gebhart/patrepeval huggingface dataset:
Force Titrations and Ionization State Sensitive Imaging of Functional Groups in Aqueous Solutions by Chemical Force Microscopy (1997)

Chemical force microscopy (CFM) was used to probe interactions between ionizable and neutral functional groups in aqueous solutions. Force microscope probe tips and sample substrates have been covalently modified with self-assembled monolayers (SAMs) terminating in distinct functional groups. SAMs were prepared by treating Au-coated or uncoated tips and substrates with functionalized thiols or silanes, respectively. A force microscope has been used to characterize adhesive and frictional interactions between probe tips and substrates modified with SAMs that terminate in −NH2, −COOH, −OH, and −CH3 functional groups as a function of solution pH and ionic strength. In general, adhesion and friction forces were observed to depend on the chemical identity of the tip and sample surface and also were found to be highly sensitive to the changes in the ionization state of the terminal functionalities induced by varying the solution pH. Adhesion measurements made as a function of pH (force titrations) on amine-terminated surfaces exhibit a sharp decrease in the adhesion force at pH values below 4.5. The pKa estimated from this drop in adhesion, which is due to the protonation of amine groups on the sample and tip, 3.9, is similar to the value determined by conventional contact angle wetting studies of these same surfaces. The large decrease in the pK of the amine group relative to homogeneous solution was attributed to the relatively hydrophobic environment of the amine group in these SAMs. Adhesion measurements made as a function of pH on −COOH-terminated surfaces exhibited a large drop in adhesion force for pH values greater than 5. The pKa estimated from these data, 5.5, is similar to the free aqueous solution value. In addition, the adhesion force between nonionizable −OH and −CH3 groups was found to be independent of solution pH. The measured adhesive forces were interpreted using a contact mechanics model that incorporated the effects of the double layer free energy. Analyses of repulsive electrostatic forces and adhesion data recorded as a function of ionic strength were used to determine properties of the double layer. The pH dependence of the friction force between tips and samples modified with SAMs terminating in −COOH, −OH, and −CH3 groups was measured as a function of applied load. For a given pH, these data exhibit a linear dependence on load with the slope corresponding to the coefficient of friction. The coefficient of friction for −OH and −CH3 groups was independent of pH, while the friction coefficient for −COOH-terminated surfaces drops significantly at a pH corresponding to the pKa determined by adhesion measurements. The pH-dependent changes in friction forces for ionizable groups were exploited to map spatially changes in ionization state on surfaces terminating in −COOH and −OH functional groups.
The effects of fluoride concentration and the level of cariogenic challenge on caries development in desalivated rats (1998)

Dental caries is an infectious and transmissible disease that continues to affect the majority of people. The presence of carbohydrate, mainly sucrose in the diet, is an important factor in its occurrence. The amount of fluoride required for optimal protective effect where there is a high caries challenge is unclear. Differences in the intensity of cariogenic challenge, for whatever reason, may play a part in determining fluctuations in the effectiveness of fluoride. The purpose of this study was to evaluate the effect of different concentrations of fluoride on the development of caries and explore the cariostatic effect of fluoride under various levels of cariogenic challenge. The study comprises two experiments. In experiment I, 60 desalivated Sprague Dawley rats infected with Streptococcus sobrinus were offered the following to drink for 21 days: group (1), sterile distilled water (SDW); (2) 10 parts/10(6) F SDW; (3) 20 parts/10(6) F SDW; (4) 30 parts/10(6) F SDW; (5) 40 parts/10(6) F SDW. In experiment II, eight groups of 9 rats were placed in a König Höfer programmed feeder and were exposed to different levels of cariogenic challenge through varying frequency of eating and offered water containing 10 parts/10(6) F. In experiment I, exposure to 20, 30 and 40 parts/10(6) F reduced caries development significantly: fluoride, at 10 parts/10(6), reduced the severity of the carious lesions. In this model of severe cariogenic challenge, the results suggest that elevated concentrations of fluoride might be effective in patients at high caries risk. In experiment II, fluoride reduced the incidence and severity of smooth-surface caries in all groups. The protective effect of fluoride decreased as the number of exposures to sugar increased. It is concluded that the effectiveness of fluoride is influenced by the level of cariogenic challenge and that consideration should be given to adjusting the level of fluoride exposure based on perceived caries risk, and that there is a maximum therapeutic effect of fluoride beyond which no additional protection can be expected.
Stereospecific Synthesis, Structural Characterisation and Resolution of 2‐Phospha[3]ferrocenophane Derivatives – a New Chiral Scaffold (2007)

Abstract The first 2‐phospha[3]ferrocenophanes containing stereogenic carbon atoms in the three‐atom bridge have been synthesised from phenylphosphane by stereospecific ring‐closing phosphanation reactions. Either α‐substituted 1,1′‐bis(hydroxymethyl)ferrocenes or the corresponding 2‐oxa‐[3]ferrocenophanes have been used as diastereomerically pure starting materials. The resolution of 1,2,3‐triphenyl[2]phosphaferrocenophane has been achieved by chromatographic separation of the diastereomeric adducts of a chiral cyclopalladate complex. The X‐ray crystal structures of two 2‐phospha[3]ferrocenophane‐borane complexes are also reported. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)
The FlhD/FlhC complex, a transcriptional activator of the Escherichia coli flagellar class II operons (1994)

The Escherichia coli flhD operon encodes two genes, flhD and flhC. Both gene products were overproduced and purified. The purified proteins formed a complex consisting of two FlhD and two FlhC molecules. Mobility shift assays showed that the FlhD/FlhC complex had a DNA-binding activity and bound to the upstream regions of fliA, flhB, and fliL operons (class II), which are under direct control of the flhD operon. DNase I footprinting analyses of FlhD/FlhC binding to the three class II promoter regions revealed protection of a 48-bp region of the fliA operon between positions -41 to -88, a 50-bp region of the flhB operon between positions -28 to -77, and a 48-bp region of the fliL operon between positions -29 to -76. In vitro transcription experiments demonstrated that the FlhD/FlhC complex is a transcriptional activator required for the transcription of the three class II operons examined in vitro.
Mucosal immunogenicity of polysaccharides conjugated to a peptide or multiple-antigen peptide containing T- and B-cell epitopes (1995)

In this study we investigated the mucosal and systemic responses to two T-cell-independent polysaccharides, a serogroup f polysaccharide (formed of rhamnose glucose polymers [RGPs]) from Streptococcus mutans OMZ 175 and a mannan from Saccharomyces cerevisiae, covalently conjugated either to a linear peptide (peptide 3) or to a multiple-antigen peptide (MAP), both derived from S. mutans protein SR, an adhesin of the I/II protein antigen family of oral streptococci. Peptide 3 and MAP, which contained at least one B- and one T-cell epitope, were tested as carriers for the polysaccharides and as protective immunogens. Intragastric intubation of rats with the conjugates (RGPs-peptide 3, RGPs-MAP, mannan-peptide 3, and mannan-MAP) associated with liposomes produced salivary immunoglobulin A (IgA) antibodies which reacted with RGPs or mannan, peptide 3 or MAP, protein SR, and S. mutans or S. cerevisiae cells. Administration of conjugate boosters to the animals showed that both carriers conjugated to the polysaccharides were able to induce, in immunized animals, a salivary antipolysaccharide IgA memory. In contrast, animals primed and challenged with unconjugated polysaccharide showed no anamnestic response. Rats orally immunized with the conjugates also developed systemic primary antipolysaccharide and antipeptide IgM antibody responses which were characterized by a switch from IgM to IgG during the course of the secondary response. Data presented here demonstrated that both peptide 3 and the MAP construct can act as good carriers for orally administered polysaccharides. Unexpectedly, the use of a MAP did not further improve the immunogenicity of polysaccharides at the mucosal level; nevertheless, such a construct should be of great interest in overcoming the problem of genetic restriction induced by linear peptides.
Specific Binding of ApoA-I, Enhanced Cholesterol Efflux, and Altered Plasma Membrane Morphology in Cells Expressing ABC1 (2000)

Mutations of the ABC1 transporter have been identified as the defect in Tangier disease, characterized by low HDL and cholesterol ester accumulation in macrophages. A full-length mouse ABC1 cDNA was used to investigate the mechanisms of lipid efflux to apoA-I or HDL in transfected 293 cells. ABC1 expression markedly increased cellular cholesterol and phospholipid efflux to apoA-I but had only minor effects on lipid efflux to HDL. The increased lipid efflux appears to involve a direct interaction between apoA-I and ABC1, because ABC1 expression substantially increased apoA-I binding at the cell surface, and chemical cross-linking and immunoprecipitation analysis showed that apoA-I binds directly to ABC1. In contrast to scavenger receptor BI (SR-BI), another cell surface molecule capable of facilitating cholesterol efflux, ABC1 preferentially bound lipid-free apoA-I but not HDL. Immunofluorescence confocal microscopy showed that ABC1 is primarily localized on the cell surface. In the absence of apoA-I, cells overexpressing ABC1 displayed a distinctive morphology, characterized by plasma membrane protrusions and resembling echinocytes that form when there are excess lipids in the outer membrane hemileaflet. The studies provide evidence for a direct interaction between ABC1 and apoA-I, but not HDL, indicating that free apoA-I is the metabolic substrate for ABC1. Plasma membrane ABC1 may act as a phospholipid/cholesterol flippase, providing lipid to bound apoA-I, or to the outer membrane hemileaflet.
Design, synthesis and in vitro testing of methotrexate carrier conjugates linked via oligopeptide spacers. (1995)

A range of methotrexate (MTX)-spacer-human serum albumin (HSA) conjugates have been prepared. They have been designed to release one of the following materials: MTX, MTX-Lys (alpha-epsilon) or MTX-Lys (gamma-epsilon). These materials have previously been shown to be the low-molecular-weight products released on hydrolysis of a MTX-HSA conjugate by rat liver tritosomes. Preliminary studies were carried out using a lysine residue, linked by the epsilon-amino group to the oligopeptide chain, as a model for the polymer. This use of this model system indicated that an Ala-Leu-Ala-Leu spacer was cleaved by lysosomal enzymes with release of the appropriate derivative. Analysis of the lysosomal digestion products of the MTX-spacer-HSA conjugates showed that the model system appeared to work well. A maximum rate of release of 100% MTX-Lys (alpha-epsilon) from a MTX-spacer-HSA within 48 h was obtained, as compared to 5% in 48 h obtained for MTX-HSA. Determination of the in vitro cytotoxicity of the conjugates showed that release of 'free' MTX was 10-fold more cytotoxic than either of the MTX-Lys derivatives, but the level of release of MTX from MTX-HSA was 10-fold less than that of the MTX-Lys materials.
Heparan sulfate proteoglycans of the cardiovascular system. Specific structures emerge but how is synthesis regulated? (1997)

2-O -sulfated glucuronic acid; GlcNAc, N -acetylglucosamine; GlcN(Ac/S), N -acetyl
Rabbit Ig kappa 1b6 gene structure. (1990)

Previous studies employing Southern blot analyses have detected multiple kappa-homologous sequences within EcoRI-digested DNA isolated from kappa 1b6 homozygous rabbits and kappa 1b6 L chain secreting RMH H158 cell line. These results are very unexpected because the published partial protein sequence for the kappa 1b6 C region is incompatible with an EcoRI restriction endonuclease recognition sequence at the nucleotide level for this allotype. To determine their identity, the kappa-homologous sequences were isolated from DNA extracted from a kappa 1b6 L chain secreting RMH H158 cell line by molecular cloning. Structural analyses demonstrated these sequences to contain genetic information encoding the majority of the kappa 1b6 L chain gene locus. The protein sequence deduced from the kappa 1b6 C region gene was shown to differ from the published partial kappa 1b6 C region protein sequence at five amino acid positions. One of these differences results in a glycine to serine interchange that introduces an EcoRI restriction endonuclease recognition site within the kappa 1b6 C region gene. Subsequent genomic Southern blot analyses confirmed this structural assignment. Based on these data, the EcoRI-sensitive kappa-homologous fragments present within the genomes of the RMH H158 cell line and kappa 1b6 homozygous rabbits represent the nominal kappa 1 gene and not an alternative kappa isotype or kappa pseudogene. Rabbit Ig kappa 1 allelic nucleotide sequence homology comparisons have shown the isolated kappa 1b6 J-C gene locus to display common structural features previously identified in other kappa 1 alleles.
[(HL)2Fe6(NCMe)m]n+ (m = 0, 2, 4, 6; n = −1, 0, 1, 2, 3, 4, 6): An Electron-Transfer Series Featuring Octahedral Fe6 Clusters Supported by a Hexaamide Ligand Platform (2011)

Using a trinucleating hexaamide ligand platform, the all-ferrous hexanuclear cluster ((H)L)(2)Fe(6) (1) is obtained from reaction of 3 equiv of Fe(2)(Mes)(4) (Mes = 2,4,6-Me(3)C(6)H(2)) with 2 equiv of the ligand ((H)L)H(6). Compound 1 was characterized by X-ray diffraction analysis, (57)Fe Mössbauer, SQUID magnetometry, mass spectrometry, and combustion analysis, providing evidence for an S=6 ground state and delocalized electronic structure. The cyclic voltammogram of [((H)L)(2)Fe(6)](n+) in acetonitrile reveals a rich redox chemistry, featuring five fully reversible redox events that span six oxidation states ([((H)L)(2)Fe(6)](n+), where n=-1→4) within a 1.3 V potential range. Accordingly, each of these species is readily accessed chemically to provide the electron-transfer series [((H)L)(2)Fe(6)(NCMe)(m)][PF(6)](n) (m=0, n=-1 (2); m=2, n=1 (3); m=4, n=2 (4); m=6, n=3 (5); m=6, n=4 (6)). Compounds 2-6 were isolated and characterized by X-ray diffraction, (57)Fe Mössbauer and multinuclear NMR spectroscopy, and combustion analysis. Two-electron oxidation of the tetracationic cluster in 6 by 2 equiv of [NO](+) generates the thermally unstable hexacationic cluster [((H)L)(2)Fe(6)(NCMe)(m)](6+), which is characterized by NMR and (57)Fe Mössbauer spectroscopy. Importantly, several stepwise systematic metrical changes accompany oxidation state changes to the [Fe(6)] core, namely trans ligation of solvent molecules and variation in Mössbauer spectra, spin ground state, and intracluster Fe-Fe separation. The observed metrical changes are rationalized by considering a qualitative, delocalized molecular orbital description, which provides a set of frontier orbitals populated by Fe 3d electrons.
Trellis termination in CPM (2000)

A technique is presented for terminating the encoder of continuous phase modulation (CPM) into a known trellis state. This is useful when block-wise a posteriori probability processing is employed, e.g. in iterative (‘turbo’) receivers for serially concatenated CPM.
Expansion of Myeloid Suppressor Cells in SHIP-Deficient Mice Represses Allogeneic T Cell Responses (2004)

Previously we demonstrated that SHIP(-/-) mice accept allogeneic bone marrow transplants (BMT) without significant acute graft-vs-host disease (GvHD). In this study we show that SHIP(-/-) splenocytes and lymph node cells are poor stimulators of allogeneic T cell responses that cause GvHD. Intriguingly, SHIP(-/-) splenocytes prime naive T cell responses to peptide epitopes, but, conversely, are partially impaired for priming T cell responses to whole Ag. However, dendritic cells (DC) purified from SHIP(-/-) splenocytes prime T cell responses to allogeneic targets, peptide epitopes, and whole Ag as effectively as SHIP(+/+) DC. These findings point to an extrinsic effect on SHIP(-/-) DC that impairs priming of allogeneic T cell responses. Consistent with this extrinsic effect, we found that a dramatic expansion of myeloid suppressor cells in SHIP(-/-) mice impairs priming of allogeneic T cells. These findings suggest that SHIP expression or its activity could be targeted to selectively compromise T cell responses that mediate GvHD and graft rejection.
Influence of carbon incorporation on dopant surface segregation in molecular-beam epitaxial growth of silicon (2000)

We describe the effect of carbon incorporation into Si on dopant surface segregation during molecular-beam epitaxial growth. Low concentration of carbon can significantly reduce the surface segregation of boron and phosphorus. Combining the surface diffusion model with a two-state exchange process, we are able to model the experimental results over the whole temperature range between 350 and 800 °C. Each exchange process alone is not sufficient to describe surface segregation at all investigated temperatures. Our results show that the presence of carbon lowers the energy difference for boron in subsurface and surface states. The energy barriers for surface diffusion as well as for the two-state exchange process are not affected by carbon.
Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Glucose Production via the Hepatic Sympathetic Innervation in Rats (2010)

This study demonstrates that PACAP-38 signaling via sympathetic preautonomic neurons located in the paraventricular nucleus is an important component in the hypothalamic control of hepatic glucose production.
Coordination Chemistry of a Modular N,C-Chelating Oxazole-Carbene Ligand and Its Applications in Hydrosilylation Catalysis (2006)

Reaction of 1-mesitylimidazole with 2-chlorobenzoxazole gave the 2-benzoxazolyl imidazolium salt bzoxcarbH+Cl- (1), which was converted to the silver N-heterocyclic carbene complex [AgI(bzoxcarb)Cl] (2) by reaction with Ag2O in dichloromethane. The crystal structure analysis confirmed the monomeric nature of complex 2. The silver complex 2 was reacted with [PdCl2(COD)] to yield the corresponding palladium complex [PdCl2(bzoxcarb)] (3), for which an X-ray diffraction study established a distorted square planar configuration with the imidazolyl and the oxazolyl ring lying within the molecular plane. Upon direct reaction of the imidazolium salt 1 with Pd(OAc)2/NaI, a bis-carbene palladium complex [PdI2(bzoxcarb)2] (4) was obtained. The rhodium complex [RhCl(bzoxcarb)(CO)] (5) was prepared in high yield in a one-step reaction of 1 with [Rh(acac)(CO)2] (acac = acetylacetonate). The silver N-heterocyclic carbene complex 2 was also used as carbene transfer reagent in the synthesis of the platinum complex [PtCl2(bzoxcarb)] (6), which was found to be an active catalyst for the hydrosilylation of alkenes and alkynes.
Synthesis of(E)7‐[[2‐[4‐(m‐trifluoromethylphenoxy)‐3α and 3β‐hydroxy‐1‐butenyl]‐5‐oxo‐1 ‐pyrrolidinyl]]heptanoic acids (1983)

Abstract The synthesis of an 8‐aza‐PGE 1 analog, ( E )‐7‐[[2‐[4‐( m ‐trifluoromethylphenoxy)‐3α and 3β‐hydroxy‐1‐butenyl]‐5‐oxo‐pyrrolidinyl]]heptanoic acids is reported.
Antibody targeting of the EphA2 tyrosine kinase inhibits malignant cell behavior. (2002)

EphA2 is a transmembrane receptor tyrosine kinase that is up-regulated on many aggressive carcinoma cells. Despite its overexpression, the EphA2 on malignant cells fails to bind its ligand, ephrinA1, which is anchored to the membrane of adjacent cells. Unlike other receptor kinases, EphA2 demonstrates kinase activity that is independent of ligand binding. However, ligand binding causes EphA2 to negatively regulate tumor cell growth and migration. Herein, we translate knowledge of EphA2 into strategies that selectively target malignant cells. Using a novel approach to preserve extracellular epitopes and optimize antibody diversity, we generated monoclonal antibodies that identify epitopes on the extracellular domain of EphA2. EphA2 antibodies were selected for their abilities to inhibit behaviors that are unique to metastatic cells while minimizing damage to nontransformed cells. A subset of EphA2 monoclonal antibodies were found to inhibit the soft agar colonization by MDA-MB-231 breast tumor cells but did not affect monolayer growth by nontransformed MCF-10A breast epithelial cells. These EphA2 antibodies also prevented tumor cells from forming tubular networks on reconstituted basement membranes, which is a sensitive indicator of metastatic character. Biochemical analyses showed that biologically active antibodies induced EphA2 phosphorylation and subsequent degradation. Antisense-based targeting of EphA2 similarly inhibited soft agar colonization, suggesting that the antibodies repress malignant behavior by down-regulating EphA2. These results suggest an opportunity for antibody-based targeting of the many cancers that overexpress EphA2. Our studies also emphasize how tumor-specific cellular behaviors can be exploited to identify and screen potential therapeutic targets.
Megestrol Acetate in Patients with AIDS and Cachexia (1994)

Objective: To study the effects of a megestrol acetate liquid formulation (800 mg/d) on body weight, body composition, caloric intake, and mental outlook in patients with the acquired immunodeficiency syndrome (AIDS) who had cachexia. Design: Twelve-week, multicenter, randomized, double-blind, placebo-controlled trial. Setting: Multiple clinical centers. Patients: 100 patients with AIDS who had weight loss of 10% or more of ideal body weight were randomly assigned to placebo (n = 48) or megestrol acetate (n = 52). Measurements: Caloric intake, body weight, body composition, and sense of well-being. Results: Most patients receiving megestrol acetate had increased caloric intake resulting in body weight gain (mainly fat mass). From baseline to week 8, the megestrol acetate group increased their daily caloric intake by 608 calories, whereas the placebo group increased intake by 134 calories (difference, 474 calories; 95% CI, −68 to 880 calories). Body weight in the megestrol acetate group increased by 3.86 kg from baseline to week 8, although it decreased by 0.46 kg in the placebo group (difference, 4.32 kg; CI, 2.42 to 6.22 kg). At week 8 in the megestrol acetate group, patients gained 3.68 kg in fat mass and those in the placebo group lost 0.28 kg (difference, 3.96 kg; CI, 2.49 to 5.43 kg). Body water, lean mass, and patient survival were not statistically different between treatment groups. Patients treated with megestrol acetate had an increased sense of well-being when compared with patients who received placebo. Conclusions: This megestrol acetate liquid formulation is well tolerated, increases food intake, results in body weight gain, and improves the sense of well-being in cachectic patients with AIDS.
Fatal Anaphylaxis Due to Oral Penicillin (1971)

This fourth reported death from anaphylaxis due to oral penicillin occurred in a 23-year-old postpartum Negro woman with no allergic history after she had taken one 400,000-unit tablet of potassium penicillin G. Autopsy disclosed periorbital and circumoral edema, pulmonary atelectasis, submucosal bronchial edema, bronchial mucous plugs, and visceral congestion. Serum obtained postmortem had moderately strong 7S and 19S IgG hemaggltitinating antibodies to penicillin.