gebhart/patrepeval huggingface dataset:
Biology of premature ageing in survivors of cancer (2017)

Over 30 million cancer survivors exist worldwide. Survivors have an earlier onset and higher incidence of chronic comorbidities, including endocrinopathies, cardiac dysfunction, osteoporosis, pulmonary fibrosis, secondary cancers and frailty than the general population; however, the fundamental basis of these changes at the cellular level is unknown. An electronic search was performed on Embase, Medline In-Process & Other Non-Indexed Citations, and the Cochrane Central Register of Controlled Trials. Original articles addressing the cellular biology of ageing and/or the mechanisms of cancer therapies similar to ageing mechanisms were included, and references of these articles were reviewed for further search. We found multiple biological process of ageing at the cellular level and their association with cancer therapies, as well as with clinical effects. The direct effects of various chemotherapies and radiation on telomere length, senescent cells, epigenetic modifications and microRNA were found. We review the effects of cancer therapies on recognised hallmarks of ageing. Long-term comorbidities seen in cancer survivors mimic the phenotypes of ageing and likely result from the interaction between therapeutic exposures and the underlying biology of ageing. Long-term follow-up of cancer survivors and research on prevention strategies should be pursued to increase the length and quality of life among the growing population of cancer survivors.
Gene-for-Genes Interactions Between CottonRGenes andXanthomonas campestrispv.malvacearum avrGenes (1993)

Six plasmid-borne avirulence (avr) genes were previously cloned from strain XcmH of the cotton pathogen, Xanthomonas campestris pv. malvacearum. We have now localized all six avr genes on the cloned fragments by subcloning and Tn5-gusA insertional mutagenesis. None of these avr genes appeared to exhibit exclusively gene-for-gene patterns of interactions with cotton R genes, and avrB4 was demonstrated to confer avr gene-for-R genes (plural) avirulence to X. c. pv. malvacearum on congenic cotton lines carrying either of two different resistance loci, B1 or B4. Furthermore, the B1 locus appeared to confer R gene-for-avr genes resistance to cotton against isogenic X. c. pv. malvacearum strains carrying any one of three avr genes: avrB4, avrb6, or avrB102. Restriction enzyme, Southern blot hybridization, and DNA sequence analyses showed that the XcmH avr genes are all highly similar to each other, to avrBs3 and avrBsP from the pepper pathogen X. c. pv. vesicatoria, and to the host-specific virulence gene pthA from the citrus pathogen X. citri. The XcmH avr genes differed primarily in the multiplicity of a tandemly repeated 102-base pair motif within the central portions of the genes, repeated from 14 to 23 times in members of this gene family. The complete nucleotide sequence of avrb6 revealed that it is 97% identical in DNA sequence to avrB4, avrBs3, avrBsP, and pthA and that 62-bp inverted terminal repeats mark the boundaries of homology between avrb6 and all members of this Xanthomonas virulence/avirulence gene family sequenced to date. The terminal 38 bp of both inverted repeats are highly similar to the 38-bp consensus terminal sequence of the Tn3 family of transposons. Up to 11 members of the avr gene family appear to be present in North American strains of X. c. pv. malvacearum, including XcmH. The high level of homology observed among these avr genes and their presence in multiple copies may explain the gene-for-genes interactions and also the observed high frequencies (10(-3) to 10(-4) per locus) of X. c. pv. malvacearum race change mutations. Five spontaneous race change mutants of XcmH suffered avr locus deletions, strongly indicating intergenic recombination as the primary mechanism for generating new races in X. c. pv. malvacearum.
A Tool for Creating and Parallelizing Bioinformatics Pipelines (2007)

Bioinformatics pipelines enable life scientists to effectively analyze biological data through automated multi-step processes constructed by individual programs and databases. The huge amount of data and time consuming computations require effectively parallelized pipelines to provide results within a reasonable time. To reduce researchers' programming burden for pipeline creation and parallelization, we developed the Bioinformatics Pipeline Generation and Parallelization Toolkit (BioGent). A user needs only to create a pipeline definition file that describes the data processing sequence and input/output files. A program termed schedpipe in the BioGent toolkit takes the definition file and executes the designed procedure. Schedpipe automatically parallelizes the pipeline execution by performing independent data processing steps on multiple CPUs, and by decomposing big datasets into small chunks and processing them in parallel. Schedpipe controls program execution on multiple CPUs through a simple application programming interface (API) of the Parallel Job Manager (PJM) library. As a part of the BioGent toolkit, PJM was developed to effectively launch and monitor programs on multiple CPUs using a Message Passing Interface (MPI) protocol. The PJM API can also be used to parallelize other serial programs. A demonstration using PJM for parallelization shows 10% to 50% savings in time compared to an indigenous parallelization through a batch queuing system.
Automated search-model discovery and preparation for structure solution by molecular replacement (2007)

A novel automation pipeline for macromolecular structure solution by molecular replacement is described. There is a special emphasis on the discovery and preparation of a large number of search models, all of which can be passed to the core molecular-replacement programs. For routine molecular-replacement problems, the pipeline automates what a crystallographer might do and its value is simply one of convenience. For more difficult cases, the pipeline aims to discover the particular template structure and model edits required to produce a viable search model and may succeed in finding an efficacious combination that would be missed otherwise. The pipeline is described in detail and a number of examples are given. The examples are chosen to illustrate successes in real crystallography problems and also particular features of the pipeline. It is concluded that exploring a range of search models automatically can be valuable in many cases.
The Optimal Time to Initiate HIV Therapy Under Ordered Health States (2008)

The question of when to initiate HIV treatment is considered the most important question in HIV care today. Benefits of delaying therapy include avoiding the negative side effects and toxicities associated with the drugs, delaying selective pressures that induce the development of resistant strains of the virus, and preserving a limited number of treatment options. On the other hand, the risks of delayed therapy include the possibility of irreversible damage to the immune system, development of AIDS-related complications, and death. We use Markov decision processes to develop the first HIV optimization models that aim to maximize the expected lifetime or quality-adjusted lifetime of a patient. We prove conditions that establish structural properties of the optimal solution and compare them to our data and results. Model solutions, based on clinical data, support a strategy of treating HIV earlier in its course as opposed to recent trends toward treating it later.
Effects of feeding blends of grains naturally contaminated with Fusarium mycotoxins on performance, metabolism, hematology, and immunocompetence of ducklings (2005)

Experiments were conducted to determine the effects of feeding grains naturally contaminated with Fusarium mycotoxins on performance, metabolism, hematology, and immune competence of ducklings. Four hundred sixty-four 1-d-old White Pekin male ducklings were fed starter (0 to 2 wk), grower (3 to 4 wk), and finisher (5 to 6 wk) diets formulated with uncontaminated grains, a low level of contaminated grains, a high level of contaminated grains, or the higher level of contaminated grains + 0.2% polymeric glucomannan mycotoxin adsorbent. Body weight gains, feed consumption, and feed efficiency were not affected by diet. However, consumption of contaminated grains decreased plasma calcium concentrations after 2 wk and plasma uric acid concentrations at the 4-wk assessment point. Mean corpuscular hemoglobin concentrations and hematocrit decreased when ducks were fed contaminated grains for 4 or 6 wk, respectively. In contrast, total numbers of white blood cells and lymphocytes increased transiently in birds fed contaminated grains for 4 wk. The antibody response to sheep red blood cells (CD4+ T cell dependent) and the cell-mediated response to phytohemagglutinin-P (also CD4+ T cell dependent) were not affected by diet, but consumption of contaminated grains for 6 wk decreased the duration of peak cell-mediated response to dinitrochlorobenzene (CD8+ T cell dependent) assessed in a skin test. Feeding grains naturally contaminated with Fusarium mycotoxins, even at levels widely regarded as high, exerted only minor adverse effects on plasma chemistry and hematology of ducklings, and production parameters were unaffected in this avian species. Mycotoxin-contaminated feeds may, however, render these animals susceptible to infectious agents such as viruses against which the CD8+ T cell provides necessary defence. Glucomannan mycotoxin adsorbent was not effective in preventing alterations caused by Fusarium mycotoxins.
The pathogenesis of rheumatoid arthritis: pivotal cytokines involved in bone degradation and inflammation. (2002)

Proinflammatory cytokines, notably interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), play an important role in initiating and perpetuating inflammatory and destructive processes in the rheumatoid joint. These cytokines regulate many nuclear factor kappaB inducible genes that control expression of other cytokines, cell adhesion molecules, immunoregulatory molecules, and proinflammatory mediators. The expression of cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) and thereby production of prostaglandins (PG) and NO are regulated by cytokines. PGE2 and NO further promote inflammation and likely participate in destructive mechanisms in the rheumatoid joint. In some experimental systems, the effects of IL-1 and TNF-alpha appear synergistic, and correspondingly, concomitant inhibition of both cytokines provides greater than additive antiarthritic effects. Although the actions of IL-1 and TNF-alpha show a large degree of overlap, some differences have been observed in animal models. However, in patients with active rheumatoid arthritis, blockade of either cytokine results in clinical improvement and less radiographic progression.
Study of Expression of Ku70 and NHEJ in CML Cells (2008)

Abstract Objective FThe DNA double strand breaks (DSB) in mammalian cells are predominantly repaired by a process called non-homologous DNA end joining (NHEJ). Ku70 played a pivotal role in NHEJ pathway. As a common hematological malignant disease with unique chromosomal translocation t (9;22), chronic myeloid leukemia (CML) can be considered as a paradigm for neoplasias that evolve through a multi-step process. As we reported before, protein Ku70 expressed significantly higher in CML than in normal BM cells. Meanwhile, its expression level in blast phase was markedly higher than that in chronic phase. The present study furthermore aims to investigate the expression of the gene Ku70 in CML cells at different clinical stage and reveal the correlation among the expression of the gene Ku70, the protein Ku70 and BCR-ABL in cells of CML. The NHEJ efficiency to repair DSB in CML was also investigated. Methods: Bone marrow cells were collected from 24 cases of normal adults and 27 cases of de novo diagnosed CML patients. 15 CML patients were in chronic phase and 12 in blast phase. The expression of gene Ku70 was detected by RT-PCR and RQ-RT-PCR. The fusion gene BCR-ABL was detected by TaqMan probe Real Time PCR, using ABL as the internal control. Nucleic extracted proteins were used to determine NHEJ efficiency by an in vitro end-ligation system. Results: The mean level of NHEJ activity of normal BM cells and CML cells were 18.6±13.1% vs 24.8±14.9%, .024. The gene Ku 70 expression in normal BM cells and CML cells were 31.08±8.41 vs 544.63±1185.71 copies/10,000 β-Actin copies, P=0.039. gene Ku 70 expressed significantly higher in blast phase (1103.31±1645.62 copies/10,000 β-Actin copies, P&amp;lt;0.01). There were positive correlations of BCR-ABL when compared with the expression of the gene Ku70 (r=0.573 P=0.002) and with the protein Ku70 (r=0.705 P&amp;lt;0.001) in CML cells. There was also significantly correlations between the expression of the gene Ku70 and the protein Ku70 (r=0. 808, P&amp;lt;0.001). Conclusions: The gene and protein of Ku70 were expressed significantly higher in CML than in normal BM cells with NHEJ activity was also enhanced in CML cells. Meanwhile, Ku70 expression level in acute phase was markedly higher than that in chronic phase. There were significantly correlations among the expression of fusion gene BCR-ABL, the gene Ku70 and the protein Ku70 in cells of CML This Study illustrates DNA instability in CML cells which was mainly damaged by DSB, and this kind of DNA damage was repaired by NHEJ pathway predominantly. NHEJ pathway plays an important role in disease progression of CML.
Reformulation of the relativistic conversion between coordinate time and atomic time (1975)

The relativistic conversion between coordinate time and atomic time is reformulated to allow simpler time calculations relating analysis in solar system barycentric coordinates (using coordinate time) with earth-fixed observations (measuring 'earth-bound' proper time or atomic time). After an interpretation in terms of relatively well-known concepts, this simplified formulation, which has a rate accuracy of about 10 to the minus 15th, is used to explain the conventions required in the synchronization of a worldwide clock network and to analyze two synchronization techniques - portable clocks and radio interferometry. Finally, pertinent experimental tests of relativity are briefly discussed in terms of the reformulated time conversion.
Disulphide interchange reactions involving cyclocystine and their relevance to problems of α-keratin structure (1968)

Research Article| July 01 1968 Disulphide interchange reactions involving cyclocystine and their relevance to problems of α-keratin structure H Lindley; H Lindley 1Division of Protein Chemistry, Commonwealth Scientific and Industrial Research Organisation, Wool Research Laboratories, Parkville, Melbourne, Vic. 3052, Australia Search for other works by this author on: This Site PubMed Google Scholar T Haylett T Haylett 1Division of Protein Chemistry, Commonwealth Scientific and Industrial Research Organisation, Wool Research Laboratories, Parkville, Melbourne, Vic. 3052, Australia Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1968) 108 (4): 701–703. https://doi.org/10.1042/bj1080701 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation H Lindley, T Haylett; Disulphide interchange reactions involving cyclocystine and their relevance to problems of α-keratin structure. Biochem J 1 July 1968; 108 (4): 701–703. doi: https://doi.org/10.1042/bj1080701 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1968 The Biochemical Society1968 Article PDF first page preview Close Modal You do not currently have access to this content.
THE NF-κB AND IκB PROTEINS: New Discoveries and Insights (1996)

The transcription factor NF-kappa B has attracted widespread attention among researchers in many fields based on the following: its unusual and rapid regulation, the wide range of genes that it controls, its central role in immunological processes, the complexity of its subunits, and its apparent involvement in several diseases. A primary level of control for NF-kappa B is through interactions with an inhibitor protein called I kappa B. Recent evidence confirms the existence of multiple forms of I kappa B that appear to regulate NF-kappa B by distinct mechanisms. NF-kappa B can be activated by exposure of cells to LPS or inflammatory cytokines such as TNF or IL-1, viral infection or expression of certain viral gene products, UV irradiation, B or T cell activation, and by other physiological and nonphysiological stimuli. Activation of NF-kappa B to move into the nucleus is controlled by the targeted phosphorylation and subsequent degradation of I kappa B. Exciting new research has elaborated several important and unexpected findings that explain mechanisms involved in the activation of NF-kappa B. In the nucleus, NF-kappa B dimers bind to target DNA elements and activate transcription of genes encoding proteins involved with immune or inflammation responses and with cell growth control. Recent data provide evidence that NF-kappa B is constitutively active in several cell types, potentially playing unexpected roles in regulation of gene expression. In addition to advances in describing the mechanisms of NF-kappa B activation, excitement in NF-kappa B research has been generated by the first report of a crystal structure for one form of NF-kappa B, the first gene knockout studies for different forms of NF-kB and of I kappa B, and the implications for therapies of diseases thought to involve the inappropriate activation of NF-kappa B.
Are Commercial Patient Education Materials Right For You? (1987)

SUSAN D. FOSTER. R.N., M.S., is director of pediatric nursing at Grady Memorial Hospital in Atlanta, Georgia
Inhibition of cigarette smoke-mediated lung tumorigenesis in A/J mice by dietary berries (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

3895 

Cigarette smoke contains approx. 100 carcinogens, co-carcinogens and mutagens. Polycyclic aromatic hydrocarbons (PAHs), aromatic amines and tobacco-specific nitrosamines such as NNK have received most attention in relation to tobacco lung carcinogenesis, although other smoke constituents like catechols and aldehydes may be equally relevant since they are present in smoke at much higher levels. Our previous studies in rodents have shown that smoke-associated adducts in respiratory tissue DNA were unrelated to typical PAHs and aromatic amines, and suggested that free radicals may be involved in their origination. Experimental evidence exists that chemopreventive agents, which inhibited benzo[ a ]pyrene and NNK-induced lung tumorigenesis in A/J mice, failed to reduce cigarette smoke-mediated lung tumor formation. These observations suggest a role of other constituents in tobacco lung carcinogenesis. Data from several laboratories, including our own, show protective effects of berries against oxidative DNA damage, and tumor formation. In the present study, we tested a mixture of berries for their capacity to reduce smoke-mediated lung tumorigenesis. Two groups of female A/J mice (n=40) were maintained on either AIN-93M diet or the same diet supplemented with a mixture of berry powder (0.5% each of strawberries, black raspberries, blackberries and blueberries). After one week, each group was further subdivided into control and smoke-exposed groups, which was exposed to cigarette smoke for six hours per day, five days a week for five months, and then allowed to recover in ambient air for four months. At the termination of the experiment, lungs were excised and evaluated for tumor incidence and multiplicity. The results showed an increase in lung tumor incidence (31% vs. 80%) and multiplicity (0.56 ± 0.24 vs. 1.1±0.25) in smoke-exposed subgroup maintained on AIN-93M diet. In berry-supplemented diet group, the lung tumor incidence (35% vs. 55%) and the tumor multiplicity (0.45 ± 0.15 vs. 0.75 ± 0.18) in smoke-exposed animals were reduced when compared to the sham subgroup. The results clearly suggest a protective effect of dietary berries on the incidence and multiplicity of lung tumor formation in A/J mice by cigarette smoke (Supported from CA-96310).
Molecular Forms of Glucagon-Like Peptide-1 in Human Pancreas and Glucagonomas (1985)

The structure of human preproglucagon, as deduced from nucleotide sequencing of the preproglucagon gene, contains two glucagon-like peptides (GLP-1 and GLP-2) in the portion C-terminal to glucagon. A rabbit antiserum was raised against synthetic GLP-1-(1-19) which had 20% cross-reactivity with synthetic GLP-1 and des-Gly37-GLP-1 amide, two possible forms of the GLP-1 whole molecule, but no significant cross-reactivity with glucagon or other pancreatic peptides. Immunocytochemistry revealed that the distribution of GLP-1-(1-19) immunoreactivity followed that of glucagon-like immunoreactivity in the normal human pancreas and in two human glucagon-secreting pancreatic tumors. Chromatography of human pancreas extracts on Sephadex G-50 gave peaks of cross-reactivity at Kav values of 0.06-0.16, 0.34-0.39, 0.54-0.58 (the elution position of synthetic GLP-1), and 0.64-0.70. The concentration of immunoreactivity in the Kav 0.54-0.58 peak measured by RIA using GLP-1 or des-Gly37-GLP-1 amide as standard was 94 +/- 7 pmol/g (mean +/- SEM), while the total pancreatic glucagon content was 4.8 +/- 0.8 nmol/g. One extract of a human glucagon-secreting pancreatic tumor contained a prominent peak of GLP-1-(1-19) peptide cross-reactivity with properties identical to those of GLP-1 or des-Gly37-GLP-1 amide on gel filtration and reverse phase high pressure liquid chromatography, but another tumor contained a preponderance of cross-reactive forms of greater molecular size. Pretreatment plasma from three patients with radiological and biochemical evidence of glucagon-secreting tumors contained a peak of cross-reactivity with the chromatographic properties of intact GLP-1. The low concentrations of intact GLP-1 in normal pancreas compared with pancreatic glucagon concentrations suggest that the majority of the proglucagon is cleaved in a manner that does not produce GLP-1, as defined by its delimiting pairs of basic amino acid residues.