gebhart/patrepeval huggingface dataset:
Flap Endonuclease Disengages Dna2 Helicase/Nuclease from Okazaki Fragment Flaps (2006)

Okazaki fragments contain an initiator RNA/DNA primer that must be removed before the fragments are joined. In eukaryotes, the primer region is raised into a flap by the strand displacement activity of DNA polymerase delta. The Dna2 helicase/nuclease and then flap endonuclease 1 (FEN1) are proposed to act sequentially in flap removal. Dna2 and FEN1 both employ a tracking mechanism to enter the flap 5' end and move toward the base for cleavage. In the current model, Dna2 must enter first, but FEN1 makes the final cut at the flap base, raising the issue of how FEN1 passes the Dna2. To address this, nuclease-inactive Dna2 was incubated with a DNA flap substrate and found to bind with high affinity. FEN1 was then added, and surprisingly, there was little inhibition of FEN1 cleavage activity. FEN1 was later shown, by gel shift analysis, to remove the wild type Dna2 from the flap. RNA can be cleaved by FEN1 but not by Dna2. Pre-bound wild type Dna2 was shown to bind an RNA flap but not inhibit subsequent FEN1 cleavage. These results indicate that there is a novel interaction between the two proteins in which FEN1 disengages the Dna2 tracking mechanism. This interaction is consistent with the idea that the two proteins have evolved a special ability to cooperate in Okazaki fragment processing.
ChemInform Abstract: Indoles, Indolenines, and Indolines. Part 5. Diastereoselective Spirocyclization of C‐(Alkyloxycarbonyl)formimines of 2‐Substituted 1H‐Indole‐3‐ethanamides (= Tryptamines): Basic Studies. (1990)

Abstract The title cyclization leads to compounds such as (Va), (Vb) (space group P2 1 with Z=2), (VII) (space group P2 1 2 1 2 1 with Z=4) and (IX) which represent a spirocyclic partial structure found in many indole alkaloids.
Low-Complexity Intra Prediction Refinements for Video Coding (2018)

In existing video coding standards such as H.264/AVC and HEVC, the intra prediction is typically derived using fixed, symmetric prediction filters along the prediction direction, e.g., in planar mode, top-right and bottom-left samples are predicted using symmetric prediction filters. However, in case of asymmetric availability of neighboring reference samples, the performance of intra prediction filters designed in HEVC may not be optimal. To further refine the intra prediction and achieve higher accuracy of prediction samples, this paper proposes low-complexity refinements over HEVC intra prediction, which are applied on frequently used planar, DC, horizontal and vertical modes. The proposed method only requires simple addition and bit-shift operations on top of HEVC's intra prediction implementation. Experimental results show that, an average of 0.7% coding gain is achieved for intra coding with no increase in run-time complexity.
Janus Activated Kinase inhibition in Myelofibrosis (2012)

Janus Activated Kinase (JAK) 2 plays an important role in the pathogenesis of myelofibrosis (MF). Ruxolitinib (INCB018424, Jakafi) is a potent dual JAK1 and JAK2 inhibitor. In November 2011, it became approved by the US FDA for the treatment of intermediate or high-risk MF. This review shall outline the role of Ruxolitinib in the current management of MF and its potential future.
Genetic analysis of benign, low-grade, and high-grade ovarian tumors. (1995)

Genetic abnormalities were assessed in 56 benign, low-, and high-grade ovarian tumors using comparative genomic hybridization (CGH) and analysis of loss of heterozygosity (LOH). In addition, 95 epithelial tumors were analyzed for microsatellite repeat instability. DNA sequence copy number abnormalities (CNAs) were not detected in the benign tumors, and more were detected in high-grade than in low-grade cancers. Almost no microsatellite repeat instability was detected in these cancers. CNAs occurring in more than 30% of the cancers included increased copy number on 3q25-26 and 8q24 and reduced copy number on 16q and 17pter-q21. Another 14 CNAs occurred in more than 20% of the cancers. Increased copy number at 3q25-26 and 20q13 was the most frequent CNA in low-grade tumors, and increased copy number at 8q24 occurred preferentially in high-grade tumors. The presence of a large number of CNAs per tumor was significantly correlated with reduced patient survival duration. Reduced copy number on 17pter-q21 was most strongly associated with accumulation of a large number of CNAs. The overall concordance between LOH and reduced copy number detected by CGH was 84%, but only 31% of the LOH was associated with reduced copy number detected using CGH.
Role of Exogenous and Endogenous Trophic Factors in the Regulation of Extraocular Muscle Strength during Development (2004)

Endogenous trophic factors regulate and/or maintain extraocular muscle force through a rapid mechanism that appears to involve changes in muscle mass and specifically enlargement of muscle fiber diameters. CT-1 and IGF-I may be considered promising candidate trophic factors for therapeutic strengthening of eye muscles in the developing extraocular muscle system.
Endoplasmic Reticulum Retention, Degradation, and Aggregation of Olfactory G‐Protein Coupled Receptors (2003)

The mammalian olfactory G-protein coupled receptor family is comprised of hundreds of proteins that mediate odorant binding and initiate signal transduction cascades leading to the sensation of smell. However, efforts to functionally express olfactory receptors and identify specific odorant ligand-olfactory receptor interactions have been severely impeded by poor olfactory receptor surface expression in heterologous systems. Therefore, experiments were performed to elucidate the cellular mechanism(s) responsible for inefficient olfactory receptor cell surface expression. We determined that the mouse odorant receptors mI7 and mOREG are not selected for export from the ER and therefore are not detectable at the Golgi apparatus or plasma membrane. Specifically, olfactory receptors interact with the ER chaperone calnexin, are excluded from ER export sites, do not accumulate in ER-Golgi transport intermediates at 15 degrees C, and contain endoglycosidase H-sensitive oligosaccharides, consistent with olfactory receptor exclusion from post-ER compartments. A labile pool of ER-retained olfactory receptors are post-translationally modified by polyubiquitination and targeted for degradation by the proteasome. In addition, olfactory receptors are sequestered into ER aggregates that are degraded by autophagy. Collectively, these data demonstrate that poor surface expression of olfactory receptors in heterologous cells is attributable to a combination of ER retention due to inefficient folding and poor coupling to ER export machinery, aggregation, and degradation via both proteasomal and autophagic pathways.
Simulation performance of a blind adaptive array for a realistic mobile channel (2002)

A least squares constant modulus algorithm (LSCMA) is used to blindly adapt a narrowband beamformer to capture a Doppler-shifted and fading binary phase shift keying (BPSK) signal corrupted by noise and multipath. The multipath components are modeled as having equal amplitude and uniformly distributed phase, as well as directions of arrival in three dimensions (the Parsons and Turkmani channel model). Two implementations of the LSCMA are evaluated by computer simulation for a 4-element antenna array moving at 60 mph and 120 mph in noisy environments. In a comparison of bit error rates (BERs) between the two LSCMA implementations and the single antenna, the LSCMAs are found to provide 8 to 9 dB improvement in the link budget for a BER of 1%.
Preclinical Antitumor Activity of Cabazitaxel, a Semisynthetic Taxane Active in Taxane-Resistant Tumors (2013)

Cabazitaxel is as active as docetaxel in docetaxel-sensitive tumor models but is more potent than docetaxel in tumor models with innate or acquired resistance to taxanes and other chemotherapies. These studies were the basis for subsequent clinical evaluation.
Hydroxyurea-Stalled Replication Forks Become Progressively Inactivated and Require Two Different RAD51-Mediated Pathways for Restart and Repair (2010)

Faithful DNA replication is essential to all life. Hydroxyurea (HU) depletes the cells of dNTPs, which initially results in stalled replication forks that, after prolonged treatment, collapse into DSBs. Here, we report that stalled replication forks are efficiently restarted in a RAD51-dependent process that does not trigger homologous recombination (HR). The XRCC3 protein, which is required for RAD51 foci formation, is also required for replication restart of HU-stalled forks, suggesting that RAD51-mediated strand invasion supports fork restart. In contrast, replication forks collapsed by prolonged replication blocks do not restart, and global replication is rescued by new origin firing. We find that RAD51-dependent HR is triggered for repair of collapsed replication forks, without apparent restart. In conclusion, our data suggest that restart of stalled replication forks and HR repair of collapsed replication forks require two distinct RAD51-mediated pathways.
Introduction of 9-fluorenylmethyloxycarbonyl, trichloroethoxycarbonyl, and benzyloxycarbonyl amine protecting groups into O-unprotected hydroxyamino acids using succinimidyl carbonates (1982)

9-Fluorenylmethyl succinimidyl, pentachlorophenyl, and benzotriazole-1-yl carbonates were prepared and their reactivity with L-serine and L-serine benzyl ester was compared. The most efficient reagent, 9-fluorenylmethyl succinimidyl carbonate, was used for the preparation of 9-fluorenylmethyloxycarbonyl derivatives of other hydroxyamino acids and hydroxyamino acid esters in high yields. The use of trichloroethyl and benzyl succinimidyl carbonates for an efficient conversion of hydroxyamino acids and their esters into the corresponding N-trichloroethoxycarbonyl and benzyloxycarbonyl derivatives is described.
A framework to analyze multiple time series data: A case study with Streptomyces coelicolor (2005)

Transcriptional regulation in differentiating microorganisms is highly dynamic involving multiple and interwinding circuits consisted of many regulatory genes. Elucidation of these networks may provide the key to harness the full capacity of many organisms that produce natural products. A powerful tool evolved in the past decade is global transcriptional study of mutants in which one or more key regulatory genes of interest have been deleted. To study regulatory mutants of Streptomyces coelicolor, we developed a framework of systematic analysis of gene expression dynamics. Instead of pair-wise comparison of samples in different combinations, genomic DNA was used as a common reference for all samples in microarray assays, thus, enabling direct comparison of gene transcription dynamics across different isogenic mutants. As growth and various differentiation events may unfold at different rates in different mutants, the global transcription profiles of each mutant were first aligned computationally to those of the wild type, with respect to the corresponding growth and differentiation stages, prior to identification of kinetically differentially expressed genes. The genome scale transcriptome data from wild type and a DeltaabsA1 mutant of Streptomyces coelicolor were analyzed within this framework, and the regulatory elements affected by the gene knockout were identified. This methodology should find general applications in the analysis of other mutants in our repertoire and in other biological systems.
STRUCTURE AND FUNCTION OF G PROTEIN-COUPLED RECEPTORS (1994)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Immunosignature system for diagnosis of cancer (2014)

Although the search for disease biomarkers continues, the clinical return has thus far been disappointing. The complexity of the body's response to disease makes it difficult to represent this response with only a few biomarkers, particularly when many are present at low levels. An alternative to the typical reductionist biomarker paradigm is an assay we call an "immunosignature." This approach leverages the response of antibodies to disease-related changes, as well as the inherent signal amplification associated with antigen-stimulated B-cell proliferation. To perform an immunosignature assay, the antibodies in diluted blood are incubated with a microarray of thousands of random sequence peptides. The pattern of binding to these peptides is the immunosignature. Because the peptide sequences are completely random, the assay is effectively disease-agnostic, potentially providing a comprehensive diagnostic on multiple diseases simultaneously. To explore the ability of an immunosignature to detect and identify multiple diseases simultaneously, 20 samples from each of five cancer cohorts collected from multiple sites and 20 noncancer samples (120 total) were used as a training set to develop a reference immunosignature. A blinded evaluation of 120 blinded samples covering the same diseases gave 95% classification accuracy. To investigate the breadth of the approach and test sensitivity to biological diversity further, immunosignatures of >1,500 historical samples comprising 14 different diseases were examined by training with 75% of the samples and testing the remaining 25%. The average accuracy was >98%. These results demonstrate the potential power of the immunosignature approach in the accurate, simultaneous classification of disease.
Optimal Selection for Direct Mail (1995)

Direct marketing (mail) is a growing area of marketing practice, yet the academic journals contain very little research on this topic. The most important issue for direct marketers is how to sample targets from a population for a direct mail campaign. Although some selection methods are described in the literature, there seems to be not a single paper discussing the analytical and statistical aspects involved. The objective of this paper is to introduce a comprehensive methodology for the selection of targets from a mailing list for direct mail. At least theoretically, this methodology leads to more efficient selection procedures than the existing ones. The latter are not based on an optimal selection strategy, whereas we explicitly take the profit function into account. By equating marginal costs and marginal returns we determine which households should receive a mailing in order to maximize expected profit. In the empirical part we show that our methodology has great predictive accuracy and generates higher net returns than traditional approaches.
Epithelial Phenotype Confers Resistance of Ovarian Cancer Cells to Oncolytic Adenoviruses (2009)

We studied the susceptibility of primary ovarian cancer cells to oncolytic adenoviruses. Using gene expression profiling of cancer cells either resistant or susceptible to viral oncolysis, we discovered that the epithelial phenotype of ovarian cancer represents a barrier to infection by commonly used oncolytic adenoviruses targeted to coxsackie-adenovirus receptor or CD46. Specifically, we found that these adenovirus receptors were trapped in tight junctions and not accessible for virus binding. Accessibility to viral receptors was critically linked to depolarization and the loss of tight and adherens junctions, both hallmarks of epithelial-to-mesenchymal transition (EMT). We showed that specific, thus far little-explored adenovirus serotypes (Ad3, Ad7, Ad11, and Ad14) that use receptor(s) other than coxsackie-adenovirus receptor and CD46 were able to trigger EMT in epithelial ovarian cancer cells and cause efficient oncolysis. Our studies on ovarian cancer cultures and xenografts also revealed several interesting cancer cell biology features. Tumors in situ as well as tumor xenografts in mice mostly contained epithelial cells and cells that were in a hybrid stage where they expressed both epithelial and mesenchymal markers (epithelial/mesenchymal cells). These epithelial/mesenchymal cells are the only xenograft-derived cells that can be cultured and with passaging undergo EMT and differentiate into mesenchymal cells. Our study provides a venue for improved virotherapy of cancer as well as new insights into cancer cell biology.
Multidisciplinary approaches to address food insecurity and nutrition among youth and their families (2015)

Our aim in publishing this issue of JARC on nutrition and food insecurity is to understand the factors associated with nutrition and food insecurity in the U.S. and around the world; to elucidate the potential consequences of food insecurity on physical and mental health; and to raise awareness and identify solutions to address this complex issue. We also aim to encourage collaboration across disciplines in order to frame initiatives that reduce these threats to child health, well-being and success.
BIODEGRADABLE ELASTOMERIC BIOMATERIALS — POLYETHYLENE OXIDE/POLYETHYLENE TEREPHTHALATE COPOLYMERS (1977)

I.C.I./University of Liverpool Joint Laboratory, Bio-Engineering Unit, Liverpool, England, and I.C.I. Central Toxicology Laboratory, Alderley Park, Alderley Edge, Cheshire, England.
Über die Extraktion von Bakterien mit Phenol/Wasser (1952)

Es werden zwei einfache Verfahren zur Extraktion von Bakterien mit Phenol/Wasser angegeben. Nach Behandlung von gramnegativen Bakterien mit Phenol/Wasser-Emulsionen in der Kälte während weniger Minuten erhält man in der wäßrigen Phase die somatischen Glykoproteide der Bakterien (hauptsächlich 0-Antigene) in praktisch quantitativer Ausbeute. Nach Extraktion der Bakterien mit erwärmten, homogenen Phenol/Wasser-Mischungen und Trennen der Phasen in der Kälte finden sich in der wäßrigen Phase die proteinfreien Polysaccharide neben Nucleinsäuren. Einige chemische und immunologische Eigenschaften der nach den beiden Verfahren dargestellten Glykoproteide und Polysaccharide werden beschrieben.
The impact of Th17 cells on transplant rejection and the induction of tolerance (2010)

The capacity of Th17 cells to cause allograft rejection is becoming increasingly clear. However, the role and contribution of Th17 cells in allograft rejection in the presence of the full orchestra of T helper cells remains elusive. The apparent resistance of Th17 to be suppressed by Tregs may pose a hurdle for effective immunosuppression and tolerance inducing protocols. Furthermore, the close developmental pathways of Th17 and Tregs and the ability of Tregs to convert into Th17 cells in the presence of inflammatory signals may impede the establishment of specific unresponsiveness to donor alloantigens in vivo.
True (2000)

To assess the role of interleukin-4 (IL-4) and interleukin-13 (IL-13) in colon cancer cell-cell adhesion, we investigated the effect of both cytokines in human colon cancer cell line, colo205 cell-cell adhesion. IL-4 receptor was expressed on the cell surface of colo205, and recombinant IL-4 inhibited colo205 cell-cell adhesion in a dose-dependent fashion without inhibiting cell proliferation. Flow cytometric analysis revealed that monoclonal antibodies (mAbs) directed against E-cadherin and carcinoembryonic antigen (CEA) inhibited colo205 cell-cell adhesion and IL-4 significantly inhibited the expression of E-cadherin and CEA. IL-13 also inhibited colo205 cell-cell adhesion. These results indicated that IL-4 and IL-13 inhibited colon cancer cell-cell adhesion by down-regulation of E-cadherin and CEA molecules. We then investigated the expression of both cytokines from freshly isolated colon cancer tumour-infiltrating lymphocytes (TILs). With reverse transcription-polymerase chain reaction and flow cytometric analysis, we demonstrated that colon TILs expressed IL-4 and IL-13 mRNA and protein. These results suggest that Th 2 type cytokines IL-4 and IL-13 locally-produced from TILs may regulate colon cancer adhesion by down-regulation of adhesion molecules.
Tumor-specific cytolysis by lymphocytes infiltrating human melanomas. (1989)

Tumor infiltrating lymphocytes (TIL) were grown in IL-2 from single cell tumor suspensions of 14 human melanomas resected from 12 patients. As a function of time in culture, 4 of 14 TIL cultures eventually expressed highly specific cytolytic activity against fresh autologous melanoma targets in short term chromium release assays, failing to lyse multiple allogeneic tumors or autologous normal cells. These highly specific TIL were identified as CTL by phenotype (CD3+/CD4-/CD8+/Leu7-) and by function (lysis inhibited by antibodies directed against CD3 and MHC class I molecules). Cell separation experiments using immunomagnetic beads identified a highly tumor-specific CTL subpopulation within a nonspecific TIL culture, suggesting that the lytic activity of tumor-specific CTL may be diluted by the nonspecific killer activity present in heterogeneous TIL cultures. These studies provide evidence for specific MHC-restricted human immune responses against autologous tumor in cancer-bearing patients, and may be of importance to ongoing clinical trials using TIL in the immunotherapy of advanced malignancies.
Murine beta 1,4-galactosyltransferase: both the amounts and structure of the mRNA are regulated during spermatogenesis. (1990)

Previously we have shown that the gene encoding murine beta 1,4-galactosyltransferase (beta 1,4-GT; UDPgalactose:N-acetyl-D-glucosaminyl-glycopeptide 4-beta-D-galactosyltransferase, EC 2.4.1.38) is unusual in that it specifies two sets of mRNAs of about 3.9 and 4.1 kilobases (kb). Translation of the 3.9- and 4.1-kb mRNAs results in the predicted synthesis of two related membrane-bound forms of the protein of 386 amino acids (short form) and 399 amino acids (long form), respectively. In this study we have examined the expression of beta 1,4-GT during murine spermatogenesis. Spermatogonia contain a 4.1-kb transcript that is comparable in size to the beta 1,4-GT mRNA identified in somatic cells. During differentiation from spermatogonia (2n) to pachytene spermatocytes (4n), the amount of beta 1,4-GT mRNA is reduced to barely detectable levels. Continued differentiation to round spermatids (n) is coincident with a renewed production of beta 1,4-GT mRNA to levels comparable with those detected in spermatogonia. However, the characteristic 4.1-kb mRNA detected in spermatogonia is replaced by two truncated transcripts of 2.9 and 3.1 kb. By S1 nuclease analysis, the 2.9- and 3.1-kb transcripts were shown to encode the same open reading frame as the 4.1-kb transcript found in somatic cells. The shorter round spermatid transcripts arise as a consequence of the use of alternative poly(A) signals. Lastly, we show that, in direct contrast to all somatic tissues and cell lines examined to date, male germ cells synthesize only the long form of the beta 1,4-GT polypeptide.