gebhart/patrepeval huggingface dataset:
Regeneration of dentin‐pulp complex with cementum and periodontal ligament formation using dental bud cells in gelatin‐chondroitin‐hyaluronan tri‐copolymer scaffold in swine (2007)

Abstract The purpose of this study is to use a tissue engineering approach for tooth regeneration. The swine dental bud cells (DBCs) were isolated from the developing mandibular teeth, expanded in vitro , and cultured onto cylinder scaffold gelatin‐chrondroitin‐hyaluronan‐tri‐copolymer (GCHT). After culturing in vitro , the DBCs/GCHT scaffold was autografted back into the original alveolar socket. Hematoxylin and eosin (H&amp;E) staining combined with immunohistochemical staining were applied for identification of regenerated tooth structure. After 36‐week post‐transplantation, tooth‐like structures, including well‐organized dentin‐pulp complex, cementum, and periodontal ligament, were evident in situ in two of six experimental animals. The size of the tooth structure (1 × 0.5 × 0.5 cm 3 and 0.5 × 0.5 × 0.5 cm 3 size) appeared to be dictated by the size of the GCHT scaffold (1 × 1 × 1.5 cm 3 ). The third swine was demonstrated with irregular dentin‐bony like calcified tissue about 1 cm in diameter without organized tooth or periodontal ligament formation. The other three swine in the experimental group showed normal bone formation and no tooth regeneration in the transplantation sites. The successful rate of tooth regeneration from DBCs/GCHT scaffolds' was about 33.3%. In the control group, three swine's molar teeth buds were removed without DBCs/GCHT implantation, the other three swine received GCHT scaffold implants without DBCs. After evaluation, no regenerated tooth was found in the transplantation site of the control group. The current results using DBSs/GCHT scaffold autotransplantation suggest a technical breakthrough for tooth regeneration. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
A practical and efficient method for the synthesis of .beta.-lactones (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA practical and efficient method for the synthesis of .beta.-lactonesRick L. Danheiser and James S. NowickCite this: J. Org. Chem. 1991, 56, 3, 1176–1185Publication Date (Print):February 1, 1991Publication History Published online1 May 2002Published inissue 1 February 1991https://pubs.acs.org/doi/10.1021/jo00003a047https://doi.org/10.1021/jo00003a047research-articleACS PublicationsRequest reuse permissionsArticle Views2188Altmetric-Citations95LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Effects of Introducing Silicon Isosteres in COX-2 Inhibitors: A Preliminary In Silico Evaluation (2005)

Since the discovery that the anti-inflammatory effects of cyclooxygenase (prostaglandin endoperoxide H(2) synthetase; COX) inhibitors were dependent on their selectivity for the inducible COX-2 isoform over the constitutive COX-1, many efforts have been devoted towards the design of compounds displaying improved COX-2 selectivity. Classical bioisosteres such as CH-CF and CH(2)-S/O substitutions have been extensively used in the design of the classical COX-2 inhibitors, although silicon isosteres have been so far overlooked. The replacement of a carbon by a silicon atom can have beneficial effects in this particular family of compounds, because the increased bond lengths and altered bond angles brought by the sila-substitution might modify their binding mode to the COX enzymes. In order to evaluate such possible benefits, several well-characterized model inhibitors were selected and docked in the murine COX-2 and COX-1 binding sites. The binding energies for the interaction of each model compound with the respective isoenzymes were derived from the docking data. As in previous publications, these were found to correlate closely (r(2) = 0.66 and 0.75 for COX-2 and COX-1, respectively) with experimental inhibitory activities towards the recombinant enzymes gathered from the literature. These relationships allowed the prediction of the inhibitors activity towards both enzyme isoforms, which further permitted the prediction of their selectivity for COX-2 with an acceptable accuracy (cross-validated squared correlation coefficient q(2) = 0.64). These model compounds were theoretically modified by substituting selected carbon atoms by an sp(3) silicon, and further docked in both COX-2 and COX-1 binding sites in order to derive their predicted inhibitory activity for both isoforms. Except in a few cases, the sila-substitution did not significantly increase the inhibitory activity towards COX-2. In most cases however, it produced a significant decrease in the inhibitory activity towards COX-1. These results indicate that isosteric sila-substitutions could be of value in the design of COX inhibitors with improved selectivity for COX-2.
Priming Immunization with DNA Augments Immunogenicity of Recombinant Adenoviral Vectors for Both HIV-1 Specific Antibody and T-Cell Responses (2010)

ClinicalTrials.gov NCT00102089, NCT00108654.
Conformational Stability of Muscle Acylphosphatase:  The Role of Temperature, Denaturant Concentration, and pH (1998)

The conformational stability (delta G) of muscle acylphosphatase, a small alpha/beta globular protein, has been determined as a function of temperature, urea concentration, and pH. A combination of thermally induced and urea-induced unfolding, monitored by far-UV circular dichroism, was used to define the conformational stability over a wide range of temperature. Through analysis of all these data, the heat capacity change upon unfolding (delta Cp) could be estimated, allowing the determination of the temperature dependence of the main thermodynamic functions (delta G, delta H, delta S). Thermal unfolding in the presence of urea made it possible to extend such thermodynamic analysis to examine these parameters as a function of urea concentration. The results indicate that acylphosphatase is a relatively unstable protein with a delta G(H2O) of 22 +/- 1 kJ mol-1 at pH 7 and 25 degrees C. The midpoints of both thermal and chemical denaturation are also relatively low. Urea denaturation curves over the pH range 2-12 have allowed the pH dependence of delta G to be determined and indicate that the maximum stability of the protein occurs near pH 5.5. While the dependence of delta G on urea (the m value) does not vary with temperature, a significant increase has been found at low pH values, suggesting that the overall dimensions of the unfolded state are significantly affected by the number of charges within the polypeptide chain. The comparison of these data with those from other small proteins indicates that the pattern of conformational stability is defined by individual sequences and not by the overall structural fold.
A Human Syndrome Caused by Immotile Cilia (1976)

Four subjects who produced immotile sperm were studied. In three of the subjects, who had frequent bronchitis and sinusitis, there was no mucociliary transport, as measured by tracheobronchial clearance. Electron microscopy indicated that cilia from cells of these patients lack dynein arms.
CTLA4–Ig fusion proteins: promise for improved therapy of transplant rejection and autoimmune diseases (2004)

T-cell activation is critically involved in the pathogenesis of both transplant rejection and autoimmunity, making its modulation a promising approach for immunotherapy. One attractive target for that purpose is provided by the CD28/B7 costimulatory pathway which is composed of the T-cell-associated CD28 molecule and its B7 ligands (CD80 and CD86) on antigen-presenting cells. This pathway is pivotal in complementing, in a non-antigenspecific manner, the antigen-specific signals of T-cell activation that are delivered upon triggering of the T-cell receptor. In the absence of CD28-mediated costimulation, T-cells activated through their T-cell receptor may acquire a state of antigen-specific unresponsiveness or undergo apoptotic cell death, leading to an abortive immune response. A competitive inhibitor of the CD28/B7 pathway has therefore been designed for use as a selective immunosuppressant. This reagent, called CTLA4–immunoglobulin (Ig), is a soluble fusion protein that binds B7 molecules with greater affinity than CD28. Extensive studies in animal models of allograft rejection and autoimmune diseases demonstrated that CTLA4–Ig exerts immunosuppressive effects without major toxicity. Over the past few years, the development of CTLA4–Ig and several analogs further proceeded to enter clinical trials in kidney transplantation, psoriasis and rheumatoid arthritis, with encouraging results. The present article will discuss the therapeutic potential of CTLA4–Ig molecules in the light of these new data.
Aging of Proteins: Immunological Detection of a Glucose-derived Pyrrole Formed during Maillard Reaction in vivo (1989)

Recent work from this laboratory revealed that glucose-derived pyrroles can form with model amines under physiological conditions (Niroge, F. G., Sayre, L. M., and Monnier, V. M. (1987) Carbohydr. Res. 167, 211-220). The major extractable product, 5-hydroxymethyl-1-alkylpyrrole-2-carbaldehyde (named by us pyrraline) was labile to acid hydrolysis. To allow its detection in proteins undergoing advanced glycosylation, an enzyme-linked immunosorbent assay was developed. An immunogen consisting of epsilon-caproyl pyrraline (hapten) was linked onto poly-L-lysine (114:1) and used to raise polyclonal antibodies in the rabbit. High antibody titers were obtained 16 weeks after immunization. The antibody cross-reacted with butyl pyrraline (88%), propyl pyrraline (8%), lysyl pyrraline (2%), and neopentyl pyrraline (1.3%). A time-related increase in pyrraline immunoreactivity was observed in bovine serum albumin incubated with glucose (1000 mM), glycated lysine (50 mM), and 3-deoxyglucosone (50 mM) which reached 25, 300, and 350 pmol/mg, respectively, after 30 days. Mean level of protein pyrraline immunoreactivity were 27.0 +/- 7.2 and 43.3 +/- 11.7 pmol/mg in serum albumin from control and diabetic subjects, respectively (p less than 0.001). The pathobiological relevance of pyrraline may relate to its reported antiproteolytic and mutagenic properties. In addition, glucose-derived pyrroles may play a role in diabetic neuropathy in analogy to pyrroles formed during hexane-induced neuropathy.
Characterization of the Heparin Binding Properties of Annexin II Tetramer (1997)

In this report, we have characterized the interaction of heparin with the Ca2+- and phospholipid-binding protein annexin II tetramer (AIIt). Analysis of the circular dichroism spectra demonstrated that the Ca2+-dependent binding of AIIt to heparin caused a large decrease in the alpha-helical content of AIIt from approximately 44 to 31%, a small decrease in the beta-sheet content from approximately 27 to 24%, and an increase in the unordered structure from 20 to 29%. The binding of heparin also decreased the Ca2+ concentration required for a half-maximal conformational change in AIIt from 360 to 84 microM. AIIt bound to heparin with an apparent Kd of 32 +/- 6 nM (mean +/- S.D., n = 3) and a stoichiometry of 11 +/- 0.9 mol of AIIt/mol of heparin (mean +/- S.D., n = 3). The binding of heparin to AIIt was specific as other sulfated polysaccharides did not elicit a conformational change in AIIt. A region of the p36 subunit of AIIt (Phe306-Ser313) was found to contain a Cardin-Weintraub consensus sequence for glycosaminoglycan recognition. A peptide to this region underwent a conformational change upon heparin binding. Other annexins contained the Cardin-Weintraub consensus sequence, but did not undergo a substantial conformational change upon heparin binding.
Characterization of the structural determinants required for the high affinity interaction of asparagine-linked oligosaccharides with immobilized Phaseolus vulgaris leukoagglutinating and erythroagglutinating lectins. (1982)

The carbohydrate binding specificities of the leukoagglutinating phytohemagglutinin (L-PHA) and erythroagglutinating phytohemagglutinin (E-PHA) lectins of the red kidney bean, Phaseolus vulgaris, have been investigated by lectin-agarose affinity chromatography of Asn-linked oligosaccharides. High affinity binding to E-PHA-agarose occurs only with biantennary glycopeptides containing 2 outer galactose residues and a residue of N-acetylglucosamine linked beta 1,4 to the beta-linked mannose residue in the core. This species is not retarded on L-PHA-agarose. In contrast, tri- and tetraanternnary glycopeptides containing outer galactose residues and an alpha-linked mannose residue substituted at positions C-2 and C-6 are specifically retarded on L-PHA-agarose. Triantennary glycopeptides containing outer galactose residues and an alpha-linked mannose residue substituted at positions C-2 and C-4 are not retarded on L-PHA-agarose. Additionally, the presence of outer sialic acid residues or a core fucose residue does not influence the behavior of complex glycopeptides on either of these lectin-agarose conjugates. This ability of E-PHA and L-PHA to discriminate between Asn-linked oligosaccharides with various branching patterns can be utilized in the fractionation of these glycopeptides (see paper following).
Reduced number of actinic keratoses with topical application of DNA repair enzyme creams. (2010)

This study suggests that DNA repair enzyme creams effectively reduce the number of actinic keratoses in normal individuals with moderate-to-severe photodamaged skin.
Flowing Concretes with Quarry Waste Fine Aggregate (2007)

Quarry waste fine aggregate has been utilized to produce flowing concretes. In total, eight flowing concrete mixtures were prepared. Except for two control concretes, quarry waste fine aggregate was used in all concretes as a partial replacement of natural pit sand. The effect of quarry waste fine aggregate was investigated with respect to flow properties (slump, slump flow, and V-funnel flow), air content, and compressive strength of concrete. It was found that quarry waste fine aggregate marginally increased the slump, slump flow, and V-funnel flow of concrete. The air content of concrete was not affected by quarry waste fine aggregate. However, the presence of quarry waste fine aggregate reduced the compressive strength of concrete by 7.2 to 9.6% at 28 and 56 days. The overall test results indicate that quarry waste fine aggregate can be utilized in flowing concretes as a substitute of natural sand.
Intraretinal Transplantation for Rod‐Cell Replacement in Light‐Damaged Retinas (1989)

Blindness from retinal disease is often the consequence of extensive damage to the photoreceptor cell population, while other cell types which form the neural retina are relatively spared. In this setting, transplantation of photoreceptor cells could offer hope for the restoration of some degree of visual function. We tested the feasibility of this approach by transplanting immature retinal cells into the eyes of adult rats affected by late stage phototoxic retinopathy, which are almost totally devoid of photoreceptor cells. Dissociated neuroretinal cells from newborn rats were injected into the hosts' retinas. These cells were labelled with the fluorescent tracer Fast-blue for identification within the host eye. Survival time ranged from 3 to 100 post-transplantation days. Fundus examination of light-irradiated eyes showed pallor caused by a considerable reduction of the retino-choroidal vascular bed after light irradiation. Histologically the hosts exhibited decimation of the elements forming the outer layers throughout the entire retina. As visualized by light and electron microscopic procedures, we report the differentiation of clusters of transplanted photoreceptor cells, and the integration of these cells within the adjacent areas of the host retina. Fluorescence microscopy showed these clusters to be formed by fluorescently labelled cells developing in intimate contact with the unlabelled host retina. Electron microscopically it was possible to determine that these photoreceptors had established synaptic contacts. These observations indicate that successful transplantation of immature retinal cells is feasible into adult eyes that have suffered extensive retino-choroidal damage. These findings also support the concept that retinal transplantation is a procedure which may open new avenues into the study of retinal repair.
Biochemical properties of hepatitis C virus NS5B RNA-dependent RNA polymerase and identification of amino acid sequence motifs essential for enzymatic activity (1997)

The NS5B protein of the hepatitis C virus (HCV) is an RNA-dependent RNA polymerase (RdRp) (S.-E. Behrens, L. Tomei, and R. De Francesco, EMBO J. 15:12-22, 1996) that is assumed to be required for replication of the viral genome. To further study the biochemical and structural properties of this enzyme, an NS5B-hexahistidine fusion protein was expressed with recombinant baculoviruses in insect cells and purified to near homogeneity. The enzyme was found to have a primer-dependent RdRp activity that was able to copy a complete in vitro-transcribed HCV genome in the absence of additional viral or cellular factors. Filter binding assays and competition experiments showed that the purified enzyme binds RNA with no clear preference for HCV 3'-end sequences. Binding to homopolymeric RNAs was also examined, and the following order of specificity was observed: poly(U) > poly(G) > poly(A) > poly(C). An inverse order was found for the RdRp activity, which used poly(C) most efficiently as a template but was inactive on poly(U) and poly(G), suggesting that a high binding affinity between polymerase and template interferes with processivity. By using a mutational analysis, four amino acid sequence motifs crucial for RdRp activity were identified. While most substitutions of conserved residues within these motifs severely reduced the enzymatic activities, a single substitution in motif D which enhanced the RdRp activity by about 50% was found. Deletion studies indicate that amino acid residues at the very termini, in particular the amino terminus, are important for RdRp activity but not for RNA binding. Finally, we found a terminal transferase activity associated with the purified enzyme. However, this activity was also detected with NS5B proteins with an inactive RdRp, with an NS4B protein purified in the same way, and with wild-type baculovirus, suggesting that it is not an inherent activity of NS5B.
Strategies for manipulating the p53 pathway in the treatment of human cancer (2000)

Human cancer progression is driven in part by the mutation of oncogenes and tumour-suppressor genes which, under selective environmental pressures, give rise to evolving populations of biochemically altered cells with enhanced tumorigenic and metastatic potential. Given that human cancers are biologically and pathologically quite distinct, it has been quite surprising that a common event, perturbation of the p53 pathway, occurs in most if not all types of human cancers. The central role of p53 as a tumour-suppressor protein has fuelled interest in defining its mechanism of function and regulation, determining how its inactivation facilitates cancer progression, and exploring the possibility of restoring p53 function for therapeutic benefit. This review will highlight the key biochemical properties of p53 protein that affect its tumour-suppressor function and the experimental strategies that have been developed for the re-activation of the p53 pathway in cancers.
Topical Treatment of Distal Ulcerative Colitis with 4-Amino-Salicylic Acid Enemas (1984)

Enemas of 4-amino-salicylic acid (4-ASA) have been compared with placebo enemas in a double-blind study for the treatment of distal ulcerative colitis of mild to moderate severity. 30 patients were randomised to receive enemas containing 1 g of 4-ASA or placebo, and 22 to receive 2-gram enemas of 4-ASA or placebo. For each dose of 4-ASA there was clinical and sigmoidoscopic improvement, which reached significance when all patients receiving 4-ASA enemas were compared with those receiving placebo enemas (Cochran's test: p less than 0.005). There was also a trend towards histological improvement, but this failed to reach the level of significance. These findings suggest that 4-ASA may provide a stable, inexpensive alternative to 5-ASA for the topical treatment of ulcerative colitis or for linking to carrier molecules for release in the colon.
Small-Molecule Inhibitors of NADPH Oxidase 4 (2010)

NOX enzymes are the major contributors in many oxidative damage related diseases. Unfortunately, at present no specific NOX inhibitor is available. Here, we describe the discovery and development of novel NOX4 inhibitors. Compound libraries were tested in a cell-based assay as a primary screen, monitoring H2O2 production. Twenty-four compounds inhibited Nox4 activity with low-micromolar IC(50) values of which three were selected for further drug development.
Isolation of a new type of human papillomavirus (HPV52b) with a transforming activity from cervical cancer tissue. (1988)

Substantial evidence has implicated human papillomaviruses (HPVs) as etiological agents of human cervical cancer. We detected and cloned an unidentified HPV genome in cellular DNA extracted from a surgical specimen of a Japanese patient with cervical cancer. Hybridization studies suggested that this HPV was the most homologous to HPV33 among more than 51 types of HPV ever identified. A recently identified new HPV, isolated by W. Lancaster and designated HPV52, is also most homologous to HPV33 (W. Lancaster et al., unpublished data). Our HPV was found to be homologous but not identical to HPV52 and hence was designated HPV52b. By introducing it into NIH3T3 cells, we found that HPV52b DNA had growth-stimulating activity as HPV16 DNA. This newly identified HPV52b DNA was present as episomes in cervical cancer cells of two out of two specimens so far examined and the integrated copies were not detected. HPV52b was present in three out of 15 (20%) specimens in Japan. In addition, the presence of three additional unidentified HPV sequences homologous to HPV52b was detected in three other specimens. The results suggest that this group of HPV may be prevalent and involved in carcinogenesis of cervical cancer in Japan.