrane or in the bones was never observable. Our findings represented a commensal colonization of the paranasal sinuses, but not a mycosis. The colonization is evidently assisted by a chronic hyperthrophic sinusitis with increased mucus production which impedes the mucociliary clearance. For immunosuppressed patients, however, this situation causes a danger of invasion with fatal consequences.
Complement receptor is an inhibitor of the complement cascade. (1981)

A glycoprotein from the membrane of human erythrocytes has been identified as a receptor for C3b (CR1). It promotes the dissociation of the alternative pathway C3 convertase C3b,Bb and the cleavage of C3b by C3b/C4b inactivator. We find that CR1 also inactivates the C3 and C5 convertases of the classical pathway. CR1 inhibits the consumption of C3 by C3 convertase EAC142 and enhances the decay of C4b,2a sites. On a weight basis, CR1 is approximately 5-10 times more active than C4 binding protein, a serum inhibitor of C4b,2a. The binding of 125I-CR1 to EAC14 cells is inhibited by C2. Therefore, it is likely that CR1 and C2 compete for a site on C4b. CR1 inhibited C5 convertase even more effectively, but had no effect on the assembly of the late complement components. At high concentrations, CR1 alone has no irreversible effects on cell-bound C4b. In the fluid phase, CR1 can function as a cofactor for the cleavage of the alpha' chain of C4b by C3b/C4b inactivator. A well-known function of CR1 is to promote adherence of microbes or immune complexes bearing C3b and C4b to cells. This interaction could result in a microenvironment damaging to the plasma membrane of the responding cell because the extrinsic C3b and C4b fragments can serve as additional sites of assembly of enzymes of the cascade. We therefore wish to propose that CR1 on the surface of cells supplies an increased local concentration of a strong inhibitor of the amplifying enzymes of the complement system and provides cells with a mechanism for circumventing damage when they bind C3b- and C4b-bearing substrates.
An Atlas of Human Gametes and Conceptuses (1999)

Foreword Preface Acknowledgements A REVIEW OF HUMAN GAMETES AND CONCEPTUSES Gamete Maturation The Human Oocyte The Human Spermatozoon The Sperm-Penetrated Human Oocyte The Cleaving Human Preembryo Preembryo Grading and Degree of Cytoplasmic Fragmentation Preembryos with the Ability to Implant Abnormal Morphology of the Human Oocyte and Conceptus Cryopreservation Assisted Fertilization by Intracytoplasmic Sperm Injection (ICSI) Assisted Hatching and Fragment Removal Preimplantation Genetic Diagnosis (PGD) Epilogue Appendix HUMAN GAMETES AND CONCEPTUSES ILLUSTRATED Index. ISBN: 1-85070-016-8 216 pages (Hardback) Color illustrated 98-26503 Published: April 1999 $149.95 / GBP100
Introduction to X-ray powder diffractometry (1997)

Characteristics of X-Radiation. The Crystalline State. Diffraction Theory. Sources for the Generation of X-Radiation. Detectors and Detection Electronics. Production of Monochromatic Radiation. Instruments for the Measurement of Powder Patterns. Alignment and Maintenance of Powder Diffractometers. Specimen Preparation. Acquisition of Diffraction Data. Reduction of Data from Automated Powder Diffractometers. Qualitative Analysis. Quantitative Analysis. Appendices. Index.