gebhart/patrepeval huggingface dataset:
Minimal intervention dentistry: part 1. Strategies for addressing the new caries challenge in older patients. (2006)

The aging of the population combined with increased retention of natural teeth into old age means that clinicians now face a new caries challenge in older dentate patients. An increase in the onset of dental caries is evident among patients who may not have had high levels of caries in the past and who may have undergone extensive restorative procedures during their lifetimes. Minimal intervention dentistry (MID), a modern evidence-based approach to caries management in dentate patients, uses the medical model, whereby disease is controlled by the "oral physician" and an affiliated dental team. The main components of a geriatric approach to MID are assessment of the risk of disease, with a focus on early detection and prevention; external and internal remineralization; use of a range of restorations, dental materials and equipment; and surgical intervention only when required and only after disease has been controlled. This first in a series of 2 articles describes and illustrates oral disease management in geriatric MID, which involves the assessment and management of a diverse range of primary and modifying factors, integrated with an evaluation of the plaque-biofilm interface and the resultant dynamic oral disease process.
Tendon Graft Substitutes???Rotator Cuff Patches (2006)

Over the past few years, many biologic patches have been developed to augment repairs of large or complex tendon tears. These patches include both allograft and xenografts. Regardless of their origins, these products are primarily composed of purified type I collagen. Many factors should be considered when choosing an augmentation patch including tissue origin, graft processing, cross-linking, clinical experience, and physical properties. The purpose of this article is to familiarize the sports medicine community with several tendon augmentation grafts: GraftJacket (Wright Medical Technology, Arlington, TN), CuffPatch (Organogenesis, Canton, MA, licensed to Arthrotek, Warsaw, IN), Restore (Depuy, Warsaw, IN), Zimmer Collagen Repair (Permacol) patch (Tissue Science Laboratories Covington, GA, licensed to Zimmer, Warsaw, IN), TissueMend (TEI Biosciences, Boston, MA, licensed to Stryker Howmedica Osteonics, Kalamazoo, MI), OrthoADAPT (Pegasus Biologics, Irvine, CA), and BioBlanket (Kensey Nash, Exton, PA).
S100A8: emerging functions and regulation (1999)

The functional importance of members of the S100 Ca2+-binding protein family is becoming apparent. Murine (m)S100A8 (initially named CP-10) is a potent chemoattractant (10(-13) to 10(-11) M) for myeloid cells and the chemotactic activity of other S100s has since been reported, suggesting a new class of chemoattractants. Murine S100A8 has been associated with a number of acute and chronic inflammatory conditions including bacterial infection, atherogenesis, and cystic fibrosis. It is expressed constitutively with S100A9 in neutrophils and is regulated by inflammatory stimulants in macrophages and microvascular endothelial cells. The lack of co-expression of S100A9 with S100A8 in activated macrophages suggests distinct functions for the proteins expressed by different cell types. Glucocorticoids up-regulate induction of mS100A8 by inflammatory mediators, and its exquisite sensitivity to oxidation suggests that it may protect against oxidative tissue damage. Inactivation of the mS100A8 gene is embryonic lethal, providing the first evidence for non-redundant function of a member of the S100 gene family. S100A8 may have an immunoregulatory role by contributing to the regulation of fetal-maternal interactions. It may play a protective role and its absence may allow infiltration by maternal cells, a process eventually manifesting as resorption. This review focuses on the variety of emerging functions attributed to murine S100A8, a protein implicated in embryogenesis, growth, differentiation, and immune and inflammatory processes.
Molecular conservation of the P6 outer membrane protein among strains of Haemophilus influenzae: analysis of antigenic determinants, gene sequences, and restriction fragment length polymorphisms (1991)

Infections caused by Haemophilus influenzae are a major worldwide health problem. In particular, nontypeable strains of H. influenzae are a common cause of otitis media in infants and children. A vaccine to prevent these infections would result in the prevention of substantial morbidity and cost savings. A problem in identifying an appropriate vaccine antigen has been the enormous antigenic heterogeneity among nontypeable strains of H. influenzae. The present study was undertaken to characterize the conservation of the P6 outer membrane protein (approximately 16,000 daltons) among strains of H. influenzae. A total of 20 type b strains and 20 nontypeable strains of diverse geographic and clinical origins was studied. Three approaches were taken. (i) Antigenic determinants recognized by monoclonal and polyclonal antibodies were present on P6 in all 40 strains tested. The molecular weight of P6 was identical in all strains. (ii) Comparison of the DNA sequences of the P6 genes from three epidemiologically and serologically unrelated strains demonstrated 100% homology at the amino acid level and 97 to 99% homology at the nucleotide level. (iii) Restriction fragment length polymorphism analysis demonstrated that the P6 gene and flanking sequences were highly conserved among all strains. These three independent series of experiments indicated that the P6 protein is highly conserved among strains of H. influenzae. P6 should receive serious consideration for inclusion in a vaccine to prevent infections caused by nontypeable H. influenzae.
Trends and Challenges in Experimental Macromolecular Crystallography (1996)

Macromolecular X-ray crystallography underpins the vigorous field of structural molecular biology having yielded many protein, nucleic acid and virus structures in fine detail. The understanding of the recognition by these macromolecules, as receptors, of their cognate ligands involves the detailed study of the structural chemistry of their molecular interactions. Also these structural details underpin the rational design of novel inhibitors in modern drug discovery in the pharmaceutical industry. Moreover, from such structures the functional details can be inferred, such as the biological chemistry of enzyme reactivity. There is then a vast number and range of types of biological macromolecules that potentially could be studied. The completion of the protein primary sequencing of the yeast genome, and the human genome sequencing project comprising some 10 5 proteins that is underway, raises expectations for equivalent three dimensional structural databases.
Convolutional neural networks can accurately distinguish four histologic growth patterns of lung adenocarcinoma in digital slides (2019)

During the diagnostic workup of lung adenocarcinomas (LAC), pathologists evaluate distinct histological tumor growth patterns. The percentage of each pattern on multiple slides bears prognostic significance. To assist with the quantification of growth patterns, we constructed a pipeline equipped with a convolutional neural network (CNN) and soft-voting as the decision function to recognize solid, micropapillary, acinar, and cribriform growth patterns, and non-tumor areas. Slides of primary LAC were obtained from Cedars-Sinai Medical Center (CSMC), the Military Institute of Medicine in Warsaw and the TCGA portal. Several CNN models trained with 19,924 image tiles extracted from 78 slides (MIMW and CSMC) were evaluated on 128 test slides from the three sites by F1-score and accuracy using manual tumor annotations by pathologist. The best CNN yielded F1-scores of 0.91 (solid), 0.76 (micropapillary), 0.74 (acinar), 0.6 (cribriform), and 0.96 (non-tumor) respectively. The overall accuracy of distinguishing the five tissue classes was 89.24%. Slide-based accuracy in the CSMC set (88.5%) was significantly better (p < 2.3E-4) than the accuracy in the MIMW (84.2%) and TCGA (84%) sets due to superior slide quality. Our model can work side-by-side with a pathologist to accurately quantify the percentages of growth patterns in tumors with mixed LAC patterns.
Determination of a correction to improve mass measurement accuracy of isotopically unresolved polymerase chain reaction amplicons by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (2003)

The experimental determination of average mass by mass spectrometry is limited for large molecules due to the negative bias introduced by the natural distribution of isotopic abundances. This results in the measurement of the top-of-centroid (ToC) as opposed to the true centroid. We have developed a practical correction factor that is applied to the ToC measurement to largely remove the systematic bias introduced by nature. The correction factor is calculated easily using the average molecular mass (<100 kDa) of the analyte molecule and the full-width half maximum resolving power (<3,500) of the measurement. In addition, an approach to calculating resolving power is described that accurately predicts resolving power achievable for Fourier transform ion cyclotron resonance (FT-ICR) mass analysis of large molecules. A combination of internal calibration with a dual-electrospray source and application of the correction factor to average mass measurements improved the mass error from 192.5 to -35.0 ppm for a 44 kDa PCR amplicon.
Synthesis of Cetuximab-Immunoliposomes via a Cholesterol-Based Membrane Anchor for Targeting of EGFR (2006)

The objective of the present study was to construct epidermal growth factor receptor (EGFR) targeting cetuximab-immunoliposomes (ILs) for targeted delivery of boron compounds to EGFR(+) glioma cells for neutron capture therapy. The ILs were synthesized by using a novel cholesterol-based membrane anchor, maleimido-PEG-cholesterol (Mal-PEG-Chol), to incorporate cetuximab into liposomes by either surface conjugation or a post-insertion method. For post-insertion, the transfer efficiency of MAb conjugates from micelles to liposome was examined at varying temperatures, mPEG2000-DSPE ratios, and micelle-to-liposome lipid ratios. Following this, the cetuximab-ILs were evaluated for targeted delivery of the encapsulated boron anion, dodecahydro-closo-dodecaborate (2-) (B12H122-), to human EGFR gene transfected F98EGFR glioma cells as potential delivery agents for boron neutron capture therapy (BNCT). In addition, cellular uptake of cetuximab-ILs, encapsulating a fluorescence dye, was analyzed by confocal fluorescence microscopy and flow cytometry, and boron content was quantified by ICP-MS. Much greater ( approximately 8-fold) cellular uptake of boron was obtained using cetuximab-ILs in EGFR(+) F98EGFR compared with nontargeted human IgG-ILs. On the basis of these observations, we have concluded that cholesterol can serve as an effective anchor for MAb in liposomes, and cetuximab-ILs are potentially useful delivery vehicles for BNCT of gliomas.
Spectroscopic probing of the influence of calcium and the Gla domain on the interaction between the first EGF domain in factor VIIa and tissue factor (2000)

The binding of factor VIIa (FVIIa) to tissue factor (TF) initiates blood coagulation. The binary complex is dependent on Ca2+ binding to several sites in FVIIa and is maintained by multiple contacts distributed throughout the various domains. Although the contributions from various residues and domains, including the Ca2+ coordination, to the global binding energy have been characterized, their importance for specific local interactions is virtually unknown. To address this aspect, we have attached four spectroscopic probes to an engineered Cys residue replacing Phe140 in soluble TF (sTF). This allows the monitoring of local changes in hydrophobicity and rigidity upon complex formation at the interface between the first epidermal growth factor-like (EGF1) domain of FVIIa and sTF. The fluorescent labels used sense a more hydrophobic environment and the spin labels are dramatically immobilized when FVIIa binds sTF. The results obtained with a 4-carboxyglutamic acid (Gla)-domainless derivative of FVIIa indicate that the Gla domain has no or minimal influence on the interaction between EGF1 and sTF. However, there is a difference in local Ca2+ dependence between Gla-domainless and full-length FVIIa.
Room-temperature deep-ultraviolet lasing at 241.5 nm of AlGaN multiple-quantum-well laser (2004)

Room-temperature deep-ultraviolet lasing of AlxGa1−xN multiple-quantum-well lasers with an Al composition x of 0.66 was achieved at 241.5 nm under pulsed optical pumping. The threshold pumping power was approximately 1200 kW/cm2 at room temperature. The shortest lasing wavelength was 231.8 nm at 20 K. The laser structure was grown on a high-quality AlN layer, which was grown on a 4H-SiC substrate by inserting an AlN/GaN multibuffer-layer structure between the substrate and the AlN layer. Temperature dependence of lasing wavelength was also estimated to be 0.01 and 0.03 nm/K in the temperature region from 20 to 150 K and from 160 K to room temperature, respectively. The laser cavity was made of a cleaved facet of AlGaN epitaxial layers and a SiC substrate. For this purpose, it was necessary to polish the wafer to a thickness of less than 100 μm. The optimal wafer thickness for cleaving in our experiments was 60–70 μm.
Evaluation of Hepatitis C Virus Glycoprotein E2 for Vaccine Design: an Endoplasmic Reticulum-Retained Recombinant Protein Is Superior to Secreted Recombinant Protein and DNA-Based Vaccine Candidates (2000)

Hepatitis C virus (HCV) is the leading causative agent of blood-borne chronic hepatitis and is the target of intensive vaccine research. The virus genome encodes a number of structural and nonstructural antigens which could be used in a subunit vaccine. The HCV envelope glycoprotein E2 has recently been shown to bind CD81 on human cells and therefore is a prime candidate for inclusion in any such vaccine. The experiments presented here assessed the optimal form of HCV E2 antigen from the perspective of antibody generation. The quality of recombinant E2 protein was evaluated by both the capacity to bind its putative receptor CD81 on human cells and the ability to elicit antibodies that inhibited this binding (NOB antibodies). We show that truncated E2 proteins expressed in mammalian cells bind with high efficiency to human cells and elicit NOB antibodies in guinea pigs only when purified from the core-glycosylated intracellular fraction, whereas the complex-glycosylated secreted fraction does not bind and elicits no NOB antibodies. We also show that carbohydrate moieties are not necessary for E2 binding to human cells and that only the monomeric nonaggregated fraction can bind to CD81. Moreover, comparing recombinant intracellular E2 protein to several E2-encoding DNA vaccines in mice, we found that protein immunization is superior to DNA in both the quantity and quality of the antibody response elicited. Together, our data suggest that to elicit antibodies aimed at blocking HCV binding to CD81 on human cells, the antigen of choice is a mammalian cell-expressed, monomeric E2 protein purified from the intracellular fraction.
Evaluation of a Test Based on Baculovirus-Expressed Glycoprotein G for Detection of Herpes Simplex Virus Type-Specific Antibodies (1991)

An immunoblot assay for discrimination of antibodies to herpes simplex virus (HSV) types 1 and 2 was devised using extracts of recombinant-baculovirus-infected insect cells expressing HSV-1 or -2 glycoprotein G (gG1 or gG2). The assay was evaluated by comparing its results with those obtained by using an immunodot assay based on gG immunopurified from HSV-1- and HSV-2-infected cells. Each of 110 human serum specimens was tested blindly and independently three times. At a serum dilution of 1:20, the maximum specificities were 96% and 100% and the maximum sensitivities were 100% and 92% for gG1 and gG2, respectively. Reproducibility was 99% among readers and 95% among individually tested samples of each specimen. Results obtained in two laboratories from a different set of 15 serum specimens were in complete agreement, indicating the assay is accurate and reproducible. The ease of antigen production should allow the test to become widely available.
Laparoscopic access: complications, technologies, and techniques (2002)

The incidence and spectrum of access-related complications is greater than previously perceived. Newer devices and modifications in technique may reduce the incidence of such adverse events.
Fibroblast growth factor 2 endocytosis in endothelial cells proceed via syndecan-4-dependent activation of Rac1 and a Cdc42-dependent macropinocytic pathway (2004)

Full activity of fibroblast growth factors (FGFs) requires their internalization in addition to the interaction with cell surface receptors. Recent studies have suggested that the transmembrane proteoglycan syndecan-4 functions as a FGF2 receptor. In this study we investigated the molecular basis of syndecan endocytosis and its role in FGF2 internalization in endothelial cells. We found that syndecan-4 uptake, induced either by treatment with FGF2 or by antibody clustering, requires the integrity of plasma membrane lipid rafts for its initiation, occurs in a non-clathrin-, non-dynamin-dependent manner and involves Rac1, which is activated by syndecan-4 clustering. FGF2 was internalized in a complex with syndecan-4 in 70 kDa dextran-containing endocytic vesicles. FGF2 and syndecan-4 but not dextran endocytosis were blocked by the dominant negative Rac1 while amiloride and the dominant-negative Cdc42 blocked internalization of dextran in addition to FGF2 and syndecan-4. Taken together, these results demonstrate that FGF2 endocytosis requires syndecan-4 clustering-dependent activation of Rac1 and the intact CDC42-dependent macropinocytic pathway.
9.1: Arc Stabilisation for Short Arc Projection Lamps (2000)

Abstract UHP‐lamps are standard for high efficient projection systems. All short arc lamps show arc instabilities. Optical integrators can successfully suppress visual effects but they are of limited use for small displays. A new technology is presented here which stabilises the lamp arc directly and keeps the good maintenance of the lamp.
Interactions of stabilizing additives with proteins during freeze-thawing and freeze-drying. (1992)

A wide variety of compounds, including sugars, polyols, amino acids and certain salts, are effective at minimizing protein denaturation during freeze-thawing. In this review we provide evidence that the mechanistic basis for this cryoprotection appears to be the same as that described by Timasheff for solute-induced stabilization in aqueous solution. Namely, the stabilizers are preferentially excluded from the surface of the protein, and this interaction makes it thermodynamically unfavourable for proteins to unfold. In contrast, carbohydrate-induced preservation of labile enzymes during freeze-drying is a fundamentally different process. Using Fourier transform intra-red spectroscopy we have found that hydrogen bonding between the carbohydrate and the dried protein is required for stabilization. Thus, it appears that certain carbohydrates protect dried enzymes because these solutes serve as water substitutes for the dried protein, by satisfying the hydrogen bonding requirement of polar groups on the protein's surface. Finally, we discuss some intriguing findings on the synergistic stabilization of proteins by mixtures of divalent cations and organic solutes, which are yet to be explained.
Increased Expression and Immunogenicity of Sequence-Modified Human Immunodeficiency Virus Type 1 gag Gene (2000)

A major challenge for the next generation of human immunodeficiency virus (HIV) vaccines is the induction of potent, broad, and durable cellular immune responses. The structural protein Gag is highly conserved among the HIV type 1 (HIV-1) gene products and is believed to be an important target for the host cell-mediated immune control of the virus during natural infection. Expression of Gag proteins for vaccines has been hampered by the fact that its expression is dependent on the HIV Rev protein and the Rev-responsive element, the latter located on the env transcript. Moreover, the HIV genome employs suboptimal codon usage, which further contributes to the low expression efficiency of viral proteins. In order to achieve high-level Rev-independent expression of the Gag protein, the sequences encoding HIV-1(SF2) p55(Gag) were modified extensively. First, the viral codons were changed to conform to the codon usage of highly expressed human genes, and second, the residual inhibitory sequences were removed. The resulting modified gag gene showed increases in p55(Gag) protein expression to levels that ranged from 322- to 966-fold greater than that for the native gene after transient expression of 293 cells. Additional constructs that contained the modified gag in combination with modified protease coding sequences were made, and these showed high-level Rev-independent expression of p55(Gag) and its cleavage products. Density gradient analysis and electron microscopy further demonstrated that the modified gag and gag protease genes efficiently expressed particles with the density and morphology expected for HIV virus-like particles. Mice immunized with DNA plasmids containing the modified gag showed Gag-specific antibody and CD8(+) cytotoxic T-lymphocyte (CTL) responses that were inducible at doses of input DNA 100-fold lower than those associated with plasmids containing the native gag gene. Most importantly, four of four rhesus monkeys that received two or three immunizations with modified gag plasmid DNA demonstrated substantial Gag-specific CTL responses. These results highlight the useful application of modified gag expression cassettes for increasing the potency of DNA and other gene delivery vaccine approaches against HIV.
Genomic Subtraction Identifies Salmonella typhimurium Prophages, F-Related Plasmid Sequences, and a Novel Fimbrial Operon, stf , Which Are Absent in Salmonella typhi (1999)

Salmonella typhimurium causes systemic and fatal infection in inbred mice, while the related serotype Salmonella typhi is avirulent for mammals other than humans. In order to identify genes from the virulent strain S. typhimurium ATCC 14028 that are absent in S. typhi Ty2, and therefore might be involved in S. typhimurium mouse virulence, a PCR-supported genomic subtractive hybridization procedure was employed. We have identified a novel putative fimbrial operon, stfACDEFG, located at centisome 5 of the S. typhimurium chromosome, which is absent in S. typhi, Salmonella arizonae, and Salmonella bongori but was detected in several other Salmonella serotypes. The fimbrial genes represent a genomic insertion in S. typhimurium compared to the respective region between fhuB and hemL in Escherichia coli K-12. In addition, the subtraction procedure yielded F plasmid-related sequences from the S. typhimurium virulence plasmid, a number of DNA fragments representing parts of lambdoid prophages and putative sugar transporters, and several fragments with unknown sequences. The majority of subtracted chromosomal sequences map to three distinct locations, around centisomes 5, 27, and 57.