gebhart/patrepeval huggingface dataset:
Adalimumab in Crohn's disease. (2007)

Although the advent of infliximab has changed the treatment paradigm and goals in inflammatory bowel diseases (IBD), it does not provide a cure for IBD and recent evidence has demonstrated that the immunogenicity of this chimeric anti-TNF antibody is associated with secondary loss of response and intolerance. In ulcerative colitis (UC) the efficacy of infliximab was demonstrated in two large clinical trials, but long-term maintenance efficacy data are lacking. Novel biological agents have entered clinical development and pioneering trials have been reported in the last two years. For Crohn's disease (CD) two anti-TNF agents, the fully human IgG1 anti-TNF monoclonal adalimumab and the humanized pegylated Fab-fragment certolizumab-pegol and the humanized anti alpha4 integrin IgG4 antibody both have demonstrated efficacy as maintenance agents. Adalimumab has been approved to treat active rheumatoid arthritis, psoriatric arthritis, and ankylosing spondylitis, and recently moderate-to-severe luminal CD has been added as an indication for this agent both by the FDA and EMEA. Further evidence is needed to establish the therapeutic potential of adalimumab in fistulizing CD and in UC. The benefit to risk ratio of anti-TNF agents in refractory IBD is clearly positive and since most of the toxicity is class specific, adalimumab is expected to have a safety profile similar to that of infliximab except for adverse events related to infusions.
Hormone replacement therapy and the risk of epithelial ovarian carcinoma: a meta-analysis (1998)

Prolonged use of hormone therapy by postmenopausal women may be associated with an increased risk of developing epithelial carcinoma of the ovary.
Hot Data Identification for Flash Memory Using Multiple Bloom Filters (2010)

Hot data identification can be applied to a variety of fields. Particularly in flash memory, it has a critical impact on its performance (due to garbage collection) as well as its lifespan (due to wear leveling). Although this is an issue of paramount importance in flash memory, it is the least investigated one. Moreover, all existing schemes focus only or mainly on a frequency viewpoint. However, recency factor also must be considered as much importantly as the frequency for hot data identification. In this paper, we propose a novel hot data identification scheme adopting multiple bloom filters to efficiently capture finer-grained recency as well as frequency. In addition to this scheme, we propose a window-based direct address counting (named WDAC) algorithm to approximate an ideal hot data identification as our baseline. Unlike the existing baseline algorithm that cannot appropriately capture recency information due to its exponential batch decay, our WDAC algorithm using a sliding window concept can capture very fine-grained recency information. Our experimental evaluation with diverse realistic workloads including real SSD traces demonstrates that our proposed scheme outperforms the state-of-the-art hot data identification scheme. In particular, our scheme not only consumes less memory (50% less) and requires less computational overhead up to 58%, but also improves its performance up to 65%.
Identification of integrated hepatitis B virus DNA sequences in human hepatocellular carcinomas (1981)

DNA extracts from hepatocellular carcinomas of 13 patients from South Africa were examined for hepatitis B virus (HBV) DNA sequences by molecular hybridization using [32P]-labeled recombinant, cloned, and purified HBV-DNA. Eight patients were HBV carriers as demonstrated by the presence of hepatitis B surface antigen (HBsAg) in their serum, and each of these patients and HBV-DNA sequences in hepatocellular carcinoma tissue. Five patients who were not HBsAg carriers, did not have HBV-DNA in their tumors. In DNA extracts from all tumors of patients who were HBsAg-positive, the HBV-DNA was integrated into the host genome. The integration pattern was unique for each tumor, but HBV-DNA bands of a given length were present in more than one specimen and in a human hepatocellular carcinoma cell line (PLC/PRF/5). These results suggest that integration of HBV-DNA into the human genome occurs in conjunction with malignant transformation.
Identification of hepatitis C viruses with a nonconserved sequence of the 5' untranslated region (1992)

The nucleotide sequence of the 5' untranslated region of hepatitis C virus (HCV) has been shown to be conserved. In contrast, we have detected more sequence variation in this region in several HCV isolates than hitherto expected. The nucleotide sequences of the 5' untranslated regions of these isolates differ significantly from that of the prototype but are very similar to each other. We believe that these isolates belong to the same type of HCV. Among 240 HCV RNA polymerase chain reaction-positive specimens that we examined, 7 belong to this type. The results suggest that the HCV variants that we detected represent a different type of HCV and that they are responsible for approximately 3% of HCV infections in patients that we have examined.
MR Imaging Relaxation Times of Abdominal and Pelvic Tissues Measured in Vivo at 3.0 T: Preliminary Results (2004)

T1 relaxation times are generally higher and T2 relaxation times are generally lower at 3.0 T than at 1.5 T, but the magnitude of change varies greatly in different tissues.
Kallikreins are involved in an miRNA network that contributes to prostate cancer progression (2014)

MicroRNAs (miRNAs) are short RNA nucleotides that negatively regulate their target genes. They are differentially expressed in prostate cancer. Kallikreins are genes that encode serine proteases and are dysregulated in cancer. We elucidated a miRNA-kallikrein network that can be involved in prostate cancer progression. Target prediction identified 23 miRNAs that are dysregulated between high and low risk biochemical failure and are predicted to target five kallikreins linked to prostate cancer; KLK2, KLK3, KLK4, KLK14 and KLK15. We also identified 14 miRNAs that are differentially expressed between Gleason grades and are predicted to target these kallikreins. This demonstrates that kallikreins are downstream effectors through which miRNAs influence tumor progression. We show, through in-silico and experimental analysis, that miR-378/422a and its gene targets PIK3CG, GRB2, AKT3, KLK4 and KLK14 form an integrated circuit in prostate cancer. Our analysis shows that a minisatellite sequence in the kallikrein locus consists of a number of microsatellite repeats that represent predicted miRNA response elements. A number of kallikrein and non-kallikrein prostate cancer-related genes share these microsatellite repeats. We validated some of these interactions in prostate cancer cell lines. Finally, we provide preliminary evidence on the presence of a miRNA-mediated cross-talk between kallikreins, including a kallikrein pseudogene.
Directing Oleate Stabilized Nanosized Silver Colloids into Organic Phases (1998)

Nanosized hydrophobic, oleate stabilized silver organosols in various organic solvents are obtained using a solvent exchange method. The silver particles are initially prepared as a hydrosol in the presence of sodium oleate (surfactant). Then a transfer of the colloid to an organic phase is induced by a low concentration of several agents such as orthophosphoric acid, with a transfer efficiency of 50−70%. The hydrophobic colloid is stable and the particles retain their integrity even after the solvent is evaporated and the dried deposit is resuspended in a variety of other solvents. We present the preparation method in detail and characterize the hydrosol and organosol particles by electron microscopy, electrophoresis, and UV−visible extinction spectroscopy. On the basis of IR spectroscopy we discuss the conformation of the surfactant adsorbed on the silver cores and the changes in it as the particles transfer into the organic environment.
1-[1-[4-[(N-Acetyl-4-piperidinyl)oxy]-2- methoxybenzoyl]piperidin-4-yl]-4H-3,1- benzoxazin-2(1H)-one (L-371,257): a new, orally bioavailable, non-peptide oxytocin antagonist. (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1-[1-[4-[(N-Acetyl-4-piperidinyl)oxy]-2- methoxybenzoyl]piperidin-4-yl]-4H-3,1- benzoxazin-2(1H)-one (L-371,257): a new, orally bioavailable, non-peptide oxytocin antagonist.Peter D. Williams, Bradley V. Clineschmidt, Jill M. Erb, Roger M. Freidinger, Maribeth T. Guidotti, Edward V. Lis, Joseph M. Pawluczyk, Douglas J. Pettibone, Duane R. Reiss, and Cite this: J. Med. Chem. 1995, 38, 23, 4634–4636Publication Date (Print):November 1, 1995Publication History Published online1 May 2002Published inissue 1 November 1995https://pubs.acs.org/doi/10.1021/jm00023a002https://doi.org/10.1021/jm00023a002research-articleACS PublicationsRequest reuse permissionsArticle Views415Altmetric-Citations49LEARN 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
Determination of inflammatory bowel disease activity by breath pentane analysis (1993)

We have previously demonstrated the correlation of breath pentane with gross and histologic evidence of intestinal inflammation in a rodent colitis model. This current study also demonstrates that pentane analysis can be correlated with inflammatory bowel disease activity in humans.
Abstract 1601: Hsp90 inhibition results in a significant delay in tumor progression in a model of emerging EGFR TKI resistance in non-small cell lung cancer (2011)

Abstract Heat shock protein 90 (Hsp90) plays a role in regulating the stability of key cancer-causing proteins through its role as a protein chaperone. Proteins chaperoned by Hsp90, known as client proteins, include cancer-causing forms of ALK, BCR-ABL, EGFR, FLT3 and HER2. Infinity is developing two drug candidates in its Hsp90 chaperone inhibitor program: IPI-504 (retaspimycin hydrochloride), an intravenously-administered small molecule, and IPI-493, which is administered orally. EGFR tyrosine kinase inhibitors (TKIs) are an effective treatment for lung cancer patients with activating mutations in EGFR. After a dramatic initial response, however, most patients become resistant to drug treatment and progress. In about half of these cases, resistance is due to a second point mutation in EGFR (T790M). It is believed that in at least some of these cases, the TKI resistance mutations are pre-existing and that treatment with TKIs selects for the resistant cells. In an effort to model the emergence of resistance to TKIs from pre-existing mutations, we developed a novel in vivo model, where gefitinib treatment initially leads to tumor regression followed by rebound of tumor growth and outgrowth of drug resistant clones containing the T790M mutation. We show that in this model, treatment with IPI-493 alone and IPI-493 following gefitinib resulted in tumor growth inhibition of 61 and 77%, respectively, when compared with gefitinib treatment alone. Treatment with IPI-493 alone also resulted in a significant delay in time to tumor progression with ∼40% of animals still on study 45 days following tumor implant; all animals treated with either vehicle or gefitinib had been removed due to tumor progression. Interestingly, treatment with IPI-493 following gefitinib resulted in an even more impressive delay in time to progression, with &amp;gt;50% of animals still on study on day 65 post-implant. These results suggest that further studies with Hsp90 inhibitors in EGFR mutant NSCLC patients who have been pre-treated with a TKI may be warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1601. doi:10.1158/1538-7445.AM2011-1601
Space closure with loop mechanics for treatment of bimaxillary protrusion: a case report. (2015)

This case report intends to highlight the space closure with tear drop loop mechanics for bimaxillary protrusion. Loops can be fabricated in a sectional or full arch wire, and closing loops are usually used in loop mechanics for extraction space closure. The major advantage of loop mechanics is the lack of friction between the bracket and arch wire during space closure. An adult patient with bimaxillary protrusion reported to the clinic. The patient was treated successfully by maximum retraction of maxillary and mandibular anterior teeth after extraction of all first premolars. Space closure was begun using a moment differential between posterior and anterior segments created by a Tear drop loop. Anterior teeth were moved with bodily movement, and no anchorage loss of the posterior segments was seen using a Tear drop loop spring. A stable result with normal over jet and overbite was achieved with retraction of maxillary and mandibular anterior teeth. With a Tear drop loop, individual biomechanical responses can be achieved, and it is possible to calculate force magnitude for every patient.
Small Interfering RNA for Effective Cancer Therapies (2011)

Small interfering RNA (siRNA) has become a specific and powerful tool to turn off the expression of target genes, and has turned into a promising tool in molecular medicine. It can be targeted against cancer by several strategies. These include the suppression of overexpressed oncogenes, retarding cell division by interfering with cyclins and related genes or enhancing apoptosis by inhibiting anti-apoptotic genes. RNA interference (RNAi) against multidrug resistance (MDR) genes or chemo/radio-resistance and angiogenesis targets may also provide beneficial cancer treatments. Successful cancer therapy by siRNA in vitro and in vivo provides the enthusiasm for potential therapeutic applications of this technique. Here, we review RNAi in cancer therapy, highlighting recent progress and examining the hurdles that must be overcome before this promising technology is ready for clinical use.
Specific marrow ablation before marrow transplantation using an aminophosphonic acid conjugate 166Ho-EDTMP (1992)

166Holmium ethylenediaminetetramethylene phosphonic acid (166Ho-EDTMP) is a short-lived beta-emitting radionuclide complexed to an aminophosphonate ligand that we have investigated in a canine model as a potential agent for specific marrow ablation before marrow transplantation. After intravenous injections, 166Ho-EDTMP distributed principally to bone and after 24 hours the concentrations of 166Ho- EDTMP in bone were more than 200-fold higher than in any other organ. Increasing dosages of 166Ho-EDTMP led to increasingly prolonged and severe myelosuppression, but myeloablation was not achieved. Histologic examination of recovering animals suggested that the spleen may have acted as a reservoir for circulatory hematopoietic precursors. Four splenectomized animals administered 20 to 30 mCi/kg 166Ho-EDTMP without marrow transplantation died with marrow aplasia, while four splenectomized animals administered similar dosages of 166Ho-EDTMP followed by autologous transplantation recovered. The dose-limiting toxicity of 166Ho-EDTMP appeared to be marrow stromal damage resulting in myelofibrosis, which was reversible. These results suggest that 166Ho-EDTMP can be used to specifically ablate marrow function before marrow transplantation.
Functional Expression of Arabidopsis thaliana Anthranilate Synthase Subunit I in Escherichia coli (1994)

Anthranilate synthase is involved in tryptophan (Trp) biosynthesis. Functional expression of subunit I from Arabidopsis (ASA1) was achieved in bacteria as a protein fused with glutathione S-transferase (GST). The active product was purified in a single step on a glutathione-Sepharose column. The Vmax (45 nmol min-1mg-1), the apparent K(M) for chorismate (180 microM), and the feedback inhibition by Trp (complete inhibition by 10 microM Trp) of the purified fusion product (GST-ASA1) were comparable to anthranilate synthase purified from plants. Polyclonal antibodies raised against the fusion project and purified by affinity chromatography on a GST-ASA1-Sepharose column cross-reacted with a 61.5-kD protein in a partially purified anthranilate synthase preparation from corn seedlings. GST-ASA1 cleavage by thrombin, as well as site-directed mutagenesis modifications of the Trp allosteric site, inactivated the recombinant protein.
Continuous ultrasonic hydrogenation of soybean oil. II. Operating conditions and oil quality (1987)

Abstract In previous work we found that ultrasonic energy greatly enhanced the rate of hydrogenation of soybean oil. We have now investigated parameters of ultrasonic hydrogenation and the quality of the resulting products. Refined and bleached soybean oil was hydrogenated continuously with and without ultrasonic energy at different temperatures, pressures and catalyst concentrations. Flavor and oxidative stability of the oils were compared with a commercially hydrogenated soybean oil. The extent of hydrogenation (ΔIV) was not affected by temperature between 245 and 290 C, but was greater at 106 psig than at 65 psig hydrogen pressure. The ΔIV of hydrogenated oils increased linearly with catalyst concentration from 40 ppm to 150 ppm nickel. At the same catalyst concentration the IV drop was significantly increased when ultrasonic energy was used. By reducing the amount of power supplied to the ultrasonic reactor to 40% of full power, the specific power (watts/ΔIV) was lowered by 60%. Linolenate selectivities and specific isomerization (% trans /ΔIV) remained the same, but linoleate selectivities were lower than for batch hydrogenation under varied operating parameters. Flavor scores were not significantly different, initially or after storage eight days at 60 C, for oils continuously hydrogenated with and without ultrasonic energy. Hydrogenation of soybean oil with ultrasonic energy offers a method to produce good quality products at potentially lower cost than present methods.
Fabrication and Characterization of Magnetic Microrobots for Three‐Dimensional Cell Culture and Targeted Transportation (2013)

Magnetically manipulated microrobots are demonstrated for targeted cell transportation. Full three-dimensional (3D) porous structures are fabricated with an SU-8 photoresist using a 3D laser lithography system. Nickel and titanium are deposited as a magnetic material and biocompatible material, respectively. The fabricated microrobots are controlled in the fluid by external magnetic fields. Human embryonic kidney 239 (HEK 239) cells are cultivated in the microrobot to show the possibility for targeted cell transportation.
New Cyclic Peptides from the AscidianLissoclinumpatella (1998)

Four new cyclic peptides, patellamide G (2) and ulithiacyclamides E-G (3-5), along with the known patellamides A-C (6-8) and ulithiacyclamide B (9), were isolated from the ascidian Lissoclinum patella collected in Pohnpei, Federated States of Micronesia. The planar structures of these peptides were determined from 1D and 2D 1H and 13C NMR spectra. The absolute stereochemistries of the amino acid units, except for cysteine, were assigned by chiral GC analysis of N(O)-trifluoroacetyl isopropyl ester derivatives of amino acids obtained by acid hydrolysis of the intact and ozonized peptides. The structures of ulithiacyclamides E-G (3-5) were confirmed by chemical conversion. Patellamides B (7) and C (8) exhibited in vitro modulation of multidrug resistance in CEM/VBL100 cells.
Role of group-conserved residues in the helical core of β 2 -adrenergic receptor (2007)

G protein-coupled receptors (GPCRs) belonging to class A contain several highly conserved (>90%) amino acids in their transmembrane helices. Results of mutational studies of these highly conserved residues suggest a common mechanism for locking GPCRs in an inactive conformation and for their subsequent activation upon ligand binding. Recently, a second set of sites in the transmembrane helices has been identified in which amino acids with small side chains, such as Gly, Ala, Ser, Thr, and Cys, are highly conserved (>90%) when considered as a group. These group-conserved residues have not been recognized as having essential structural or functional roles. To determine the role of group-conserved residues in the beta(2)-adrenergic receptor (beta(2)-AR), amino acid replacements guided by molecular modeling were carried out at key positions in transmembrane helices H2-H4. The most significant changes in receptor expression and activity were observed upon replacement of the amino acids Ser-161 and Ser-165 in H4. Substitution at these sites by larger residues lowered the expression and activity of the receptor but did not affect specific binding to the antagonist ligand dihydroalprenolol. A second site mutation, V114A, rescued the low expression of the S165V mutant. Substitution of other group-conserved residues in H2-H4 by larger amino acids lowered receptor activity in the order Ala-128, Ala-76, Ser-120, and Ala-78. Together these data provide comprehensive analysis of group-conserved residues in a class A GPCR and allow insights into the roles of these residues in GPCR structure and function.
Synthesis and Properties of Novel Tetraalkyl Cationic Lipids (2002)

The synthesis, physical properties, and transfection potencies of two representives of a new class of divalent, tetraalkyl cationic lipids is described. These cationic lipids are dimers of N,N-Dioleyl-N,N-dimethylammonium chloride (DODAC) joined by a hydrocarbon tether three or six carbons in length (TODMAC3 and TODMAC6, respectively). It is shown that TODMAC6 can display improved transfection properties in comparison to DODAC when formulated into plasmid DNA-cationic lipid complexes. These improved transfection potencies are observed at cationic lipid to DNA charge ratios of two or higher. It is also shown that TODMAC6 exhibits equivalent or improved ability (as compared to DODAC) to induce nonbilayer structure in mixtures with anionic lipid. This is consistent with the hypothesis that the ability of cationic lipids to induce nonbilayer structures when mixed with anionic lipids is correlated to their transfection potency. Complexes containing TODMAC3 on the other hand exhibit lower transfection potencies than achieved with DODAC, behavior that is consistent with steric effects limiting the formation of ion pairs with anionic lipids. It is concluded that TODMAC6 exhibits potential as a transfection agent for in vitro and in vivo use and that the design of cationic lipids according to their ability to induce nonbilayer structure provides a useful guide for synthesis of new cationic lipids.