gebhart/patrepeval huggingface dataset:
Use of the Carbon Dioxide Laser in Retarding Epithelial Migration: A Pilot Histological Human Study Utilizing Case Reports (1995)

Predictable regeneration of tooth-supporting tissues lost to periodontal disease is the aim of periodontal therapy. Often the result of conventional treatment is healing with a long junctional epithelium along the root surface and little regeneration of the complete attachment apparatus. The purpose of this pilot study was to evaluate whether de-epithelialization with a CO2 laser at the time of flap surgery and at 10-day intervals over the first 30 days of healing has the potential to enhance the formation of a connective tissue attachment. Six mandibular incisors in two patients were selected for the study. Each patient received oral hygiene instruction and initial therapy prior to surgery. The teeth were splinted together, open flap debridement was performed on all teeth, a notch was placed on the roots at the height of the crest of the alveolar bone, and the flaps were sutured in place. The test side received controlled de-epithelialization of the outer (oral) gingiva with the carbon dioxide laser, and the inner gingival flap. The de-epithelialization was repeated on the test side at 10, 20, and 30 days postsurgically. Controls received open debridement only. Block sections were taken at 90 days and processed for histologic analysis. The results showed that for both patients, junctional epithelium (JE) was formed on both test and control teeth. In all control teeth, the JE extended the entire length of the root to the base of the reference notch.(ABSTRACT TRUNCATED AT 250 WORDS)
A randomized, controlled effectiveness trial of OROS-methylphenidate compared to usual care with immediate-release methylphenidate in attention deficit-hyperactivity disorder. (2006)

Once-daily OROS-MPH is significantly more effective than usual care with IR-MPH based on multiple outcome measures including remission rate.
39-Week Toxicity and Toxicokinetic Study of Ponezumab (PF-04360365) in Cynomolgus Monkeys with 12-Week Recovery Period (2012)

Ponezumab (PF-04360365) is a novel humanized IgG2Δa monoclonal antibody that binds to amyloid-β (Aβ). It is designed to have reduced immune effector function compared to other passive immunotherapies for Alzheimer's disease (AD). Toxicity was evaluated in cynomolgus monkeys treated intravenously with vehicle or 10, 30, or 100 mg/kg of ponezumab every 10th day for up to 39 weeks, and after a 12-week recovery phase. The Aβ peptide sequence of monkeys is identical to that of humans. No substantial difference in test article exposure between sexes was observed, and mean plasma Cmax and AUC0-n were approximately dose-proportional. Ponezumab was detectable approximately 9 weeks after cessation of dosing. All animals, except two males given 10 mg/kg, maintained exposure to test article. One of these males tested positive for anti-ponezumab antibodies. Ponezumab was detected in the cerebrospinal fluid (CSF) of animals given active treatment. The estimated CSF/plasma ponezumab concentration ratio was <0.008 after multiple doses. At the end of the dosing and recovery phases, plasma Aβ1-40 and Aβ1-x were increased in treated animals versus controls. No test article-related effects were seen after ophthalmogical, cardiovascular, physical examinations, and clinical and anatomic pathology evaluations. Plasma concentrations of ponezumab on day 261 at the no observed adverse effect level of 100 mg/kg were 22.4 and 5.3 times greater on a Cmax and AUC basis, respectively, than human exposures at the highest dose (10 mg/kg) in a single-dose Phase I trial. These data suggest an acceptable safety profile for ponezumab as an immunotherapy for AD.
Iodination Reactions of Icosahedral para-Carborane and the Synthesis of Carborane Derivatives with Boron-Carbon Bonds (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIodination Reactions of Icosahedral para-Carborane and the Synthesis of Carborane Derivatives with Boron-Carbon BondsWei Jiang, Carolyn B. Knobler, Carol E. Curtis, Mark D. Mortimer, and M. Frederick HawthorneCite this: Inorg. Chem. 1995, 34, 13, 3491–3498Publication Date (Print):June 1, 1995Publication History Published online1 May 2002Published inissue 1 June 1995https://pubs.acs.org/doi/10.1021/ic00117a018https://doi.org/10.1021/ic00117a018research-articleACS PublicationsRequest reuse permissionsArticle Views677Altmetric-Citations81LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
The Inactivation of Human C1 by Benzamidine and Pyridinium Sulfonylfluorides (1974)

Abstract Affinity chromatographically purified C1̄ was demonstrated to be inhibitable by a variety of benzamidine and pyridinium fluorosulfonyl-substituted compounds. Four of the compounds tested afforded greater than 50% inhibition at concentrations between 10-6 and 10-5 M. The data indicated that inhibition was greatest with those compounds which contained a substituted benzamidine and sulfonyl-fluoride group. The site of action was the esterase activity associated with the C1.
Use of a cDNA clone for the fourth component of human complement (C4) for analysis of a genetic deficiency of C4 in guinea pig. (1983)

A cDNA clone for the fourth complement component (C4), pC4AL1, has been isolated from a human adult liver cDNA library by using a synthetic oligonucleotide mixture containing all 384 possible sequences coding for residues 14-21 of the C4 gamma-chain amino acid sequence. This clone spans the entire C4 gamma-chain coding sequence and includes a short 3' untranslated region, a poly(A) recognition site, and 16 nucleotides of the poly(A) tail. The 5' end of the clone begins 18 nucleotides upstream from the amino terminus of the C4 gamma chain and codes for Arg-Asn-Arg-Arg-Arg-Arg, a highly charged proteolytic cleavage site involved in the processing of pro-C4 to native C4. Liver mRNA preparations from C4-deficient guinea pigs were incapable of directing synthesis of pro-C4 or C4 peptides in cell-free translation experiments. Southern blot analysis using pC4AL1 as a hybridization probe of C4-deficient guinea pig DNA established that the deficiency is not the result of deletion of the entire C4 gene. RNA blot analysis using pC4AL1 as a hybridization probe of normal guinea pig liver mRNA revealed a C4 mRNA of 5.0 kilobases (kb). No such mRNA species was observed in C4-deficient guinea pig liver mRNA; however, a 7.0-kb RNA was detected, indicating the presence of a C4 precursor RNA. These results suggest that the basis of C4 deficiency in the guinea pig is a post-transcriptional defect in the processing of C4 precursor RNA to mature C4 mRNA.
Molecular Analysis of T Cell Clonotypes in Muscle‐Infiltrating Lymphocytes from Patients with Human T Lymphotropic Virus Type 1 Polymyositis (2002)

Epidemiological studies have shown that a correlation may exist between human T cell lymphotropic virus type 1 (HTLV-1) infection and a form of polymyositis (PM). To characterize muscle-infiltrating lymphocytes (MILs) from patients with HTLV-1 PM, we examined the T cell receptor (TCR) beta-chain variable region repertoire and clonotype of MILs and peripheral blood mononuclear cells (PBMC) from 3 patients, using TCR complementarity-determining region 3 (CDR3) length spectratyping and DNA sequencing. Immunohistochemical studies showed that MILs from patients with HTLV-1 PM contain both CD4(+) and CD8(+) T cells. Although some clonotypes observed in PBMC were also found in MILs in all patients examined, MILs consisted predominantly of locally expanded clones. One clonotype in MILs was derived from human leukocyte antigen (HLA)-A*02/Tax11-19 tetramer-positive cells, the CDR3 motif of which contains amino acid residues for HLA-A*02/Tax peptide-TCR interaction. We conclude that certain T cell clones proliferate in the muscle lesions of HTLV-1 PM and may contribute to the pathogenesis of the disease.
Modeling of bubble dynamics in relation to medical applications (1997)

In various pulsed-laser medical applications, strong stress transients can be generated in advance of vapor bubble formation. To better understand the evolution of stress transients and subsequent formation of vapor bubbles, two-dimensional simulations are presented in channel or cylindrical geometry with the LATIS (LAser TISsue) computer code. Differences with one-dimensional modeling are explored, and simulated experimental conditions for vapor bubble generation are presented and compared with data. 22 refs., 8 figs.
STRUCTURAL STUDIES ON SOIL HUMIC ACIDS BY CURIE-POINT PYROLYSIS-GAS CHROMATOGRAPHY/MASS SPECTROMETRY (1992)

Humic acids (HAs) extracted from the Ap horizon of a Haplaquoll (Bainsville) and the Bh horizon of a Haplaquod (Armadale) were investigated by Curie-point pyrolysis (Cp Py)-gas chromatography (GC)/mass spectrometry (MS). More than 300 pyrolysis products, tentatively identified by conventional electron impact (EI) and field ionization (FI) MS, were common to both samples, although very different in their intensity distributions. Whereas the Armadale HA produced predominantly alkanes and olefins, the Bainsville HA yielded large quantities of phenol derivatives. Alkanes and olefins formed homologous series up to C30 and n-alkylbenzenes up to C18. Of particular interest were the intense signals originating from aromatics and alkyl-substituted aromatics, especially phenol derivatives and methyl-substituted naphthalenes. In addition, heterocyclic compounds such as furans, pyrroles, and pyridines with and without alkyl substituents were also detected. Our data indicate the presence of aryl-alkyl structures in the HA network and contribute to a better understanding of the chemical composition and structure of soil organic matter (SOM).
Pharmacological incompatibility (2003)

In the lecture there have been studied pharmacokinetic and pharmacodynamic mechanisms of drug undesirable interaction at combined pharmacotherapy and have been cited the urgent for general practitioner examples of pharmacological incompatibility.
Hyperforin Inhibits Cancer Invasion and Metastasis (2004)

Hyperforin (Hyp), the major lipophilic constituent of St. John's wort, was assayed as a stable dicyclohexylammonium salt (Hyp-DCHA) for cytotoxicity and inhibition of matrix proteinases, tumor invasion, and metastasis. Hyp-DCHA triggered apoptosis-associated cytotoxic effect in both murine (C-26, B16-LU8, and TRAMP-C1) and human (HT-1080 and SK-N-BE) tumor cells; its effect varied, with B16-LU8, HT-1080, and C-26 the most sensitive (IC50 = 5 to 8 micromol/L). At these concentrations, a marked and progressive decline of growth was observed in HT-1080 cells, whereas untransformed endothelial cells were only marginally affected. Hyp-DCHA inhibited in a dose-dependent and noncompetitive manner various proteinases instrumental to extracellular matrix degradation; the activity of leukocyte elastase was inhibited the most (IC50 = 3 micromol/L), followed by cathepsin G and urokinase-type plasminogen activator, whereas that of the matrix metalloproteinases (MMPs) 2 and 9 showed an IC50 > 100 micromol/L. Nevertheless, inhibition of extracellular signal-regulated kinase 1/2 constitutive activity and reduction of MMP-2 and MMP-9 secretion was triggered by 0.5 micromol/L Hyp-DCHA to various degrees in different cell lines, the most in C-26. Inhibition of C-26 and HT-1080 cell chemoinvasion (80 and 54%, respectively) through reconstituted basement membrane was observed at these doses. Finally, in mice that received i.v. injections of C-26 or B16-LU8 cells, daily i.p. administration of Hyp-DCHA-without reaching tumor-cytotoxic blood levels-remarkably reduced inflammatory infiltration, neovascularization, lung weight (-48%), and size of experimental metastases with C-26 (-38%) and number of lung metastases with B16-LU8 (-22%), with preservation of apparently healthy and active behavior. These observations qualify Hyp-DCHA as an interesting lead compound to prevent and contrast cancer spread and metastatic growth.
Site‐Specific Protein Labeling via Sortase‐Mediated Transpeptidation (2009)

Creation of functional protein bioconjugates demands methods for attaching a diverse array of probes to target proteins with high specificity, under mild conditions. The sortase A transpeptidase enzyme from Staphylococcus aureus catalyzes the cleavage of a short 5-aa recognition sequence (LPXTG) with the concomitant formation of an amide linkage between an oligoglycine peptide and the target protein. By functionalizing the oligoglycine peptide, it is possible to incorporate reporters into target proteins in a site-specific fashion. This reaction is applicable to proteins in solution and on the living cell surface. The method described in this unit only requires incubation of the target protein, which has been engineered to contain a sortase recognition site either at the C terminus or within solvent-accessible loops, with a purified sortase enzyme and a suitably functionalized oligoglycine peptide.
Identification of a Benzoisoxazoloazepine Inhibitor (CPI-0610) of the Bromodomain and Extra-Terminal (BET) Family as a Candidate for Human Clinical Trials (2016)

In recent years, inhibition of the interaction between the bromodomain and extra-terminal domain (BET) family of chromatin adaptors and acetyl-lysine residues on chromatin has emerged as a promising approach to regulate the expression of important disease-relevant genes, including MYC, BCL-2, and NF-κB. Here we describe the identification and characterization of a potent and selective benzoisoxazoloazepine BET bromodomain inhibitor that attenuates BET-dependent gene expression in vivo, demonstrates antitumor efficacy in an MV-4-11 mouse xenograft model, and is currently undergoing human clinical trials for hematological malignancies (CPI-0610).
A senescent cell bystander effect: senescence‐induced senescence (2012)

Senescent cells produce and secrete various bioactive molecules including interleukins, growth factors, matrix-degrading enzymes and reactive oxygen species (ROS). Thus, it has been proposed that senescent cells can damage their local environment, and a stimulatory effect on tumour cell growth and invasiveness has been documented. However, it was unknown what effect, if any, senescent cells have on their normal, proliferation-competent counterparts. We show here that senescent cells induce a DNA damage response, characteristic for senescence, in neighbouring cells via gap junction-mediated cell-cell contact and processes involving ROS. Continuous exposure to senescent cells induced cell senescence in intact bystander fibroblasts. Hepatocytes bearing senescence markers clustered together in mice livers. Thus, senescent cells can induce a bystander effect, spreading senescence towards their neighbours in vitro and, possibly, in vivo.
Multiple-Drug Resistant Enterococci: The Nature of the Problem and an Agenda for the Future (1998)

Enterococci, leading causes of nosocomial bacteremia, surgical wound infection, and urinary tract infection, are becoming resistant to many and sometimes all standard therapies. New rapid surveillance methods are highlighting the importance of examining enterococcal isolates at the species level. Most enterococcal infections are caused by Enterococcus faecalis, which are more likely to express traits related to overt virulence but--for the moment--also more likely to retain sensitivity to at least one effective antibiotic. The remaining infections are mostly caused by E. faecium, a species virtually devoid of known overt pathogenic traits but more likely to be resistant to even antibiotics of last resort. Effective control of multiple-drug resistant enterococci will require 1) better understanding of the interaction between enterococci, the hospital environment, and humans, 2) prudent antibiotic use, 3) better contact isolation in hospitals and other patient care environments, and 4) improved surveillance. Equally important is renewed vigor in the search for additional drugs, accompanied by the evolution of new therapeutic paradigms less vulnerable to the cycle of drug introduction and drug resistance.
Organ-specific gene expression in the rhesus monkey eye following intravenous non-viral gene transfer. (2003)

The PIL non-viral gene transfer technology makes possible adult transgenics in 24 h. Ectopic expression of exogenous genes in organs other than the target organ is made possible with the use of organ specific promoters, and gene expression in the primate is restricted to the eye when the trans-gene is under the influence of the opsin promoter. Plasmid-based gene expression is still in the therapeutic range for 2-3 weeks after a single intravenous administration. Exogenous genes are expressed throughout the entire primate retina following the delivery of the gene to the eye via a trans-vascular route.
Mode of dimerization of HIV-1 genomic RNA (1993)

Retroviral genomes consist of two identical RNA molecules joined noncovalently near their 5' ends, at domains called dimerization linked sequences (DLS). This physical linkage of the genomic RNAs is considered important for the control of several steps in the viral life cycle, such as recombination, translation, and encapsidation. The putative DLS of human immunodeficiency virus-1 (HIV-1), a 111-nucleotide, purine-rich stretch of RNA, has been found necessary and sufficient for a salt-induced dimerization of the genome in vitro. Our investigation into the mechanism of this dimerization reveals sharply varying influences of the different alkali cations on both the formation and the stabilization of the dimer, a pattern closely related to that of telomeric G-DNA complexes. To probe this phenomenon, we have carried out experiments using short antisense DNA oligomers to define the segments of the DLS that are required for dimerization and methylation protection to implicate sets of guanines in forming Hoogsteen hydrogen bonds within the dimer. Cumulatively, these data provide further evidence for the existence of guanine quartets within the dimerized HIV-1 DLS. We propose models in which guanine quartets not only allow the homodimerization of HIV-1 and other retroviral genomic RNAs but also permit the two RNA strands in a dimer to exist in an overall parallel orientation, as has been observed by electron microscopy.
Human T‐Lymphoid Progenitors Generated in a Feeder‐Cell‐Free Delta‐Like‐4 Culture System Promote T‐Cell Reconstitution in NOD/SCID/γc −/− Mice (2012)

Slow T-cell reconstitution is a major clinical concern after transplantation of cord blood (CB)-derived hematopoietic stem cells. Adoptive transfer of in vitro-generated T-cell progenitors has emerged as a promising strategy for promoting de novo thymopoiesis and thus accelerating T-cell reconstitution. Here, we describe the development of a new culture system based on the immobilized Notch ligand Delta-like-4 (DL-4). Culture of human CD34(+) CB cells in this new DL-4 system enabled the in vitro generation of large amounts of T-cell progenitor cells that (a) displayed the phenotypic and molecular signatures of early thymic progenitors and (b) had high T lymphopoietic potential. When transferred into NOD/SCID/γc(-/-) (NSG) mice, DL-4 primed T-cell progenitors migrated to the thymus and developed into functional, mature, polyclonal αβ T cells that subsequently left the thymus and accelerated T-cell reconstitution. T-cell reconstitution was even faster and more robust when ex vivo-manipulated and nonmanipulated CB samples were simultaneously injected into NSG mice (i.e., a situation reminiscent of the double CB transplant setting). This work provides further evidence of the ability of in vitro-generated human T-cell progenitors to accelerate T-cell reconstitution and also introduces a feeder-cell-free culture technique with the potential for rapid, safe transfer to a clinical setting.
3-D image models and compression: synthetic hybrid or natural fit? (1999)

This paper highlights recent advances in image compression aided by 3-D geometry information. As two examples, we present a model-aided video coder for efficient compression of head-and-shoulder scenes and a geometry-aided coder for 4-D light fields for image-based rendering. Both examples illustrate that an explicit representation of 3-D geometry is advantageous if many views of the same 3-D object or scene have to be encoded. Waveform-coding and 3-D model-based coding can be combined in a rate-distortion framework, such that the generality of waveform coding and the efficiency of 3-D models are available where needed.
p62/SQSTM1 Binds Directly to Atg8/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy (2007)

Protein degradation by basal constitutive autophagy is important to avoid accumulation of polyubiquitinated protein aggregates and development of neurodegenerative diseases. The polyubiquitin-binding protein p62/SQSTM1 is degraded by autophagy. It is found in cellular inclusion bodies together with polyubiquitinated proteins and in cytosolic protein aggregates that accumulate in various chronic, toxic, and degenerative diseases. Here we show for the first time a direct interaction between p62 and the autophagic effector proteins LC3A and -B and the related gamma-aminobutyrate receptor-associated protein and gamma-aminobutyrate receptor-associated-like proteins. The binding is mediated by a 22-residue sequence of p62 containing an evolutionarily conserved motif. To monitor the autophagic sequestration of p62- and LC3-positive bodies, we developed a novel pH-sensitive fluorescent tag consisting of a tandem fusion of the red, acid-insensitive mCherry and the acid-sensitive green fluorescent proteins. This approach revealed that p62- and LC3-positive bodies are degraded in autolysosomes. Strikingly, even rather large p62-positive inclusion bodies (2 microm diameter) become degraded by autophagy. The specific interaction between p62 and LC3, requiring the motif we have mapped, is instrumental in mediating autophagic degradation of the p62-positive bodies. We also demonstrate that the previously reported aggresome-like induced structures containing ubiquitinated proteins in cytosolic bodies are dependent on p62 for their formation. In fact, p62 bodies and these structures are indistinguishable. Taken together, our results clearly suggest that p62 is required both for the formation and the degradation of polyubiquitin-containing bodies by autophagy.