gebhart/patrepeval huggingface dataset:
Adenovirus E1A, simian virus 40 tumor antigen, and human papillomavirus E7 protein share the capacity to disrupt the interaction between transcription factor E2F and the retinoblastoma gene product. (1992)

The adenovirus E1A gene product, the simian virus 40 large tumor antigen, and the human papillomavirus E7 protein share a short amino acid sequence that constitutes a domain required for the transforming activity of these proteins. These sequences are also required for these proteins to bind to the retinoblastoma gene product (pRb). Recent experiments have shown that E1A can dissociate complexes containing the transcription factor E2F bound to pRb, dependent on this conserved sequence element. We now show that the E7 protein and the simian virus 40 large tumor antigen can dissociate the E2F-pRb complex, dependent on this conserved sequence element. We also find that the E2F-pRb complex is absent in various human cervical carcinoma cell lines that either express the E7 protein or harbor an RB1 mutation, suggesting that the loss of the E2F-pRb interaction may be an important aspect in human cervical carcinogenesis. We suggest that the ability of E1A, the simian virus 40 large tumor antigen, and E7 to dissociate the E2F-pRb complex may be a common activity of these viral proteins that has evolved to stimulate quiescent cells into a proliferating state so that viral replication can proceed efficiently. In circumstances in which a lytic infection does not proceed, the consequence of this action may be to initiate the oncogenic process in a manner analogous to the mutation of the RB1 gene.
Pilot-Scale Production of Fatty Acid Ethyl Esters by an Engineered Escherichia coli Strain Harboring the p(Microdiesel) Plasmid (2010)

Fatty acid ethyl esters (FAEEs) were produced in this study by the use of an engineered Escherichia coli p(Microdiesel) strain. Four fed-batch pilot scale cultivations were carried out by first using glycerol as sole carbon source for biomass production before glucose and oleic acid were added as carbon sources. Cultivations yielded a cell density of up to 61 +/- 3.1 g of cell dry mass (CDM) per liter and a maximal FAEE content of 25.4% +/- 1.1% (wt/wt) of CDM.
Prolonged survival in rat liver transplantation with mouse monoclonal antibody against an inducible costimulator (ICOS)1 (2002)

T-cell activation through the ICOS costimulatory pathway plays an important role in graft rejection, and manipulating its pathway is an effective method for modulating transplantation immunity.
Syndiotactic Poly(1‐oxo‐2‐phenyltrimethylene): On the Mode of the Chain Growth under Palladium Catalysis (1991)

Selection between the enantiotopic faces of an olefin occurs in the sterically controlled carbonylation of styrene with [Pd(phen)(p-CH3C6H4SO3)2] as catalyst to give the title compound 1. The identification of the polymer end groups and the parallel reactions with other catalytic systems shed light on the mechanism of the reaction.
Eight-Year Results of a Randomized Clinical Trial Comparing Total Mastectomy and Lumpectomy with or without Irradiation in the Treatment of Breast Cancer (1989)

In 1985 we presented results of a randomized trial involving 1843 women followed for five years that indicated that segmental breast resection (lumpectomy) followed by breast irradiation is appropriate therapy for patients with Stage I or II breast cancer (tumor size, less than or equal to 4 cm), provided that the margins of the resected specimens are free of tumor. Women with positive axillary nodes received adjuvant chemotherapy. Lumpectomy followed by irradiation resulted in a five-year survival rate of 85 percent, as compared with 76 percent for total mastectomy, a rate of survival free of distant disease of 76 percent, as compared with 72 percent, and a disease-free survival rate of 72 percent, as compared with 66 percent. In the current study, we have extended our observations through eight years of follow-up. Ninety percent of the women treated with breast irradiation after lumpectomy remained free of ipsilateral breast tumor, as compared with 61 percent of those not treated with irradiation after lumpectomy (P less than 0.001). Among patients with positive axillary nodes, only 6 percent of those treated with radiation and adjuvant chemotherapy had a recurrence of tumor in the ipsilateral breast. Lumpectomy with or without irradiation of the breast resulted in rates of disease-free survival (58 +/- 2.6 percent), distant-disease-free survival (65 +/- 2.6 percent), and overall survival (71 +/- 2.6 percent) that were not significantly different from those observed after total mastectomy (54 +/- 2.4 percent, 62 +/- 2.3 percent, and 71 +/- 2.4 percent, respectively). There was no significant difference in the rates of distant-disease-free survival (P = 0.2) or survival (P = 0.3) among the women who underwent lumpectomy (with or without irradiation), despite the greater incidence of recurrence of tumor in the ipsilateral breast in those who received no radiation. We conclude that our observations through eight years are consistent with the findings at five years and that these new findings continue to support the use of lumpectomy in patients with Stage I or II breast cancer. We also conclude that irradiation reduces the probability of local recurrence of tumor in patients treated with lumpectomy.
Phosphorothioate Oligodeoxynucleotides: What Is Their Origin and What Is Unique About Them? (2000)

The development of nucleoside phosphorothioates is described in its historical context. Examples of the interaction of phosphorothioate groups, present either in oligodeoxynucleotides or in DNA, with nucleases are presented. The structural features responsible for the resistance of the phosphorothioates toward degradation by nucleases are discussed, as are the possible reasons for the high-affinity interaction of phosphorothioate oligodeoxynucleotides with certain proteins.
Pathogen-Specific CD8 T Cell Responses Are Directly Inhibited by IL-10 (2007)

Regulation of CD8 T cell expansion and contraction is essential for successful immune defense against intracellular pathogens. IL-10 is a regulatory cytokine that can restrict T cell responses by inhibiting APC functions. IL-10, however, can also have direct effects on T cells. Although blockade or genetic deletion of IL-10 enhances T cell-mediated resistance to infections, the extent to which IL-10 limits in vivo APC function or T cell activation/proliferation remains unknown. Herein, we demonstrate that primary and memory CD8 T cell responses following Listeria monocytogenes infection are enhanced by the absence of IL-10. Surface expression of the IL-10R is transiently up-regulated on CD8 T cells following activation, suggesting that activated T cells can respond to IL-10 directly. Consistent with this notion, CD8 T cells lacking IL-10R2 underwent greater expansion than wild-type T cells upon L. monocytogenes infection. The absence of IL-10R2 on APCs, in contrast, did not enhance T cell responses following infection. Our studies demonstrate that IL-10 produced during bacterial infection directly limits expansion of pathogen-specific CD8 T cells and reveal an extrinsic regulatory mechanism that modulates the magnitude of memory T cell responses.
Targeted Mutagenesis of Duplicated Genes in Soybean with Zinc-Finger Nucleases (2011)

We performed targeted mutagenesis of a transgene and nine endogenous soybean (Glycine max) genes using zinc-finger nucleases (ZFNs). A suite of ZFNs were engineered by the recently described context-dependent assembly platform--a rapid, open-source method for generating zinc-finger arrays. Specific ZFNs targeting dicer-like (DCL) genes and other genes involved in RNA silencing were cloned into a vector under an estrogen-inducible promoter. A hairy-root transformation system was employed to investigate the efficiency of ZFN mutagenesis at each target locus. Transgenic roots exhibited somatic mutations localized at the ZFN target sites for seven out of nine targeted genes. We next introduced a ZFN into soybean via whole-plant transformation and generated independent mutations in the paralogous genes DCL4a and DCL4b. The dcl4b mutation showed efficient heritable transmission of the ZFN-induced mutation in the subsequent generation. These findings indicate that ZFN-based mutagenesis provides an efficient method for making mutations in duplicate genes that are otherwise difficult to study due to redundancy. We also developed a publicly accessible Web-based tool to identify sites suitable for engineering context-dependent assembly ZFNs in the soybean genome.
Sphingosine 1-Phosphate Induces Platelet Activation through an Extracellular Action and Shares a Platelet Surface Receptor with Lysophosphatidic Acid (1997)

Sphingosine 1-phosphate (Sph-1-P) has been implicated as an intracellular second messenger in many studies. We investigated the metabolism of Sph-1-P and the mechanism by which Sph-1-P induces activation in enucleated and highly differentiated platelets. Platelets lack Sph-1-P lyase activity, possess persistently active sphingosine (Sph) kinase, and abundantly store Sph-1-P. Although exogenous Sph-1-P activated platelets, intracellular Sph-1-P, formed from exogenously added Sph by cytosolic Sph kinase, failed to do so. To support the notion that exogenous Sph-1-P stimulates platelets from outside, contact of platelet surfaces with immobilized Sph-1-P covalently linked to glass particles resulted in platelet activation. Furthermore, we detected the specific binding sites for radiolabeled Sph-1-P on the platelet surface, suggesting extracellular effects of Sph-1-P on plasma membrane receptors. This specific Sph-1-P binding was inhibited not by other sphingolipids but by lysophosphatidic acid (LPA), and platelet aggregation response to LPA was specifically desensitized by prior addition of Sph-1-P. Finally, internally stored Sph-1-P is released extracellularly upon stimulation, and the release correlated well with protein kinase C activation in intact platelets. These results suggest that Sph-1-P acts not intracellularly but intercellularly, following discharge from activated platelets, and shares a platelet surface receptor with LPA.
Blockade of α5β1 Integrins Reverses the Inhibitory Effect of Tenascin on Chemotaxis of Human Monocytes and Polymorphonuclear Leukocytes Through Three-Dimensional Gels of Extracellular Matrix Proteins (2001)

Tenascin is an extracellular matrix protein found in adults in T cell-dependent areas of lymphoid tissues, sites of inflammation, and tumors. We report here that it inhibited chemotaxis of chemoattractant-stimulated human monocytes and chemoattractant-stimulated polymorphonuclear leukocytes (PMN) through three-dimensional gels composed of collagen I or Matrigel, and chemotaxis of leukotriene B4-stimulated PMN through fibrin gels. The inhibitory effect of tenascin on monocyte or PMN chemotaxis through these matrices was reversed by Abs directed against alpha5beta1 integrins or by a peptide (GRGDSP) that binds to beta1 integrins. Tenascin did not affect leukotriene B4- or fMLP-stimulated expression of beta1 or beta2 integrins, but did exert a small inhibitory effect on PMN adhesion and closeness of apposition to fibrin(ogen)-containing surfaces. Thus, alpha5beta1 integrins mediate the inhibitory effect of tenascin on monocyte and PMN chemotaxis, without promoting close apposition between these leukocytes and surfaces coated with tenascin alone or with tenascin bound to other matrix proteins. This contrasts with the role played by alpha5beta1 integrins in promoting close apposition between fMLP-stimulated PMN and fibrin containing surfaces, thereby inhibiting chemotaxis of fMLP-stimulated PMN through fibrin gels. Thus, chemoattractants and matrix proteins regulate chemotaxis of phagocytic leukocytes by at least two different mechanisms: one in which specific chemoattractants promote very tight adhesion of leukocytes to specific matrix proteins and another in which specific matrix proteins signal cessation of migration without markedly affecting strength of leukocyte adhesion.
Gene Expression Profiling by Microarrays: Clinical Implications (2006)

Microarray analysis is a highly efficient tool for assessing the expression of a large number of genes simultaneously, and offers a new means to classify cancer and other diseases. Gene expression profiling can also be used to predict clinical outcome and response to specific therapeutic agents. This survey spans recent applications of microarrays in clinical medicine, covering malignant disease including acute leukaemias, lymphoid malignancies and breast cancer, together with diabetes and heart disease. Investigators in oncology, pharmacology and related clinical sciences, as well as basic scientists, will value this review of a promising new diagnostic and prognostic technology
Effective Student Teacher Supervision in the Era of No Child Left Behind (2008)

This research study addresses the issues and challenges for university supervisors of providing supervisory feedback in the accountability climate of No Child Left Behind. Several findings are detailed in the case below and include the following: (a) Feedback on individual learning needs of students differed between informal written observations and the formal feedback provided on midterm and final evaluations; (b) the supervisor’s perception of a teacher candidate’s success influenced the degree to which the feedback aligned with performance standards; (c) within the context of culturally and linguistically diverse classrooms, supervisory feedback included attention to individual learning needs when teacher candidates were viewed as successful by the supervisor; and (d) for those candidates who struggled in their teaching, adherence to specific standards took precedence over the individual needs of students in the classroom.
Hydrolytic reactions of cyclic bis(3′‐5′)diadenylic acid (c‐di‐AMP) (2012)

Hydrolytic reactions of cyclic bis(3′‐5′)diadenylic acid (c‐di‐AMP) have been followed by Reversed phase high performance liquid chromatography (RP‐HPLC) over a wide pH range at 90 °C. Under neutral and basic conditions (pH ≥ 7), disappearance of the starting material (first‐order in [OH − ]) was accompanied by formation of a mixture of adenosine 2′‐monophosphate and 3′‐monophosphate (2′‐AMP and 3′‐AMP). Under very acidic conditions (from H 0 = −0.7 to 0.2), c‐di‐AMP undergoes two parallel reactions (first‐order in [H + ]): the starting material is cleaved to 2′‐AMP and 3′‐AMP and depurinated to adenine (i.e., cleavage of the N ‐glycosidic bond), the former reaction being slightly faster than the latter one. At pH 1–3, isomerization to cyclic bis(2′‐5′)diadenylic acid competes with the depurination. Copyright © 2012 John Wiley &amp; Sons, Ltd.
LFA-1 Expression on Target Cells Promotes Human Immunodeficiency Virus Type 1 Infection and Transmission (2001)

ABSTRACT While CD4 and the chemokine receptors are the principal receptors for human immunodeficiency virus (HIV), other cellular proteins, such as LFA-1, are also involved in HIV infection. LFA-1 and its ligands, ICAM-1, ICAM-2, and ICAM-3, can be expressed on the cells infected by HIV, as well as on the HIV virions themselves. To examine the role of LFA-1 expressed on target cells in HIV infection, Jurkat-derived Jβ2.7 T-cell lines that express either wild-type LFA-1, a constitutively active mutant LFA-1, or no LFA-1 were used. The presence of wild-type LFA-1 enhanced the initial processes of HIV infection, as well as the subsequent replication and transmission from cell to cell. In contrast, the constitutively active LFA-1 mutant failed to promote virus replication and spread, even though this mutant could help HIV enter cells and establish the initial infection. This study clearly demonstrates the contribution of LFA-1 in the different stages of HIV infection. Moreover, not only is LFA-1 expression important for initial HIV-cell interaction, subsequent replication, and transmission, but its activity must also be properly regulated.
RNA sequencing reveals the role of splicing polymorphisms in regulating human gene expression (2010)

Expression levels of many human genes are under the genetic control of expression quantitative trait loci (eQTLs). Despite technological advances, the precise molecular mechanisms underlying most eQTLs remain elusive. Here, we use deep mRNA sequencing of two CEU individuals to investigate those mechanisms, with particular focus on the role of splicing control loci (sQTLs). We identify a large number of genes that are differentially spliced between the two samples and associate many of those differences with nearby single nucleotide polymorphisms (SNPs). Subsequently, we investigate the potential effect of splicing SNPs on eQTL control in general. We find a significant enrichment of alternative splicing (AS) events within a set of highly confident eQTL targets discovered in previous studies, suggesting a role of AS in regulating overall gene expression levels. Next, we demonstrate high correlation between the levels of mature (exonic) and unprocessed (intronic) RNA, implying that ∼75% of eQTL target variance can be explained by control at the level of transcription, but that the remaining 25% may be regulated co- or post-transcriptionally. We focus on eQTL targets with discordant mRNA and pre-mRNA expression patterns and use four examples: USMG5, MMAB, MRPL43, and OAS1, to dissect the exact downstream effects of the associated genetic variants.
Nitrogen Balance in and Export from an Agricultural Watershed (1997)

Abstract Surface water nitrate (NO − 3 ) pollution from agricultural production is well established, although few studies have linked field N budgets, NO − 3 loss in tile drained watersheds, and surface water NO − 3 loads. This study was conducted to determine field sources, transport, and river export of NO − 3 from an agricultural watershed. The Embarras River watershed at Camargo (48 173 ha) in east‐central Illinois was investigated. The watershed is a tile‐drained area of fertile Mollisols (typical soil is Drummer silty clay loam, a fine‐silty, mixed mesic Typic Haplaquoll) with primary cropping of maize ( Zea mays L.) and soybean ( Glycine max L.). Agricultural field N sources and sinks, tile drainage NO − 3 concentrations and fluxes, and river NO − 3 export were estimated for the entire watershed. Large pools of inorganic N were present following each harvest of maize and soybean (average of 3670 Mg N yr −1 over a 6‐yr period). The source of most of the inorganic N was divided between N fertilizer and soil mineralized N. High concentrations of NO − 3 were found in four monitored drainage tiles (5–49 mg N L −1 ), and tile concentrations of NO − 3 were synchronous with Embarras River NO − 3 concentrations. High flow events contributed most of the yearly NO − 3 loss (24.7 kg N ha −1 yr −1 ) from tile drained fields in the 1995 water year (1 Oct. 1994 through 30 Sept. 1995) where high rainfall events occurred in a low overall precipitation year (in one tile 21% of the annual load was exported in 1 d). During the 1996 water year, NO − 3 export in tiles was much higher (44.2 kg N ha −1 yr −1 ) due to greater precipitation, and individual days were less important. On average, about 49% (average of 1688 Mg N yr −1 over a 6‐yr period) of the field inorganic N pool was estimated to be leached through drain tiles and seepage and was exported by the Embarras River, although depending on weather and field N balances this ranged from 25 to 85% of the field N balance over the 6‐yr period. It seems likely that agricultural disturbance (high mineralization inputs of N) and N fertilization combined with tile drainage contributed significantly to NO − 3 export in the Embarras River.
Identification of clustered cells in human hair follicle responsible for MMP‐9 gelatinolytic activity: consequences for the regulation of hair growth (2001)

Cytokine- and EGF-induced upregulation of MMP-9 in the lower epithelial compartment of the human hair bulb is a major mechanism through which hair follicle involution, observed in alopecia, may occur.
A cross-layer design for scalable mobile video (2011)

Today's mobile video suffers from two limitations: 1) it cannot reduce bandwidth consumption by leveraging wireless broadcast to multicast popular content to interested receivers, and 2) it lacks robustness to wireless interference and errors. This paper presents SoftCast, a cross-layer design for mobile video that addresses both limitations. To do so, SoftCast changes the network stack to act like a linear transform. As a result, the transmitted video signal becomes linearly related to the pixels' luminance. Thus, when noise perturbs the transmitted signal samples, the perturbation naturally translates into approximation in the original video pixels. This enables a video source to multicast a single stream that each receiver decodes to a video quality commensurate with its channel quality. It also increases robustness to interference and errors which now reduce the sharpness of the received pixels but do not cause the video to glitch or stall. We have implemented SoftCast and evaluated it in a testbed of software radios. Our results show that it improves the average video quality for multicast users by 5.5dB, eliminates video glitches caused by mobility, and increases robustness to packet loss by an order of magnitude.
Adaptive Logarithmic Mapping For Displaying High Contrast Scenes (2003)

Abstract We propose a fast, high quality tone mapping technique to display high contrast images on devices with limited dynamicrange of luminance values. The method is based on logarithmic compression of luminance values, imitatingthe human response to light. A bias power function is introduced to adaptively vary logarithmic bases, resultingin good preservation of details and contrast. To improve contrast in dark areas, changes to the gamma correctionprocedure are proposed. Our adaptive logarithmic mapping technique is capable of producing perceptually tunedimages with high dynamic content and works at interactive speed. We demonstrate a successful application of ourtone mapping technique with a high dynamic range video player enabling to adjust optimal viewing conditions forany kind of display while taking into account user preference concerning brightness, contrast compression, anddetail reproduction. Categories and Subject Descriptors (according to ACM CCS): I.3.3 [Image Processing and Computer Vision]: Image Representation