gebhart/patrepeval huggingface dataset:
Salmonella mutagenicity tests: IV. Results from the testing of 300 chemicals (1988)

Three hundred chemicals were tested for mutagenicity, under code, in Salmonella typhimurium, using a preincubation protocol. All tests were performed in the absence of exogenous metabolic activation, and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters. The results and data from these tests are presented.
Vitreous Changes in Retinal Branch Vein Occlusion (1987)

<h3>To the Editor.</h3> —Dr Brooks and colleagues<sup>1</sup>raised the question as to whether the vitreoretinal relationship can be used as an indicator of the risk for progression in an eye with retinal branch vein occlusion (RBVO). We reported the vitreous findings in a group of 50 eyes with RBVO and compared these findings with those of an age-matched control group.<sup>2</sup>As Brooks and coworkers suggest, our findings were similar to those reported later in our diabetic patients.<b>3</b> The incidence of partial vitreous detachment was significantly higher (22%) in the RBVO group than in the control group (2.2% ) (<i>P</i>&lt;.01). The incidence of preretinal neovascularization was 22%. No new vessels formed in eyes with complete posterior vitreous detachment. Sixty-four percent of the eyes with preretinal neovascularization had partial posterior vitreous detachment, while 36% had no vitreous detachment. In the eyes without preretinal neovascularization, 90% had either no vitreous detachment
Structure of the Endoglucanase I from Fusarium oxysporum:  Native, Cellobiose, and 3,4-Epoxybutyl β-d-Cellobioside-Inhibited Forms, at 2.3 Å Resolution, (1997)

The mechanisms involved in the enzymatic degradation of cellulose are of great ecological and commercial importance. The breakdown of cellulose by fungal species is performed by a consortium of free enzymes, known as cellobiohydrolases and endoglucanases, which are found in many of the 57 glycosyl hydrolase families. The structure of the endoglucanase I (EG I), found in glycosyl hydrolase family 7, from the thermophilic fungus Fusarium oxysporum has been solved at 2.3 A resolution. In addition to the native enzyme, structures have also been determined with both the affinity label, 3,4-epoxybutyl beta-D-cellobioside, and the reaction product cellobiose. The affinity label is covalently bound, as expected, to the catalytic nucleophile, Glu197, with clear evidence for binding of both the R and S stereoisomers. Cellobiose is found bound to the -2 and -1 subsites of the enzyme. In marked contrast to the structure of EG I with a nonhydrolyzable thiosaccharide analog, which spanned the -2, -1, and +1 subsites and which had a skew-boat conformation for the -1 subsite sugar [Sulzenbacher, G., et al. (1996) Biochemistry 35, 15280-15287], the cellobiose complex shows no pyranoside ring distortion in the -1 subsite, implying that strain is induced primarily by the additional +1 subsite interactions and that the product is found, as expected, in its unstrained conformation.
Design, Synthesis, and Photodynamics of Light-Harvesting Arrays Comprised of a Porphyrin and One, Two, or Eight Boron-Dipyrrin Accessory Pigments (1998)

Light-harvesting arrays containing one, two, or eight boron-dipyrrin (BDPY) pigments and one porphyrin (free base or Zn chelate) have been synthesized using a modular building block approach. The reaction of pyrrole and 4-(BDPY)benzaldehyde or 3,5-bis(BDPY)benzaldehyde, prepared by Pd-mediated ethynylation with the corresponding iodo-benzaldehydes, affords the desired BDPY-porphyrin array in yields of 10−58%. The arrays are soluble in organic solvents and have been characterized by static and time-resolved absorption and fluorescence spectroscopy. The blue-green BDPY absorption complements spectral coverage of the porphyrin chromophores and rivals the intensity of the porphyrin Soret band when eight BDPY accessory pigments are present. Efficient energy transfer from the BDPY pigment(s) to the porphyrin (free base or Zn-chelate) is observed in arrays containing one or two (>90%) or eight (>85%) accessory pigments per porphyrin. Biphasic excited-state decay behavior is exhibited by the BDPY pigments in isolated form and in the arrays. The time constants are ∼15 and ∼500 ps in the reference compounds (both reflecting deactivation to the ground state) and ∼2 and ∼20 ps in the arrays (both primarily reflecting energy transfer to the porphyrin). The longer-lived kinetic component comprises ∼70% of the decay in each case. Ab initio calculations suggest that the two kinetic components are associated with two energetically accessible excited-state conformers involving the boron-dipyrrin unit and the 5-aryl ring (which is integral to the linker in the arrays). The calculations and experimental results indicate that the two excited-state conformers differ from one another in structure (the planarity of the boron-dipyrrin unit and its orientation with respect to the 5-aryl ring), electronic composition (especially the electron density on the 5-aryl group of the boron-dipyrrin unit), radiative and nonradiative coupling to the ground state, and the rate of energy transfer to the porphyrin constituent in the arrays. The high energy-transfer efficiencies together with favorable light-absorption and chemical properties exhibited by the boron-dipyrrin pigments make them amenable for use in porphyrin-based arrays for molecular photonics applications.
Addressing sleep disturbances: An opportunity to prevent cardiometabolic disease? (2014)

There is increasing awareness of the role of sleep disturbance as an important factor in health and disease. Although sub-clinical sleep disturbances (insufficient sleep duration or inadequate sleep quality) may be difficult to assess with conceptual and/or methodological clarity, this review attempts to summarize and synthesize these findings. First, the concept of sleep disturbance in a public health context is introduced, to provide context and rationale. Second, operational definitions of 'cardiometabolic disease' and 'sleep disturbance' are offered, to address many unclear operationalizations. Third, the extant literature is summarized regarding short or long sleep duration and/or insufficient sleep, insomnia and insomnia symptoms, general (non-specific sleep disturbances), circadian rhythm abnormalities that result in sleep disturbances, and, briefly, sleep-disordered breathing. Fourth, the review highlights the social/behavioural context of sleep, including discussions of sleep and race/ethnicity, socio-economic position, and other social/environmental factors, in order to place these findings in a social-environmental context relevant to public health. Fifth, the review highlights the issue of sleep as a domain of health behaviour and addresses issues regarding development of healthy sleep interventions. Finally, a research agenda of future directions is proposed.
Potato virus X amplicon-mediated silencing of nuclear genes (1999)

Transgenic expression of a replicating potato virus X (PVX) construct (termed an 'amplicon') reproducibly and consistently activates post-transcriptional gene silencing (PTGS) in every plant. The amplicon-mediated PTGS mechanism can target transiently expressed RNAs that share homology with the amplicon transgene. We show that amplicons can also be used to silence stably integrated transgenes and endogenous genes. Plants expressing both a transgene and an amplicon targeting part of the transgene show low accumulation of the transgene RNA. Similarly, plants expressing an amplicon targeting an endogenous gene show low accumulation of the endogenous RNA and display a mutant phenotype matching a previously characterised mutation. These data demonstrate that PVX amplicons present a novel approach for the consistent activation of PTGS that can be used to specifically target and suppress gene expression in plants.
Involvement of Members of the Cadherin Superfamily in Cancer (2009)

We review the role of cadherins and cadherin-related proteins in human cancer. Cellular and animal models for human cancer are also dealt with whenever appropriate. E-cadherin is the prototype of the large cadherin superfamily and is renowned for its potent malignancy suppressing activity. Different mechanisms for inactivating E-cadherin/CDH1 have been identified in human cancers: inherited and somatic mutations, aberrant protein processing, increased promoter methylation, and induction of transcriptional repressors such as Snail and ZEB family members. The latter induce epithelial mesenchymal transition, which is also associated with induction of "mesenchymal" cadherins, a hallmark of tumor progression. VE-cadherin/CDH5 plays a role in tumor-associated angiogenesis. The atypical T-cadherin/CDH13 is often silenced in cancer cells but up-regulated in tumor vasculature. The review also covers the status of protocadherins and several other cadherin-related molecules in human cancer. Perspectives for emerging cadherin-related anticancer therapies are given.
The Periodontal Problems and Management of the Renal Transplant Patient (1994)

This review considers the periodontal problems of renal transplant patients with particular reference to their drug therapy and the pretransplant uremia. It would appear that either disease- or drug-induced immunosuppression affords the renal transplant patient a degree of "protection" against periodontal breakdown. However, of more significance to the periodontologist is the problem of drug-induced gingival overgrowth with reference to both cyclosporin and nifedipine. Approximately 30% of dentate renal transplant patients medicated with cyclosporin alone experience significant gingival overgrowth which requires surgical excision. This figure increases to 40% when patients are medicated with both drugs. The pathogenesis of this unwanted effect is uncertain and the relationship between the expression of gingival overgrowth and various periodontal or pharmacokinetic variables remains a contentious issue. Clinical measures to prevent the occurrence of either cyclosporin- or nifedipine-induced gingival overgrowth are unsatisfactory.
Differential binding of soybean agglutinin to human neuroblastoma cell lines: potential application to autologous bone marrow transplantation. (1985)

Normal human bone marrow cells were mixed with neuroblastoma cells from four different human cell lines, and the cell mixtures were separated by differential agglutination with soybean agglutinin (SBA). The unagglutinated cell fraction, previously shown to be highly enriched for the hematopoietic pluripotential stem cells and capable of reconstituting lethally irradiated adult patients with acute leukemia, was further fractionated by affinity chromatography on the lectin conjugated to Sepharose 6MB beads. Two independent assays, one using radiolabeling of the tumor cells and the other based on cloning of the neuroblastoma cells on agar, showed that the agglutination step alone removes 64-76% of the radiolabeled neuroblastoma cells and 85-98% of the clonogenic cells from the tumor/bone marrow cell mixture. Passage of the unagglutinated radiolabeled cells through SBA-Sepharose columns results in further purging of 28-53% of the neuroblastoma cells. Thus a combination of the two methods affords only one-log depletion for the neuroblastoma cells, compared to a three-log depletion achieved for a T-cell leukemia line CEM tested in parallel. It seems therefore that the agglutination technique, or the use of SBA-Sepharose columns, can be used only as a preliminary step for the purging of neuroblastoma cells from involved human bone marrow preparations. Staining with fluorescein isothiocyanate-conjugated SBA of nine different neuroblastoma cell lines, including the four tested in the fractionation studies, showed that more than 98% of the cells, of all the cell lines tested, specifically bind to the lectin, whereas no specific binding can be detected on the stem cell-enriched bone marrow cell fraction. However, the total number of receptors on the neuroblastoma cells is small compared to that of line CEM or normal granulocytes, which are strongly agglutinated by SBA. It seems therefore that the quantitative difference in the total number of SBA receptors is a crucial factor for purging by the agglutination technique or by affinity chromatography. Although these results show limitations to the use of both methods, this study establishes that all neuroblastoma cell lines tested express receptors for the lectin. Improved purging of neuroblastoma cells may possibly be achieved by targeting SBA-bound toxins or magnetic spheres to these receptors.
Expression and hormone regulation of prolactin receptors in rat dorsal and lateral prostate (1996)

We have studied the receptors that presumably mediate the biological effects of PRL in rat dorsal (DP) and lateral (LP) prostate. The PRL receptor proteins were localized to the glandular secretory epithelium of prostatic tissue by immunohistochemistry. Both the short and the long PRL receptor proteins were detected in DP and LP by Western blot analysis and cross-linking of [125I]human PRL to membrane preparations of DP and LP. Three messenger RNAs (mRNAs) for the long [1.3-1.7, 2.5, and 9.5-10 kilobases (kb)] and short (0.6-0.7, 3.0-4.6, and 10-12 kb) PRL receptors were expressed in dorsal and lateral lobes of rat prostate. Testosterone (T), estrogen (E), and PRL regulation of PRL receptor expression in rat DP and LP was studied in organ culture, which has been shown to be a suitable model to study hormone responses of prostatic tissue in vitro. The mRNAs of the short and long PRL receptors were differentially regulated in rat dorsolateral prostate. T, E, and PRL regulated the level of the long PRL receptor mRNAs in a tissue-specific manner, whereas hormone regulation of the short PRL receptor mRNAs was only modest. Furthermore, the hormonal responses of the different mRNA splicing variants of the long PRL receptor were not all similar; T, E, and PRL each increased the expression of 1.3- to 1.7-kb and 9.5- to 10-kb transcripts in DP, but only T did so in LP, whereas no clear regulation for the 2.5-kb mRNA could be observed in either tissue. This suggests that the hormonal regulation occurs at least at the posttranscriptional level. The effects of T and E were counteracted by the antihormones cyproterone and toremifene, respectively, indicating a specific receptor-mediated manner of steroid action.
Identification of a Putative Target for Rho as the Serine-Threonine Kinase Protein Kinase N (1996)

Rho, a Ras-like small guanosine triphosphatase, has been implicated in cytoskeletal responses to extracellular signals such as lysophosphatidic acid (LPA) to form stress fibers and focal contacts. The form of RhoA bound to guanosine triphosphate directly bound to and activated a serine-threonine kinase, protein kinase N (PKN). Activated RhoA formed a complex with PKN and activated it in COS-7 cells. PKN was phosphorylated in Swiss 3T3 cells stimulated with LPA, and this phosphorylation was blocked by treatment of cells with botulinum C3 exoenzyme. Activation of Rho may be linked directly to a serine-threonine kinase pathway.
Specific spatial and temporal distribution of retinoic acid receptor gamma transcripts during mouse embryogenesis (1990)

Retinoic acid (RA), a putative morphogen in vertebrates, has profound effects on development during embryogenesis, chondrogenesis and differentiation of squamous epithelia. The distribution of the transcripts of the retinoic acid receptor gamma (RAR-gamma) gene has been studied here by in situ hybridization during mouse development from days 6.5 to 15.5 post-coïtum (p.c.). RAR-gamma transcripts are detected as early as day 8 p.c. in the presomitic posterior region. Between days 9.5 and 11.5 p.c., the transcripts are uniformly distributed in the mesenchyme of the frontonasal region, pharyngeal arches, limb buds and sclerotomes. At day 12.5 p.c., RAR-gamma transcripts are found in all precartilaginous mesenchymal condensations. From day 13.5 p.c., the transcripts are specifically localized in all cartilages and differentiating squamous keratinizing epithelia, irrespective of their embryological origin. RAR-gamma transcripts are also found in the developing teeth and whisker follicles. The developmental pattern of expression of the RAR-gamma gene suggests that RAR-gamma plays a crucial role for transducing RA signals at the level of gene expression during morphogenesis, chondrogenesis and differentiation of squamous epithelia.
Lao PDR - Trade and transport facilitation assessment (2014)

In Lao People's Democratic Republic (PDR), the value of trade has risen rapidly over the last decade with both imports and exports increasing by average annual rate of 24 percent. This report examines the trade logistics of Lao PDR. A trade and transport facilitation assessment was performed using a standardized toolkit and methodology developed by the World Bank to evaluate the quality of the logistics services. The assessment focused on the services used by these trades and the corridors used by these services. The assessment gave specific attention to two constraints on trade, the location of the country and the size of the trade. The study is organized in three interrelated parts: assessing the performance of the logistics sector; the international trade corridors linking Lao PDR to trade gateways in Thailand; and the supply chains used for distribution of exports. This report is presented in four sections. The first part examines the foreign trade of Lao PDR, the opportunities for growth and the logistics services in the movement of imports and exports between the country and its major gateways. The second section evaluates the performance of the corridors connecting the major origins and destinations in the country and the principal seaport used for international trade. The third section analyses the structure and performance characteristics of the supply chains used for selected trades and the implications for restructuring to support growth in the export trade. The final section presents a series of recommendations for improving the competitiveness of the exports through improvements in the structure of the supply chains, the logistics services used by these supply chains, and the corridors used by these supply chains.
IL-21 Is Required to Control Chronic Viral Infection (2009)

CD4+ and CD8+ T cell functions are rapidly aborted during chronic infection, preventing viral clearance. CD4+ T cell help is required throughout chronic infection so as to sustain CD8+ T cell responses; however, the necessary factor(s) provided by CD4+ T cells are currently unknown. Using a mouse model of chronic viral infection, we demonstrated that interleukin-21 (IL-21) is an essential component of CD4+ T cell help. In the absence of IL-21 signaling, despite elevated CD4+ T cell responses, CD8+ T cell responses are severely impaired. CD8+ T cells directly require IL-21 to avoid deletion, maintain immunity, and resolve persistent infection. Thus, IL-21 specifically sustains CD8+ T cell effector activity and provides a mechanism of CD4+ T cell help during chronic viral infection.
An Overview of Underbalanced Drilling Applications in Canada (1995)

Abstract Underbalanced drilling is quickly becoming an important technology in the Canadian oil and gas sector. While drilling impairment has always been a concern, a significant increase in horizontal completions has brought this issue to the forefront. A number of stimulation techniques are available for overcoming impairment in vertical wells or shallow damage in horizontal wells, however, deeper matrix damage is often difficult to remove in long horizontal sections. With this in mind, Canadian producers have looked to underbalanced drilling to prevent damage caused by fluid leak-off and fines migration. Many of the oil and gas fields in Canada are subhydrostatic, therefore underbalanced drilling operations often require the entrainment of a gas phase in the drilling fluid to generate the appropriate bottomhole pressures. In most cases, because of safety concerns, nitrogen gas is used. Two basic styles of nitrified underbalanced drilling are currently used with conventional rig drilling operations. One involves injecting nitrogen at the standpipe to co-mingle with the drilling fluid. The other, referred to as parasite injection, utilizes an external gas injection conduit that allows gasification of the drilling fluid in the vertical annulus. Either approach has specific advantages which must be considered for each application. An essential component of underbalanced drilling (UBD) success is effective two-phase flow modeling. Initial simulation is required to investigate and optimize various design options in the planning stage. This is often followed up by providing onsite support to assess actual job parameters and make any required design modifications. This paper focuses on these two UBD techniques, addressing the advantages and limitations of each. Two-phase flow analysis and job design will be discussed. A summary of the jobs completed, operational details and production results will be given.
Phase-resolved magnetomotive OCT for imaging nanomolar concentrations of magnetic nanoparticles in tissues (2008)

Magnetic nanoparticles (MNPs) are increasingly important in magnetic resonance and biomedical optical imaging. We describe a method for imaging MNPs by detecting nanoscale displacements using a phase-resolved spectral-domain optical coherence tomography (OCT) system. Biological tissues and phantoms are exposed to approximately 800 G magnetic fields modulated at 56 and 100 Hz to mechanically actuate embedded iron oxide MNPs (approximately 20 nm diameter). Sensitivity to 27 microg/g (approximately 2 nM) MNPs within tissue phantoms is achieved by filtering paramagnetic from diamagnetic vibrations. We demonstrate biological feasibility by imaging topically applied MNPs during their diffusion into an excised rat tumor over a 2 hour time period.
Modification of Surface Membrane Antigens by Trypsin (1975)

Cultured 3T3 and PY-3T3 mouse fibroblasts were subjected to mild treatment with twice crystallized trypsin and their immunogenicity tested in ICR/CD-1 mice. Surface antigenic modifications were observed using the foot pad swelling assay for detection of delayed hypersensitive responses. Mice immunized with trypsin-treated 3T3 cells showed cell-mediated immune reactions following challenge with either homologous antigen or untreated PY-3T3 fibroblasts. In contrast, treatment of the virus-transformed cells with trypsin decreased their antigenicity as determined by this in vivo assay.
Hypoxia-Inducible Regulation of a Prodrug-Activating Enzyme for Tumor-Specific Gene Therapy (2002)

Previous studies have suggested that tumor hypoxia could be exploited for cancer gene therapy. Using hypoxia-responsive elements derived from the human vascular endothelial growth factor gene, we have generated vectors expressing a bacterial nitroreductase (NTR) gene that can activate the anticancer prodrug CB1954. Stable transfectants of human HT1080 tumor cells with hypoxia-inducible vectors were established with G418 selection. Hypoxic induction of NTR protein correlated with increased sensitivity to in vitro exposure of HT1080 cells to the prodrug. Growth delay assays were performed with established tumor xenografts derived from the same cells to detect the in vivo efficacy of CB1954 conversion to its cytotoxic form. Significant antitumor effects were achieved with intraperitoneal injections of CB1954 both in tumors that express NTR constitutively or with a hypoxia-inducible promoter. In addition, respiration of 10% 02 increased tumor hypoxia in vivo and enhanced the antitumor effects. Taken together, these results demonstrate that hypoxia-inducible vectors may be useful for tumor-selective gene therapy, although the problem of delivery of the vector to the tumors, particularly to the hypoxic cells in the tumors, is not addressed by these studies.