gebhart/patrepeval huggingface dataset:
Evaluation of bone ingrowth in proximally and extensively porous-coated anatomic medullary locking prostheses retrieved at autopsy. (1995)

Three proximally (40 per cent) and five extensively (80 per cent) porous-coated anatomic medullary locking femoral components were retrieved from seven cadavera at autopsy. Each component (with the surrounding, intact femur), was sectioned transversely at one-centimeter intervals. Backscattered scanning electron microscopy was used to evaluate circumferentially the interface between the bone and the porous surface of each section. Bone ingrowth was considered to be present within a field when bone was in contact with the outermost layer of the sintered beads, it was detected within the porous space, and it had penetrated the porous space to a depth of at least one bead diameter. All eight components had some bone growth into the porous space. A mean of 35 per cent of the surface of the implants had bone ingrowth. In the areas where bone was present, 67 per cent of the available porous space on the extensively coated stems and 74 per cent on the proximally coated stems contained bone. With both types of implants, the greatest amount of compact bone ingrowth was found at the level where the porous coating ended. Transverse sections obtained at this level frequently demonstrated that bone ingrowth had occurred circumferentially and that the ingrowth was continuous with and an integral part of the femoral cortex. These direct connections to the cortex could be predicted from the appearance of the radiographs. In the most proximal transverse sections of both types of implants, bone was most frequently connected to the medial side and corners of the implant.(ABSTRACT TRUNCATED AT 250 WORDS)
Current Therapies for Chronic Hepatitis C (2010)

Hepatitis C virus affects more than 180 million people worldwide and as many as 4 million people in the United States. Given that most patients are asymptomatic until late in the disease progression, diagnostic screening and evaluation should be performed in patients who display high-risk behaviors associated with acquisition of hepatitis C. Chronic hepatitis C is associated with cirrhosis, hepatic failure, and death; therefore, treatment is aimed at reducing these complications, as well as improving quality of life and minimizing adverse effects. The American Association for the Study of Liver Diseases Practice Guidelines on the Diagnosis, Management, and Treatment of Hepatitis C represent the gold standard for guidance on the management of hepatitis C. Standard treatment for hepatitis C is peginterferon alpha in combination with ribavirin. Currently, two pegylated interferon products are approved by the U.S. Food and Drug Administration for the treatment of hepatitis C. The duration of therapy with peginterferon and ribavirin is dictated by viral genotype and virologic response. Additional therapies are under investigation for treatment of chronic hepatitis C and show early promise of comparative efficacy and fewer adverse effects. Special considerations in certain populations, including patients coinfected with human immunodeficiency virus, those with end-stage renal disease, injection drug users, pregnant women, and pediatric patients, should guide treatment decisions.
Wagner-Meerwein Rearrangement of Duocarmycins. (1996)

We found that treatment of the 8-O-protected-3-hydroxy derivatives of duocarmycin B2 (DUMB2, 1c) with camphorsulfonic acid (CSA) in toluene interestingly gave A-ring pyrrole analogs of DUMB2 (1c) in good yields. Their structures were unambiguously elucidated on the basis of NMR and mass spectrometry, and the mechanism was considered to be a Wagner-Meerwein type rearrangement. On the other hand, treatment of the 9-O-protected-3-hydroxy derivatives of duocarmycin B1 (1b) with CSA afforded different rearrangement products. In the case of bulky groups at the 9-O position, such as a tert-butyldimethylsilyl group, normal A-ring pyrrole analogs were obtained. Under the same condition, however, the 9-O-N, N-dimethylcarbamoyl-3-hydroxy compound of 1b gave a spiro compound, which was derived from a 1, 2-shift of the methoxycarbonyl group and a bonding between the C-8 position and the C-2' position. Compounds having a protective group of medium size gave a mixture of the normal rearrangement and the spiro derivative.
An antigen-targeted approach to adoptive transfer therapy of cancer. (1999)

Previous attempts to treat human malignancies by adoptive transfer of tumor-specific CTLs have been limited by the difficulty of isolating T cells of defined antigen specificity. The recent development of MHC class I/antigenic peptide tetrameric complexes that allow direct identification of antigen-specific T cells has opened new possibilities for the isolation and in vitro expansion of tumor-specific T cells. In the present study, we have derived polyclonal monospecific cell lines from circulating Melan-A-specific CTL precursors of HLA-A*0201+ melanoma patients by combining stimulation with recently identified peptide analogues of the immunodominant epitope from the melanoma-associated antigen Melan-A with staining with fluorescent HLA-A*0201/Melan-A peptide tetramers. In vitro expansion of antigen-specific CD8+ T cells was monitored by flow cytometry with the fluorescent tetramers and anti-CD8 monoclonal antibody. This analysis revealed that Melan-A 26-35 peptide analogues were much more efficient than the parental peptides in stimulating a rapid in vitro expansion of antigen-specific CD8+ T cells. These cells were then isolated by tetramer-guided cell sorting and subsequently expanded in vitro by mitogen stimulation. The resulting polyclonal but monospecific CTLs fully cross-recognized the parental peptides and were able to efficiently lyse Melan-A-expressing tumor cells. Altogether, these results pave the way to a molecularly defined approach to antigen-specific adoptive transfer therapy of cancer.
Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32 mutation confers resistance to HIV infection (2014)

Individuals homozygous for the C-C chemokine receptor type 5 gene with 32-bp deletions (CCR5Δ32) are resistant to HIV-1 infection. In this study, we generated induced pluripotent stem cells (iPSCs) homozygous for the naturally occurring CCR5Δ32 mutation through genome editing of wild-type iPSCs using a combination of transcription activator-like effector nucleases (TALENs) or RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 together with the piggyBac technology. Remarkably, TALENs or CRISPR-Cas9-mediated double-strand DNA breaks resulted in up to 100% targeting of the colonies on one allele of which biallelic targeting occurred at an average of 14% with TALENs and 33% with CRISPR. Excision of the piggyBac using transposase seamlessly reproduced exactly the naturally occurring CCR5Δ32 mutation without detectable exogenous sequences. We differentiated these modified iPSCs into monocytes/macrophages and demonstrated their resistance to HIV-1 challenge. We propose that this strategy may provide an approach toward a functional cure of HIV-1 infection.
Characterization of the human blood plasma proteome (2005)

We describe methods for broad characterization of the human plasma proteome. The combination of stepwise immunoglobulin G (IgG) and albumin protein depletion by affinity chromatography and ultrahigh-efficiency capillary liquid chromatography separations coupled to ion trap-tandem mass spectrometry enabled identification of 2392 proteins from a single plasma sample with an estimated confidence level of > 94%, and an additional 2198 proteins with an estimated confidence level of 80%. The relative abundances of the identified proteins span a range of over eight orders of magnitude in concentration (< 30 pg/mL to approximately 30 mg/mL), facilitated by the attomole-level sensitivity of the analysis methods. More than 80% of the observed proteins demonstrate interactions with IgG and/or albumin, and the human plasma protein loss in the affinity chromatography/strong cation exchange/reversed-phase liquid chromatography-tandem mass spectrometry methodology was investigated in detail. The results of this study provide a basis for a wide range of plasma proteomics studies, including broad quantitation of relative abundances in comparative studies of the identification of novel protein disease markers, as well as further studies of protein-protein interactions.
Modification of cefixime bioavailability by nifedipine in humans: involvement of the dipeptide carrier system (1992)

We studied the action of nifedipine on the bioavailability of cefixime, a molecule absorbed via the gut wall dipeptide carrier system in the rat, and on the bioavailability of D-xylose, which is absorbed via a pH (and Na(+)-)-dependent transporter. Each compound was administered alone or in combination with 20 mg of nifedipine to eight healthy male volunteers. Nifedipine significantly increased the absorption rate of cefixime (20.7 +/- 4.3 versus 16 +/- 3.5 mg/h in the absence of nifedipine). The absolute bioavailability of cefixime alone was 31% +/- 6% compared with 53% +/- 1% (P < 0.01) in the presence of nifedipine. The observed peak concentrations in serum were significantly different (2.5 +/- 0.3 mg/liter without nifedipine and 3.7 +/- 1.1 mg/liter with nifedipine; P < 0.02). In contrast, nifedipine induced no significant differences in the pharmacokinetic profile of xylose following oral administration. We conclude that (i) cefixime is absorbed in humans by an apparently active process which can be enhanced by a calcium channel blocker, in this case, nifedipine; and (ii) nifedipine does not modify the activity of the pentose transporter.
UV Electroluminescence Emission from ZnO Light‐Emitting Diodes Grown by High‐Temperature Radiofrequency Sputtering (2006)

A UV-light-emitting homojunction ZnO LED is grown by radiofrequency sputtering at high temperature, improving the structural, electrical, and optical properties of the n- and p-type ZnO layers. The figure shows a comparison of the electroluminescence spectra of A) a p–n homojunction ZnO LED and B) a ZnO LED with Mg0.1Zn0.9O layers used as energy barrier layers. Such materials are of interest for their potential use in long-lifetime solid-state lighting, high-density information storage, secure communication, and chemical/biological-agent monitoring.
Substructure similarity measurement in chinese recipes (2008)

Improving the precision of information retrieval has been a challenging issue on Chinese Web. As exemplified by Chinese recipes on the Web, it is not easy/natural for people to use keywords (e.g. recipe names) to search recipes, since the names can be literally so abstract that they do not bear much, if any, information on the underlying ingredients or cooking methods. In this paper, we investigate the underlying features of Chinese recipes, and based on workflow-like cooking procedures, we model recipes as graphs. We further propose a novel similarity measurement based on the frequent patterns, and devise an effective filtering algorithm to prune unrelated data so as to support efficient on-line searching. Benefiting from the characteristics of graphs, frequent common patterns can be mined from a cooking graph database. So in our prototype system called RecipeView, we extend the subgraph mining algorithm FSG to cooking graphs and combine it with our proposed similarity measurement, resulting in an approach that well caters for specific users' needs. Our initial experimental studies show that the filtering algorithm can efficiently prune unrelated cooking graphs without affecting the retrieval performance and the similarity measurement gets a relatively higher precision/recall against its counterparts.
Total and free prostate-specific antigen indexes in prostate cancer screening: value and limitation for Japanese populations (2006)

f/tPSA is more valuable compared with tPSA alone for the prediction of the occurrence of PCa. We recommend 0.250 as the cut-off value for f/tPSA in PCa screening for Asian men having so-called grey-zone tPSA.
Enantiomeric Propanolamines as selectiveN-Methyl-d-aspartate 2B Receptor Antagonists (2008)

Enantiomeric propanolamines have been identified as a new class of NR2B-selective NMDA receptor antagonists. The most effective agents are biaryl structures, synthesized in six steps with overall yields ranging from 11-64%. The compounds are potent and selective inhibitors of NR2B-containing recombinant NMDA receptors with IC 50 values between 30-100 nM. Potency is strongly controlled by substitution on both rings and the centrally located amine nitrogen. SAR analysis suggests that well-balanced polarity and chain-length factors provide the greatest inhibitory potency. Structural comparisons based on 3D shape analysis and electrostatic complementarity support this conclusion. The antagonists are neuroprotective in both in vitro and in vivo models of ischemic cell death. In addition, some compounds exhibit anticonvulsant properties. Unlike earlier generation NMDA receptor antagonists and some NR2B-selective antagonists, the present series of propanolamines does not cause increased locomotion in rodents. Thus, the NR2B-selective antagonists exhibit a range of therapeutically interesting properties.
Electrooptics: Phenomena, Materials And Applications (1994)

The Vast World of Electrooptics. Light Propagation in Anisotropic Media. Electrooptics: Concepts, Phenomena and Techniques. Electrooptics and Nonlinear Optics. Inorganic Electrooptic Materials. Organic Electrooptic Materials. Bulk Electrooptic Applications. Electrooptics and Integrated Optics. Semiconductor Quantum Wells and Superlattices. The Photorefractive Effect. Photorefractive Applications. Chapter References. Subject Index.
Small‐Molecule Inhibitors of the Hedgehog Signaling Pathway as Cancer Therapeutics (2010)

Inhibitors of the Hedgehog (Hh) molecular signaling pathway have emerged in recent years as a promising new class of potential therapeutics for cancer treatment. Numerous drug discovery efforts have resulted in the identification of a wide variety of small molecules that target different members of this pathway, including Smoothened (Smo), Sonic hedgehog protein (Shh), and Gli1. Several Smo inhibitors have now entered human clinical trials, and successful proof-of-concept studies have been carried out in patients with defined genetic mutations in the Hh pathway. This review provides a general overview of three main topics in this rapidly expanding area: 1) the various types of biological assays and in vivo models that have been employed for the identification and optimization of Hh pathway inhibitors; 2) Smo inhibitors reported to date, including recent clinical results where available; and 3) efforts toward the identification and characterization of inhibitors of other members of the Hh pathway.
Electroporation therapy: a new approach for the treatment of head and neck cancer (1999)

Electroporation can deliver exogenous molecules like drugs and genes into cells by pulsed electric fields through a temporary increase in cell membrane permeability. This effect is being used for the treatment of cancer by intratumoral injection of low dosage of an otherwise marginally effective chemotherapeutic drug, bleomycin. Application of a pulsed electric field results in substantially higher uptake of the drug and enhanced killing of the cancer cells than is possible by conventional methods. The MedPulser, a new treatment system for local electroporation therapy (EPT) of head and neck tumors was developed and is described in this paper. EPT with bleomycin has been found to be very effective in killing cancer cells in vitro, in mouse tumor xenografts in vivo, and in tumors in humans. Ten head and neck cancer patients with recurring or unresponsive tumors were enrolled in a Phase I/II clinical trial. Treatment of the entire tumor mass in each of eight patients resulted in five complete responses confirmed by biopsy and MRI, and three partial responses (> or = 50% shrinkage). Two additional patients who received partial treatment of their tumor mass had local response where treated, but no overall lesion remission. Duration of the complete responses ranges from 2-10 months to date. All patients tolerated the treatment well with no significant local or systemic adverse effects.
Structural analysis of p185c-neu and epidermal growth factor receptor tyrosine kinases: oligomerization of kinase domains. (1996)

The epidermal growth factor receptor (EGFR) and p185c-neu proteins associate as dimers to create an efficient signaling assembly. Overexpression of these receptors together enhances their intrinsic kinase activity and concomitantly results in oncogenic cellular transformation. The ectodomain is able to stabilize the dimer, whereas the kinase domain mediates biological activity. Here we analyze potential interactions of the cytoplasmic kinase domains of the EGFR and p185c-neu tyrosine kinases by homology molecular modeling. This analysis indicates that kinase domains can associate as dimers and, based on intermolecular interaction calculations, that heterodimer formation is favored over homodimers. The study also predicts that the self-autophosphorylation sites located within the kinase domains are not likely to interfere with tyrosine kinase activity, but may regulate the selection of substrates, thereby modulating signal transduction. In addition, the models suggest that the kinase domains of EGFR and p185c-neu can undergo higher order aggregation such as the formation of tetramers. Formation of tetrameric complexes may explain some of the experimentally observed features of their ligand affinity and hetero-receptor internalization.
T cell surface molecules regulating noncognate B lymphocyte activation. Role of CD2 and LFA-1 (1992)

A central event in humoral responses is the Ag-mediated interaction of Th cells and B cells. This interaction leads to the activation of both cell types and results in cytokine secretion by the T cells and proliferation and secretion of Ig by the B cells. The proliferative and differentiative responses of B cells are dependent on contact-mediated signals and cytokines provided by the activated Th cells. Although the role of cytokines in B cell activation and differentiation is understood, the nature of the signals delivered by the activated Th cells and the molecules involved in this process are not known. In this study we have examined Ag-mediated "cognate" T-B cell interactions as well as B cell activation induced by contact with preactivated and fixed Th lymphocytes. Our results indicate that both the T cell surface molecules lymphocyte function associated Ag-1 and CD2 are important in the activation of T cells by Ag presented by B lymphocytes. This indicates that B cells have similar characteristics as other APC. However, once the T cells are activated, contact-mediated stimulation of resting B lymphocytes (the noncognate phase) is dependent on CD2 but not lymphocyte function associated Ag-1. Two lines of evidence indicate this; first, it is inhibited by blocking of CD2 on the T cells and, second, such stimulation is not efficiently mediated by a CD2- Th cell line. Thus, CD2 plays an obligatory role at several discrete stages of T cell-mediated activation of resting B lymphocytes.
Regulation of Escherichia coli Phosphoenolpyruvate Carboxylase by Multiple Effectors In Vivo1: I. Estimation of the Activities in the Cells Grown on Various Compounds (1980)

Intracellular concentrations of phosphoenolpyruvate (PEP) and five kinds of allosteric effectors (acetyl-CoA, fructose 1,6-bisphosphate, GTP, L-aspartate, and L-malate) of PEP carboxylase were measured in E. coli cells grown on various compounds as a carbon source. Based on the data obtained, reaction systems which contained a definite concentration of the enzyme and the ligands at the concentrations found in vivo were constructed and the enzyme activities were measured. The ratio of each activity thus obtained to the maximal activity attainable with the same concentration of enzyme and saturating concentrations of the activators was estimated. For the cells grown on glucose, glycerol, or lactate, the extent of exhibition of the enzyme activity was 2-15% of the maximal activity. For the cells grown on acetate or oleate, the extent was 1-3%. For the cells grown on succinate, L-aspartate, L-malate, or glucose plus L-aspartate, the extent was less than 0.4%. Consideration of the data obtained in the present studies, together with those obtained in our previous studies on the enzyme level (Teraoka, H. et al. (1970) J. Biochem. 67, 567-575), showed that the control of the enzyme reaction in vivo is considerably different from that expected from the in vitro experiments, and that deficiencies of "coarse control" are covered by a "fine control."
Sutures and suture anchors: update 2003 (2003)

Screw anchors showed higher load to failure values than nonscrew designs, and the new biodegradable anchors showed failure loads lower than the anchors. All anchors were stronger than the suture for which they are designed.
Estrogen Prevents Glucocorticoid-Induced Apoptosis in Osteoblasts in Vivo and in Vitro (1999)

The ability of estrogen to prevent glucocorticoid-induced apoptosis in osteoblasts was studied both in vitro and in vivo. Glucocorticoid treatment for 72 h produced a dose-dependent increase in the number of apoptotic cells, determined by acridine orange/ethidium bromide staining, with a maximal response of 31 ± 2% and 26 ± 3% with 100 nm corticosterone in primary rat and mouse osteoblasts, respectively. Simultaneous administration of varying concentrations of 17β-estradiol and 100 nm corticosterone decreased apoptotic osteoblasts in a dose-dependent manner, with a maximal decrease of 70% with 0.01 nm 17β-estradiol. Terminal deoxynucleotidyltransferase-mediated deoxy-UTP-biotin nick end labeling also demonstrated glucocorticoid-induced DNA fragmentation that was inhibited by estrogen. Estrogen was shown to inhibit apoptosis induced by lipopolysaccharide treatment. As early as 6 h, Western blots demonstrated a dose-dependent decrease in the Bcl-2/Bax ratio, which reached a minimum of 0.18 in osteoblasts treated with 1000 nm corticosterone for 72 h. This reduction in Bcl-2/Bax was abolished by treating osteoblasts simultaneously with 17β-estradiol, but not with 17α-estradiol. In 7-day-old mice, administration of varying concentrations of dexamethasone for 72 h resulted in a dose-dependent increase in the number of apoptotic osteoblasts as demonstrated by in situ terminal deoxynucleotidyltransferase-mediated deoxy-UTP-biotin nick end labeling staining of calvaria. A maximum of 22 ± 1% apoptotic osteoblasts on the bone surface was found with 1 mg/kg BW dexamethasone compared with 2 ± 1% in vehicle-treated mice. Injection of varying concentrations of 17β-estradiol (0.5–5 mg/kg BW), but not 17α-estradiol, with 1 mg/kg dexamethasone produced a dose-dependent decrease in the number of apoptotic osteoblasts to 5 ± 1% with 5 mg/kg 17β-estradiol. Thus, glucocorticoid-induced apoptosis of osteoblasts may be prevented at least in part by 17β-estradiol.