gebhart/patrepeval huggingface dataset:
Model for assessment of carious lesion remineralization, and remineralization by a novel toothpaste. (1999)

This study is of a novel toothpaste which induced remineralization of carious lesions in specific pathogen-free Osborne-Mendel rats. Randomly distributed weanlings in 7 groups (n = 10) each were initially induced to develop carious lesions as a result of a severe dietary and bacteriological challenge. Thus, all were inoculated with S. mutans 10449S, ate diet 2000CS (containing 56% cornstarch) ad libitum, and, upon weaning and for 10 additional days, drank demineralized water supplemented to 10% (w/v) with sucrose (SW) ad libitum. During these 10 days, 6 of the 7 groups of rats were topically treated with a slurried F(-)-free placebo toothpaste. On the 10th day after initial inoculation, two groups were sacrificed, one which had been treated with the placebo and the one which had been untreated. The remaining groups were then provided unsupplemented demineralized water (DW), fed diet 2000CS, and topically treated with either of 5 coded toothpastes: a slurry of the F(-)-free placebo, a similar slurry of a conventional sodium fluoride toothpaste (Crest Regular) containing about 383 ppm F-, or one of three prototype toothpastes formulated by Enamelon, Inc. containing soluble calcium and phosphate salts. Two of these contained 377 ppm F- after mixing their components, either as sodium monofluorophosphate (E-MFP) or as NaF (E-NaF). The third prototype contained 0 ppm F- (E-w/o F). Test items were applied to the dentition for one minute/day, five days/week. These 5 remaining groups were sacrificed 13 days after the DW provision. After defleshing, heads were coded randomly and scored blindly for carious lesions. The exchange of DW for SW was associated with highly significant reductions of 10449S recoveries (p < 0.001), but there were no differences in recoveries among the groups as a function of toothpaste type. Total mandibular and maxillary sulcal and smooth surface caries scores were statistically significantly lower for the E-NaF-treated group at 23 days than for the 23-day placebo-, E-w/o F(-)-, and conventional NaF toothpaste-treated group. Reductions were most impressive quantitatively on approximal tooth surfaces, where both the E-MFP and E-NaF groups had the lowest scores, but were also statistically significant at sulcal surfaces for the E-NaF group. Thus, this study model can be used to detect significant remineralization effects, as occurred with the prototype toothpaste E-NaF.
Totalsynthese eines Neobetanidin‐Derivates und des Neobetenamins (1970)

Abstract The total synthesis of a neobetanidine derivative ( 3b ) is described. Preliminary experiments led to the synthesis of neobetenamine ( 4 ), which presents the ring system of neobetanidine ( 3 ). A general method for the synthesis of several compounds containing the essential neobetanidine chromophore (a 1, 7‐diazaheptamethine system incorporating a pyridine ring) consisted of Vilsmeier ‐ Haack condensations involving the active (enolizable) methyl group of γ‐picoline. Neobetenamine ( 4 ) resulted from this reaction with N‐formyl‐indoline, and also by an amine exchange between indoline and the Vilsmeier ‐ Haack product from γ‐picoline and N‐methyl‐formanilide. The methyl group of γ‐picoline‐2, 6‐dicarboxylic ester 9 , however, was resistant to the Vilsmeier ‐ Haack condensation, but could be activated by introduction of a carboxyl into it: 4‐chloropyridine‐2, 6‐dicarboxylic ester ( 11a ) (from chelidamic ester) was used to alkylate malonic ester. The product ( 12a ) lost only one carboxyl group when saponified. The resulting 2, 6‐dicarboxy‐pyridine‐4‐acetic acid ( 13a ) readily underwent a novel decarboxylative condensation with the Meerwein acetal of dimethyl formamide to 4‐(2‐dimethylamino‐vinyl)‐2, 6‐dimethoxycarbonyl‐pyridine ( 14b ), the first synthetic derivative of a neobetalaine. The enamine 14b was subjected to amine exchange reactions with indoline to 2‐decarboxy‐5, 6‐dideoxy‐neobetanidine dimethyl ester ( 15 ), and with ( S )‐cyclodopa ( 16 ) 5, 6‐di‐O‐methyl‐neobetanidine trimethyl ester ( 3b ). The latter was identical with the diazomethane transformation product of betanidine ( 1 ), the aglucone of the pigment of the red beet, betanine. A few proton resonance and electron spectral properties, as well as the basicities of several of the synthesized compounds, are tabulated and discussed as far as they express special structural and electronic features of the common 1, 7‐diazaheptamethine chromophore.
Pharmacological and immunohistochemical characterization of the APJ receptor and its endogenous ligand apelin (2003)

Apelin peptides have recently been identified to be the endogenous ligands for the G protein-coupled receptor APJ. However, little is known about the physiological roles of this ligand-receptor pairing. In the present study we investigated the pharmacology of several apelin analogues at the human recombinant APJ receptor using radioligand binding and functional assays. This has led to the identification of key residues in the apelin peptide required for functional potency and binding affinity through structure-activity studies. In particular, we have identified that replacement of leucine in position 5, or arginine in position 2 and 4 of the C-terminal apelin peptide, apelin-13, resulted in significant changes in pharmacology. We also investigated the detailed localization of pre-proapelin and APJ receptor mRNA in a wide range of human, rat and mouse tissues using quantitative RT-PCR, and carried out a detailed immunohistochemical study of the distribution of the APJ receptor in rat brain and spinal cord. Interestingly, the APJ receptor was not only co-localized in white matter with GFAP in the spinal cord, but was also clearly localized on neurones in the brain, suggesting that this receptor and its peptide may be involved in a wide range of biological process yet to be determined.
Correlation of Maternal Antibody Deficiency with Susceptibility to Neonatal Group B Streptococcal Infection (1976)

We investigated the role of maternal antibody in neonatal Group B streptococcal infection with a radioactive antigen-binding assay employing a purified polysaccharide antigen with both Type III and Group B determinants. Serums from seven women who gave birth to infants who had invasive Group B streptococcal infection with Type III strains were all deficient in antibody. In contrast, serums from 22 of 29 pregnant Type III vaginal carriers whose infants were healthy contained antibody with a prevalence significantly different from that in women delivering infants with Type III disease (P less than 0.01). Three healthy neonates born to women with antibody in serums had demonstrable antibody in umbilical-cord serum. These data suggest that transplacental transfer of maternal antibody protects infants from invasive Group B streptococcal infection with Type III strains.
A threonine residue in the seventh transmembrane domain of the human A1 adenosine receptor mediates specific agonist binding. (1994)

The A1 adenosine receptor is a member of the seven-transmembrane G protein-coupled, receptor superfamily. This receptor binds the purine nucleoside adenosine with high affinity and inhibits the activity of adenylate cyclase. We have used site-directed mutagenesis and functional expression studies to examine the role of the threonine residue, located at position 277 in transmembrane domain VII of the human A1 receptor. Mutation of Thr-277 to either serine or alanine resulted in the expression of receptors that had essentially no change in binding affinity for the A1 selective antagonist 8-cyclo-pentyl-1,3-dipropylxanthine. Mutation of Thr-277 to serine resulted in modest (4.4-8.6-fold) but significant increases in the observed Ki values for three adenosine agonists, namely N-(1-methyl-2-phenethyl)adenosine (R-PIA or S-PIA) and 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-beta-L- ribofuranuronamide) (NECA). However, mutation of Thr-277 to alanine resulted in no significant changes in the Ki for R-PIA or S-PIA but did result in a highly significant 437-fold increase in the Ki for NECA. This demonstrates that the hydroxyl moiety of Thr-277 mediates agonist but not antagonist binding and, more specifically, that this residue forms a probable molecular contact site with the 5' substitution found in NECA.
Feed development for fed‐batch CHO production process by semisteady state analysis (2009)

Semisteady state cultures are useful for studying cell physiology and facilitating media development. Two semisteady states with a viable cell density of 5.5 million cells/mL were obtained in CHO cell cultures and compared with a fed-batch mode control. In the first semisteady state, the culture was maintained at 5 mM glucose and 0.5 mM glutamine. The second condition had threefold higher concentrations of both nutrients, which led to a 10% increase in lactate production, a 78% increase in ammonia production, and a 30% reduction in cell growth rate. The differences between the two semisteady states indicate that maintaining relatively low levels of glucose and glutamine can reduce the production of lactate and ammonia. Specific amino acid production and consumption indicated further metabolic differences between the two semisteady states and fed-batch mode. The results from this experiment shed light in the feeding strategy for a fed-batch process and feed medium enhancement. The fed-batch process utilizes a feeding strategy whereby the feed added was based on glucose levels in the bioreactor. To evaluate if a fixed feed strategy would improve robustness and process consistency, two alternative feeding strategies were implemented. A constant volume feed of 30% or 40% of the initial culture volume fed over the course of cell culture was evaluated. The results indicate that a constant volumetric-based feed can be more beneficial than a glucose-based feeding strategy. This study demonstrated the applicability of analyzing CHO cultures in semisteady state for feed enhancement and continuous process improvement.
Electromagnetic field investigation on different cancer cell lines (2014)

There is a strong interest in the investigation of extremely low frequency Electromagnetic Fields (EMF) in the clinic. While evidence about anticancer effects exists, the mechanism explaining this effect is still unknown. We investigated in vitro, and with computer simulation, the influence of a 50 Hz EMF on three cancer cell lines: breast cancer MDA-MB-231, and colon cancer SW-480 and HCT-116. After 24 h preincubation, cells were exposed to 50 Hz extremely low frequency (ELF) radiofrequency EMF using in vitro exposure systems for 24 and 72 h. A computer reaction-diffusion model with the net rate of cell proliferation and effect of EMF in time was developed. The fitting procedure for estimation of the computer model parameters was implemented. Experimental results clearly showed disintegration of cells treated with a 50 Hz EMF, compared to untreated control cells. A large percentage of treated cells resulted in increased early apoptosis after 24 h and 72 h, compared to the controls. Computer model have shown good comparison with experimental data. Using EMF at specific frequencies may represent a new approach in controlling the growth of cancer cells, while computer modelling could be used to predict such effects and make optimisation for complex experimental design. Further studies are required before testing this approach in humans.
Taiwanese Triads in the Transnational Imagination (2004)

Gina Marchetti argues that Edward Yang's Mahjong and Hou Hsiaohsien's Good-Bye South, Good-Bye plays off the Taiwanese gangster culture against the international youth subcultures in order to negotiate national identity.
Molecular Flexibility Profiling Using NMR Spectroscopy (1999)

Molecular flexibility is a factor that is not extensively studied in most pharmaceutical research efforts. When it is, the level of effort is high involving the preparation of detailed models supported by either molecular dynamics simulations and/or Nuclear Magnetic Resonance data. While these studies are both powerful and illuminating, they cannot be routinely applied in a drug discovery setting as they are time and expertise intensive. Yet there seems to be little doubt that at least in some cases, molecular flexibility plays a key role in complex formation. A simple, rapid and generally applicable flexibility profiling protocol was applied to two model systems and data describing the internal mobility of carbon atoms were obtained. The protocol utilizes the Model Free approach and NMR data to characterize the internal molecular dynamics of these compounds. The first model system consisted of fluorene and diphenylmethane where the anticipated flexibility trends were observed in the data providing a link between chemical intuition and the experimental results. Data on a second model system, which consisted of two Paclitaxel analogs, showed predictable patterns including dynamical phenyl and methyl groups and a relatively immobile taxane core. Subtle differences in the internal dynamics within the taxane core suggest that it cannot be considered as a rigid structure. Key advantages of using this approach are that no prior knowledge or supposition of dynamical features is required, the protocol can be carried out in most medicinal chemistry laboratories and the data obtained provide a common, empirically derived reference point to discuss the effects of molecular flexibility on activity.
The Notch ligands DLL1 and JAG2 act synergistically to regulate hair cell development in the mammalian inner ear (2005)

The mammalian auditory sensory epithelium, the organ of Corti, contains sensory hair cells and nonsensory supporting cells arranged in a highly patterned mosaic. Notch-mediated lateral inhibition is the proposed mechanism for creating this sensory mosaic. Previous work has shown that mice lacking the Notch ligand JAG2 differentiate supernumerary hair cells in the cochlea, consistent with the lateral inhibitory model. However, it was not clear why only relatively modest increases in hair cell production were observed in Jag2 mutant mice. Here, we show that another Notch ligand, DLL1, functions synergistically with JAG2 in regulating hair cell differentiation in the cochlea. We also show by conditional inactivation that these ligands probably signal through the NOTCH1 receptor. Supernumerary hair cells in Dll1/Jag2 double mutants arise primarily through a switch in cell fate, rather than through excess proliferation. Although these results demonstrate an important role for Notch-mediated lateral inhibition during cochlear hair cell patterning, we also detected abnormally prolonged cellular proliferation that preferentially affected supporting cells in the organ of Corti. Our results demonstrate that the Notch pathway plays a dual role in regulating cellular differentiation and patterning in the cochlea, acting both through lateral inhibition and the control of cellular proliferation.
Nonparametric Belief Propagation and Facial Appearance Estimation (2002)

In many applications of graphical models arising in computer vision, the hidden variables of interest are most naturally specified by continuous, non-Gaussian distributions. There exist inference algorithms for discrete approximations to these continuous distributions, but for the high-dimensional variables typically of interest, discrete inference becomes infeasible. Stochastic methods such as particle filters provide an appealing alternative. However, existing techniques fail to exploit the rich structure of the graphical models describing many vision problems. Drawing on ideas from regularized particle filters and belief propagation (BP), this paper develops a nonparametric belief propagation (NBP) algorithm applicable to general graphs. Each NBP iteration uses an efficient sampling procedure to update kernel-based approximations to the true, continuous likelihoods. The algorithm can accomodate an extremely broad class of potential functions, including nonparametric representations. Thus, NBP extends particle filtering methods to the more general vision problems that graphical models can describe. We apply the NBP algorithm to infer component interrelationships in a parts-based face model, allowing location and reconstruction of occluded features.
Superantigen antagonist blocks Th1 cytokine gene induction and lethal shock (2001)

Bacterial superantigens trigger an excessive, Th1-cytokine response leading to toxic shock. We designed a peptide antagonist that inhibits SEB-induced expression of human genes for IL-2, IFN-gamma, and TNF-beta, cytokines that mediate shock. The peptide antagonist shows homology to a beta-strand-hinge-alpha-helix domain that is conserved structurally in superantigens produced by Staphylococcus aureus and Streptococcus pyogenes yet remote from known binding sites for the major histocompatibility class II molecule and T-cell receptor. For Th1-cell activation, superantigens depend on this domain. The peptide protected mice against lethal challenge with SEB or SEA. Moreover, it rescued mice undergoing toxic shock. Surviving mice rapidly developed broad-spectrum, protective immunity, which rendered them resistant to further lethal challenges with different staphylococcal and streptococcal superantigens. Thus, the lethal effect of superantigens, mediated by Th1 cytokines, can be blocked with a peptide antagonist that inhibits their action at the top of the toxicity cascade, before activation of T cells takes place.
Ductal Carcinoma In Situ Biology, Biomarkers, and Diagnosis (2017)

Ductal carcinoma <i>in situ</i> (DCIS) is an often-diagnosed breast disease and a known, non-obligate, precursor to invasive breast carcinoma. In this review, we explore the clinical and pathological features of DCIS, fundamental elements of DCIS biology including gene expression and genetic events, the relationship of DCIS with recurrence and invasive breast cancer, and the interaction of DCIS with the microenvironment. We also survey how these various elements are being used to solve the clinical conundrum of how to optimally treat a disease that has potential to progress, and yet is also likely over-treated in a significant proportion of cases.
Clinical evaluation of the Serum CrossLaps One Step ELISA, a new assay measuring the serum concentration of bone-derived degradation products of type I collagen C-telopeptides (1998)

The Serum CrossLaps One Step ELISA is a sandwich assay using two monoclonal antibodies specific for a beta-aspartate form of the epitope EKAHDGGR derived from the carboxy-terminal telopeptide region of type I collagen alpha1-chain. Our objective was to assess the clinical value of the Serum CrossLaps assay for monitoring antiresorptive therapy in osteoporosis treatment. Samples obtained from postmenopausal women treated with different doses of cyclic or continuous hormone replacement therapy (HRT) with an estrogen analog (tibolone) or with a bisphosphonate (ibandronate) were measured in the Serum CrossLaps One Step ELISA at baseline and at various time points during therapy. The corresponding urine samples were measured in the urine CrossLaps ELISA and corrected for creatinine excretion. The serum CrossLaps measurements and corresponding urinary CrossLaps measurements were highly correlated (r >0.8 for all studies). The serum and urine CrossLaps measurements showed a significant decrease among the women treated with clinically relevant doses of either of the antiresorptive agents. Furthermore, the annual percentage change in bone mineral density (BMD) correlated with the measured changes in CrossLaps concentration. The serum CrossLaps assay showed a specificity of 83-100% and a sensitivity of 59-83% for assessing BMD changes. The corresponding values for the creatinine-corrected urinary measurements were 83-92% specificity and 68-79% sensitivity. We conclude that performance of the convenient Serum CrossLaps One Step ELISA is at least equivalent to that of the urine text for follow up of antiresorptive treatment in osteoporosis. Further studies are needed to optimize its use in this and other clinical applications.
Antigen-Driven Oligoclonal Expansion of Tumor-Infiltrating B Cells in Infiltrating Ductal Carcinoma of the Breast (2002)

The objective of this study was to determine whether tumor-infiltrating B cells (TIL-B) of infiltrating ductal carcinoma (IDC) of the breast represent a tumor-specific humoral immune response. Immunohistochemical analysis of three Her-2/neu-negative IDC tumors from geriatric patients showed that TIL-B cluster in structures similar to germinal centers containing CD20(+) B lymphocyte and CD3(+) T lymphocyte zones with interdigitating CD21(+) follicular dendritic cells, suggesting an in situ immune response. A total of 29, 31, and 58 IgG1 H chain clones was sequenced from the three IDC tumors, respectively. Intratumoral oligoclonal expansion of TIL-B was demonstrated by a preponderance (45-68%) of clonal B cells. In contrast, only 7% of tumor-draining lymph node and 0% of healthy donor PBL IgG H chains were clonal, consistent with the larger repertoires of node and peripheral populations. Patterns and levels of TIL-B IgG H chain somatic hypermutation suggested affinity maturation in intratumoral germinal centers. To examine the specificity of TIL-B Ig, a phage-displayed Fab library was generated from the TIL-B of one IDC tumor. Panning with an allogeneic breast cancer cell line enriched Fab binding to breast cancer cells, but not nonmalignant cell lines tested. However, panning with autologous tumor tissue lysate increased binding of Fab to both tumor tissue lysate and healthy breast tissue lysate. These data suggest an in situ Ag-driven oligoclonal B cell response to a variety of tumor- and breast-associated Ags.
Triplex-Forming Oligonucleotides and Their Use in the Analysis of Gene Transcription (2003)

The ability of oligonucleotides to bind double-stranded DNA in a sequence specific manner, forming a DNA triple helix structure, has led to a number of novel approaches in the study of various structural and functional properties of DNA in vitro and in vivo including transcription inhibition (1–3), site-directed mutagenesis (4) and detection of DNA polymorphism (5).
The Pathogenesis of Sepsis (2011)

Sepsis is a serious clinical condition that represents a patient's response to a severe infection and has a very high mortality rate. Normal immune and physiologic responses eradicate pathogens, and the pathophysiology of sepsis is due to the inappropriate regulation of these normal reactions. In an ideal scenario, the first pathogen contact with the inflammatory system should eliminate the microbe and quickly return the host to homeostasis. The septic response may accelerate due to continued activation of neutrophils and macrophages/monocytes. Upregulation of lymphocyte costimulatory molecules and rapid lymphocyte apoptosis, delayed apoptosis of neutrophils, and enhanced necrosis of cells/tissues also contribute to the pathogenesis of sepsis. The coagulation system is closely tied to the inflammatory response, with cross talk between the two systems driving the dysregulated response. Biomarkers may be used to help diagnose patients with sepsis, and they may also help to identify patients who would benefit from immunomodulatory therapies.