gebhart/patrepeval huggingface dataset:
Integrated protein quality-control pathways regulate free α-globin in murine β-thalassemia (2012)

Cells remove unstable polypeptides through protein quality-control (PQC) pathways such as ubiquitin-mediated proteolysis and autophagy. In the present study, we investigated how these pathways are used in β-thalassemia, a common hemoglobinopathy in which β-globin gene mutations cause the accumulation and precipitation of cytotoxic α-globin subunits. In β-thalassemic erythrocyte precursors, free α-globin was polyubiquitinated and degraded by the proteasome. These cells exhibited enhanced proteasome activity, and transcriptional profiling revealed coordinated induction of most proteasome subunits that was mediated by the stress-response transcription factor Nrf1. In isolated thalassemic cells, short-term proteasome inhibition blocked the degradation of free α-globin. In contrast, prolonged in vivo treatment of β-thalassemic mice with the proteasome inhibitor bortezomib did not enhance the accumulation of free α-globin. Rather, systemic proteasome inhibition activated compensatory proteotoxic stress-response mechanisms, including autophagy, which cooperated with ubiquitin-mediated proteolysis to degrade free α-globin in erythroid cells. Our findings show that multiple interregulated PQC responses degrade excess α-globin. Therefore, β-thalassemia fits into the broader framework of protein-aggregation disorders that use PQC pathways as cell-protective mechanisms.
Identification of an Androgen-Dependent Enhancer within the Prostate Stem Cell Antigen Gene (2002)

Prostate stem cell antigen (PSCA) is emerging as an important diagnostic marker and therapeutic target in prostate cancer. Previous studies indicated that PSCA was directly regulated by androgens, but the mechanism has not been elucidated. Here we describe the identification of a compact cell-specific and androgen-responsive enhancer between 2.7 and 3 kb upstream of the transcription start site. The enhancer functions autonomously when positioned immediately adjacent to a minimal promoter. Deoxyribonuclease I footprinting analysis with recombinant androgen receptor (AR) reveals that the enhancer contains two AR binding sites at one end. Mutational analysis of the AR binding sites revealed the importance of the higher affinity one. The dissociation constant of the high affinity binding site (androgen response element I) was determined to be approximately 87 nM. The remainder of the enhancer contains elements that function synergistically with the AR. We discuss the structural organization of the PSCA enhancer and compare it with that found in other AR-regulated genes.
Li+-Ion Dynamics in β-Li3PS4 Observed by NMR: Local Hopping and Long-Range Transport (2018)

A detailed structural characterization is performed on β-Li3PS4 using 6Li and 31P magic-angle spinning NMR spectroscopy in combination with X-ray and neutron diffraction. High-temperature synchrotron X-ray diffraction was used to determine the phase stability and observe phase transitions. In addition, we investigated the Li+-ion dynamics by temperature-dependent 7Li NMR lineshape analysis, 7Li NMR relaxometry, and 7Li pulsed field-gradient (PFG) NMR measurements. A good agreement is obtained between the local hopping observed by T1 relaxation time measurements and the long-range transport investigated by PFG NMR with a Li+ diffusion coefficient of 9 × 10–14 m2/s at 298 K and an activation energy of 0.24 eV. From this, a Li+ conductivity of 1.0 × 10–4 S/cm is estimated, which corresponds well with impedance measurements on β-Li3PS4 pellets.
Pharmacologic Principles for Combination Therapy (2005)

This article discusses the pharmacologic basis for understanding the therapeutic actions of drugs, particularly for their use in combinations. The focus is on principles underlying combination therapy in general, including examples from diseases other than chronic obstructive pulmonary disease (COPD). Pharmacodynamic aspects of drug action are covered, with an emphasis on recent advances in the understanding of drug-receptor interactions and of drug agonism. Pharmacokinetics and drug-induced adaptive changes in receptors and cell signaling pathways are summarized, emphasizing their importance for potential combination therapies aimed at prolonging drug action. An organizational framework for three different approaches to combination therapy is then proposed; the molecular rationales for each approach are described together with classic examples from other diseases, and then their application to combination therapy in COPD is discussed. Finally, terminology for the independent and interactive effects of drug combinations is discussed, and approaches to the quantitative analysis and visual display of the effects of drug combinations are introduced. The basic principles reviewed here provide the pharmacologic foundation for subsequent articles in this issue that address the combinations in current use for COPD, and they point to novel strategies for potential future approaches to combination therapy in COPD.
Glycan gene expression signatures in normal and malignant breast tissue; possible role in diagnosis and progression (2009)

Glycosylation is the stepwise procedure of covalent attachment of oligosaccharide chains to proteins or lipids, and alterations in this process have been associated with malignant transformation. Simultaneous analysis of the expression of all glycan-related genes clearly gives the advantage of enabling a comprehensive view of the genetic background of the glycobiological changes in cancer cells. Studies focusing on the expression of the whole glycome have now become possible, which prompted us to review the present knowledge on glycosylation in relation to breast cancer diagnosis and progression, in the light of available expression data from tumors and breast tissue of healthy individuals. We used various data resources to select a set of 419 functionally relevant genes involved in synthesis, degradation and binding of N-linked and O-linked glycans, Lewis antigens, glycosaminoglycans (chondroitin, heparin and keratan sulfate in addition to hyaluronan) and glycosphingolipids. Such glycans are involved in a number of processes relevant to carcinogenesis, including regulation of growth factors/growth factor receptors, cell-cell adhesion and motility as well as immune system modulation. Expression analysis of these glycan-related genes revealed that mRNA levels for many of them differ significantly between normal and malignant breast tissue. An associative analysis of these genes in the context of current knowledge of their function in protein glycosylation and connection(s) to cancer indicated that synthesis, degradation and adhesion mediated by glycans may be altered drastically in mammary carcinomas. Although further analysis is needed to assess how changes in mRNA levels of glycan genes influence a cell's glycome and the precise role that such altered glycan structures play in the pathogenesis of the disease, lessons drawn from this study may help in determining directions for future research in the rapidly-developing field of glycobiology.
Tibiotarsal arthrodesis after astragalectomy; a report of eight cases. (1947)

In extirpation of the talus, in addition to the noticeable disfigurement of the ankle, some shortening of the extremity occurs with limitation of dorsiflexion. Disabling deformity occurs in some cases. Some ankles are definitely not stable, and consequently are painful. Deformities, especially if severe, demand operative correction, if all the criteria of a good foot and ankle are to be satisfied. This can be accomplished by tibiotarsal fusion.
Beds in the community (1988)

I feel that I must write to disagree with Charlotte Alderman who wrote in her article 'Pressure Drop' (Nursing Standard, week ending July 2) that wJ» beds and flotation beds are not suitable for use in the community. In this small rural area there has been a Clinitron bed in use for 18 months and a water bed in use for several years. The problem is not that the beds are unsuitable (although there can be complications if the home flooring is not strong enough) but that costs are high. The water bed can be purchased and the cost met either by the patient or by local charities; the Clinitron bed, however, cannot be purchased, but the rental may prove a cheaper option than long term hospitalisation. One has to justify the use of it clinically, however.
Transformation of 1- and 2-methylnaphthalene by Cunninghamella elegans (1984)

Cunninghamella elegans metabolized 1- and 2-methylnaphthalene primarily at the methyl group to form 1- and 2-hydroxymethylnaphthalene, respectively. Other compounds isolated and identified were 1- and 2-naphthoic acids, 5-hydroxy-1-naphthoic acid, 5-hydroxy-2-naphthoic acid, 6-hydroxy-2-naphthoic acid, and phenolic derivatives of 1- and 2-methylnaphthalene. The metabolites were isolated by thin-layer and reverse-phase high-pressure liquid chromatography and characterized by the application of UV-visible absorption, 1H nuclear magnetic resonance, and mass spectral techniques. Experiments with [8-14C]2-methylnaphthalene indicated that over a 72-h period, 9.8% of 2-methylnaphthalene was oxidized to metabolic products. The ratio of organic-soluble in water-soluble metabolites at 2 h was 92:8, and at 72 h it was 41:59. Enzymatic treatment of the 48-h aqueous phase with either beta-glucuronidase or arylsulfatase released 60% of the metabolites of 2-methylnaphthalene that were extractable with ethyl acetate. In both cases, the major conjugates released were 5-hydroxy-2-naphthoic acid and 6-hydroxy-2-naphthoic acid. The ratio of the water-soluble glucuronide conjugates to sulfate conjugates was 1:1. Incubation of C. elegans with 2-methylnaphthalene under an 18O2 atmosphere and subsequent mass spectral analysis of 2-hydroxymethylnaphthalene indicated that hydroxylation of the methyl group is catalyzed by a monooxygenase.
Design of Gas Conditioning and Processing Facilities (1982)

ABSTRACT The proper planning and choice of such facilities depends on a number of non-process factors--market/economic, geographical, climate, cultural, political, etc. These determine the optimum output of the facility. The input is determined by the characteristics of the reservoirs supplying raw material for conditioning and processing. These establish boundary conditions within which the process must conform. The engineering calculations therefore must find the optimum path between input and output … and are not independent of these considerations. This paper presents the state of the art of gas plant design and how this relates to the non-process factors. It is necessarily an overview but outlines a plan of attack that should provide maximum profitability.
Markerless motion capture using a single depth sensor (2009)

We present a robust framework for tracking skeleton joints in real-time by using a single time-of-flight depth sensor. The framework is able to remove the background noise inherent in time-of-flight cameras, detect multiple people, and track up to 30 joints of free motion for each person. The approach has several advantages over traditional motion capture, as it is a cheap alternative to magnetic and optical systems, and requires no markers whatsoever. Unlike markerless systems based on RGB cameras [Duetscher et al. 2000; Kehl and Van Gool 2006], our framework yields dependable results at an interactive rate using a single camera.
Supporting Handoff in Asynchronous Collaborative Sensemaking Using Knowledge-Transfer Graphs (2017)

During asynchronous collaborative analysis, handoff of partial findings is challenging because externalizations produced by analysts may not adequately communicate their investigative process. To address this challenge, we developed techniques to automatically capture and help encode tacit aspects of the investigative process based on an analyst's interactions, and streamline explicit authoring of handoff annotations. We designed our techniques to mediate awareness of analysis coverage, support explicit communication of progress and uncertainty with annotation, and implicit communication through playback of investigation histories. To evaluate our techniques, we developed an interactive visual analysis system, KTGraph, that supports an asynchronous investigative document analysis task. We conducted a two-phase user study to characterize a set of handoff strategies and to compare investigative performance with and without our techniques. The results suggest that our techniques promote the use of more effective handoff strategies, help increase an awareness of prior investigative process and insights, as well as improve final investigative outcomes.
Spectrophotometric determination of phenol by flow injection on-line preconcentration with a micro-column containing magnetic microspheres functionalized with Cyanex272 (2012)

A novel magnetic adsorbent, magnetic microsphere functionalized with Cyanex272, has been successfully synthesized via a chemical bonding alkylation method. A flow injection on-line preconcentration, with a micro-column packed with the as-synthesized magnetic adsorbent, coupled with UV-Vis spectrophotometric method was developed for the determination of phenol at a wavelength of 270 nm. Various experimental parameters were optimized as follows: eluent (methanol), sample flow rate (1.4 mL min−1), sample volume (1.4 mL), sample pH (5.0), and eluent flow rate (2.2 mL min−1). Under the optimum conditions, the intra-day and inter-day relative standard deviations were 1.37% and 2.69% (n = 5), respectively. The proposed method has been successfully applied to the determination of phenol in phenol ear drops, compound borax solution, and phenol ointment samples and the accuracy was assessed through recovery experiments.
Gastric cytoprotection by epidermal growth factor (1981)

Abstract This study was designed to compare the gastric cytoprotective effects of epidermal growth factor and prostaglandin E 2 and I 2 in rats and cats treated with aspirin and i.v. histamine or intragastric instillation of HCl solution to develop gastric mucosal lesions. Epidermal growth factor given in nonantisecretory doses prevented dose-dependent aspirin-induced gastric ulcers, and this effect was similar to that obtained with nonantisecretory doses of prostaglandin E 2 or prostaglandin I 2 infused alone or in combination with aspirin did not affect the generation of mucosal prostaglandins, suggesting that its cytoprotective effect was not mediated by mucosal prostaglandins. The formation of aspirin-induced ulcers resulted in a significant reduction in DNA synthesis, and this was brought back to normal levels by the administration of epidermal grow factor or prostaglandins given in nonantisecretory cytoprotective doses. We conclude that epidermal growth factor is capable of protecting gastric mucosa against chemical injury caused by aspirin and this protective action is accompanied by a stimulation of DNA synthesis probably as the consequence of tissue preservation by this agent.
Growth in Tissue Culture of Single-Cell Clones From Grape Stem & Phylloxera Gall (1962)

Information about the behavior of clones of plant tissue of single-cell origin is valuable for our understanding of diseased and normal cell growth. Questions appeared about the variability of the cells in the insect-induced galls. Perhaps only a few diseased cells were responsible for the mass of abnormal, rapidly increasing cells, and the majority of the other cells provided a favorable nutritional and physical environment. A large number of single-cell cultures from the mother callus strains of both the normal grape stem tissue and gall tissue incited by Phylloxera vastatrix Planch, were available for study of cell variability (8). Increase in wet weight of the tissue culture resulted from the cell division and growth of the cellular mass, and indicated the degree of the activity of the tissues. Differences were observed in the fresh weight of the clones after 4 to 5 weeks of growth of both the normal and diseased clones when grown on basal mineral salts, 2.0 % sucrose agar medium, supplemented with coconut milk (CM) and additional growth promoting substances including alpha-naphthaleneacetic acid (NAA), calcium pantothenate, and 2,4-dichlorophenoxyacetic acid (2,4-D). The purpose of this study was to clarify the behavior of the selected clones at different periods of their development, and to compare the growth characteristics of the clones with cell counts and dry weight.
PVC Degradation & Stabilization (2008)

With the global renewal of interest in PVC, this book is well timed, considering that PVC stabilization is the most important aspect of its formulation and performance. Only four books have been published on PVC degradation and stabilization (the last one in the 1980s), and two of them are by the author of this book. Separate chapters review information on chemical structure, PVC manufacturing technology, morphology, degradation by thermal energy, and UV, gamma, and other forms of radiation, mechanodegradation, chemical degradation, analytic methods used in studying of degradative and stabilization processes, stabilization, and effect of PVC and its additives on health, safety and environment. This book contains analysis of all essential papers published until recently on the above subject. It either locates the answers to relevant questions and offers solutions or gives references in which such answers can be found. PVC Degradation and Stabilization is must have for chemists, engineers, scientists, university teachers and students, designers, material scientists, environmental chemists, and lawyers who work with polyvinyl chloride and its additives or have any interest in these products. This book is the one authoritative source on the subject. The first book on this subject since the 1980s. Shows new trends and directions in the manufacture and use of polyvinyl chloride (PVC). Helps lead research and development of successful and responsible application of additives in PVC processing and applications.
The Anatomy of a Hypoxic Operator in Saccharomyces cerevisiae (1998)

Aerobic repression of the hypoxic genes of Saccharomyces cerevisiae is mediated by the DNA-binding protein Rox1 and the Tup1/Ssn6 general repression complex. To determine the DNA sequence requirements for repression, we carried out a mutational analysis of the consensus Rox1-binding site and an analysis of the arrangement of the Rox1 sites into operators in the hypoxic ANB1 gene. We found that single base pair substitutions in the consensus sequence resulted in lower affinities for Rox1, and the decreased affinity of Rox1 for mutant sites correlated with the ability of these sites to repress expression of the hypoxic ANB1 gene. In addition, there was a general but not complete correlation between the strength of repression of a given hypoxic gene and the compliance of the Rox1 sites in that gene to the consensus sequence. An analysis of the ANB1 operators revealed that the two Rox1 sites within an operator acted synergistically in vivo, but that Rox1 did not bind cooperatively in vitro, suggesting the presence of a higher order repression complex in the cell. In addition, the spacing or helical phasing of the Rox1 sites was not important in repression. The differential repression by the two operators of the ANB1 gene was found to be due partly to the location of the operators and partly to the sequences between the two Rox1-binding sites in each. Finally, while Rox1 repression requires the Tup1/Ssn6 general repression complex and this complex has been proposed to require the aminoterminal regions of histones H3 and H4 for full repression of a number of genes, we found that these regions were dispensable for ANB1 repression and the repression of two other hypoxic genes.
Electroluminescence Gray Scale Display Driving Method and Circuit (2007)

为个人计算机的颜色终端的增加的使用提起了一个要求因为录像图适配器(VGA ) 格式面板显示。自从仅仅单色(ZnS：Mn ) 合适的尺寸和速度的电镀物品光(EL ) 显示是可得到的，颜色的缺乏不得不被灰度首先代替。有二个基本开车方法在薄电影的 EL 显示完成灰度：脉搏振幅调整(PAM ) 方法和脉搏宽度调整(PWM ) 方法。但是有二个传统的方法的严肃的劣势。为以前的方法，高电压 PAM IC 太昂贵，不能生产灰度 EL 显示 in bulks，司机集成电路(IC ) 是复杂的。尽管 PWM 方法有好灰度显示质量，硬件实现是太复杂的。挑战能有效地被解决的宽度和脉搏的振幅能与并且同时被调制并且同时的一个新开车方法被介绍。
Lactobacillus fermentum IM12 attenuates inflammation in mice by inhibiting NF-κB-STAT3 signalling pathway (2017)

In the present study, we isolated Lactobacillus fermentum IM12 from human gut microbiota, which strongly inhibited interleukin (IL)-6 expression and STAT3 activation in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages, and examined its anti-inflammatory effect in mice with carrageenan-induced hind-paw oedema (CIE) or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis (TIC). Oral administration of IM12 (0.2×10<sup>9</sup>, 1×10<sup>9</sup> or 5×10<sup>9</sup> cfu/mouse, once a day for 3 days) in mice with CIE significantly suppressed the increase of oedema volume and thickness, as well as myeloperoxidase activity and IL-6, IL-17, NO, and prostaglandin E2 levels in the carrageenan-stimulated paw. Treatment with IM12 (1×10<sup>9</sup> cfu/mouse, once a day for 3 days) in mice with TIC significantly suppressed colon shortening, and myeloperoxidase activity and IL-6 and IL-17 levels. Treatment with IM12 in mice with CIE or TIC also suppressed the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, as well as activation of nuclear factor kappa beta (NF-κB) and signal transducer and activator of transcription 3 (STAT3). Furthermore, IM12 significantly inhibited the expression of iNOS, and COX-2, as well as activation of NF-κB in LPS-stimulated mouse peritoneal macrophages. The inflammatory effect of heat-inactivated IM12 was significantly different to that of live IM12 in mice with TIC, although anti-inflammatory effect of IM12 was reduced by heat treatment. Based on these findings, IM12 may attenuate inflammation by inhibiting NF-κB-STAT3 signalling pathway.
Multi-Level Interactions between the Nuclear Receptor TRα1 and the WNT Effectors β-Catenin/Tcf4 in the Intestinal Epithelium (2012)

Intestinal homeostasis results from complex cross-regulation of signaling pathways; their alteration induces intestinal tumorigenesis. Previously, we found that the thyroid hormone nuclear receptor TRα1 activates and synergizes with the WNT pathway, inducing crypt cell proliferation and promoting tumorigenesis. Here, we investigated the mechanisms and implications of the cross-regulation between these two pathways in gut tumorigenesis in vivo and in vitro. We analyzed TRα1 and WNT target gene expression in healthy mucosae and tumors from mice overexpressing TRα1 in the intestinal epithelium in a WNT-activated genetic background (vil-TRα1/Apc mice). Interestingly, increased levels of β-catenin/Tcf4 complex in tumors from vil-TRα1/Apc mice blocked TRα1 transcriptional activity. This observation was confirmed in Caco2 cells, in which TRα1 functionality on a luciferase reporter-assay was reduced by the overexpression of β-catenin/Tcf4. Moreover, TRα1 physically interacted with β-catenin/Tcf4 in the nuclei of these cells. Using molecular approaches, we demonstrated that the binding of TRα1 to its DNA target sequences within the tumors was impaired, while it was newly recruited to WNT target genes. In conclusion, our observations strongly suggest that increased β-catenin/Tcf4 levels i) correlated with reduced TRα1 transcriptional activity on its target genes and, ii) were likely responsible for the shift of TRα1 binding on WNT targets. Together, these data suggest a novel mechanism for the tumor-promoting activity of the TRα1 nuclear receptor.