gebhart/patrepeval huggingface dataset:
Validation of MAF biomarker for response prediction to adjuvant bisphosphonates in 2 clinical trials: AZURE and NSABP-B34. (2020)

513 Background: An Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis indicates that adjuvant bisphosphonates increase time to bone recurrence and survival in postmenopausal breast cancer patients, but results of individual trials have been inconclusive. Retrospective analyses of AZURE, a trial of adjuvant zoledronic acid, showed MAF (a transcription factor of the AP-1 family) amplification status predicted bisphosphonate benefit independently of menopause for invasive disease-free survival (IDFS) and overall survival (OS). Validation of MAF amplification status as a potential companion diagnostic for adjuvant bisphosphonates was confirmed using NSABP-B34 specimens. Methods: The randomized, placebo-controlled NSABP B-34 study of women with stage 1-3 breast cancer were assigned to adjuvant systemic therapy plus oral clodronate 1600 mg daily or placebo for 3 years. The primary endpoint was disease-free survival (DFS) with overall survival (OS) as a secondary outcome. MAF amplification was assessed by fluorescence in-situ hybridization on anonymized sections of breast tumor tissue in all patients with tumor samples and performed in a laboratory blind to treatment assignment. Protocol and analysis plans were pre-specified. Disease outcomes were analysed using intention to treat principles. Results: 2496 B-34 patients contributed tumor samples (from 2001-2004), of whom 1883 (75%) were evaluable (947 placebo and 936 clodronate). 1515 (80%) tumors were MAF negative (766 placebo and 749 clodronate) and 368 were MAF positive. At median follow-up of 108 months, MAF was prognostic for DFS, OS and bone-metastasis-free survival in the control group (MAF-positive vs MAF-negative: HRDFS=1·39, 95%CI 1·01-1·92; p=0.045; HROS=1·59, 95%CI 1·08-2·33; p=0.018; HRBM=2·03, 95%CI 1·13-3·68; p=0.016). In patients with MAF-negative tumors, clodronate gave higher DFS and OS than controls at 60 months (HRDFS=0·70, 95%CI 0·51-0·94; p=0.020 and HROS=0·59, 95%CI 0·37-0·93; p=0.024), the latter maintained through follow-up (HROS=0·74, 95%CI 0·54-1.00; p=0.047), but not in patients with MAF-positive tumors - consistent with previous AZURE results. Conclusions: MAF benefit prediction from adjuvant bisphosphonates was confirmed using specimens from 2 randomized clinical trials (AZURE and NSABP-B-34) conducted and analyzed in similar manner using the same validated tests and clinical endpoints. These results are evidence towards introducing MAF testing into clinical practice.
Mass Spectrometry of Human Leukocyte Antigen Class I Peptidomes Reveals Strong Effects of Protein Abundance and Turnover on Antigen Presentation (2015)

HLA class I molecules reflect the health state of cells to cytotoxic T cells by presenting a repertoire of endogenously derived peptides. However, the extent to which the proteome shapes the peptidome is still largely unknown. Here we present a high-throughput mass-spectrometry-based workflow that allows stringent and accurate identification of thousands of such peptides and direct determination of binding motifs. Applying the workflow to seven cancer cell lines and primary cells, yielded more than 22,000 unique HLA peptides across different allelic binding specificities. By computing a score representing the HLA-I sampling density, we show a strong link between protein abundance and HLA-presentation (p < 0.0001). When analyzing overpresented proteins - those with at least fivefold higher density score than expected for their abundance - we noticed that they are degraded almost 3 h faster than similar but nonpresented proteins (top 20% abundance class; median half-life 20.8h versus 23.6h, p < 0.0001). This validates protein degradation as an important factor for HLA presentation. Ribosomal, mitochondrial respiratory chain, and nucleosomal proteins are particularly well presented. Taking a set of proteins associated with cancer, we compared the predicted immunogenicity of previously validated T-cell epitopes with other peptides from these proteins in our data set. The validated epitopes indeed tend to have higher immunogenic scores than the other detected HLA peptides. Remarkably, we identified five mutated peptides from a human colon cancer cell line, which have very recently been predicted to be HLA-I binders. Altogether, we demonstrate the usefulness of combining MS-analysis with immunogenesis prediction for identifying, ranking, and selecting peptides for therapeutic use.
Inhibitory effects of the tyrosine kinase inhibitor genistein on mammalian DNA topoisomerase II. (1989)

Tyrosine phosphorylation plays a crucial role in cell proliferation and cell transformation which suggests that tyrosine kinase-specific inhibitors might be used as anticancer agents. When the cytotoxic effect of the potent tyrosine kinase inhibitor genistein on various cell lines was studied, we observed that 9-hydroxyellipticine-resistant Chinese hamster lung cells (DC-3F/9-OH-E) were markedly more resistant to genistein than the parental cell line (DC-3F). The DC-3F/9-OH-E cells have been shown to have an altered DNA topoisomerase II activity. We therefore examined the effects of genistein on DNA topoisomerase II-related activities of nuclear extracts from DC-3F cells as well as on purified DNA topoisomerase II from calf thymus. Our results show that genistein (a) inhibits the decatenation activity of DNA topoisomerase II and (b) stimulates DNA topoisomerase II-mediated double strand breaks in pBR322 DNA on sites different from those of 4'-(9-acridinylamino)methanesulfon-m-anisidide, etoposide, and 2-methyl-9-hydroxyellipticinium. Structure-activity studies with six chemically related compounds show that only genistein has an effect on the cleavage activity of DNA topoisomerase II in the concentration range studied. Finally, genistein treatment of DC-3F cells results in the occurrence of protein-linked DNA strand breaks as shown by DNA filter elution. Viscometric (lengthening) studies demonstrate that genistein is not a DNA intercalator. Genistein is therefore an interesting compound because it induces cleavable complexes without intercalation. Taken together, our results show that genistein is an inhibitor of both protein tyrosine kinases and mammalian DNA topoisomerase II. This could be accounted for by the sharing of a common structure sequence between the two proteins at the ATP binding site.
Sampling requirements for Volterra system identification (1996)

Volterra systems generally produce-due to nonlinearity-an output signal with a higher frequency range when compared with the input signal. Hence, it seems necessary to sample the input and output signals at twice the maximum frequency of the output signal. The article shows that it is sufficient to sample at twice the maximum frequency of the input signal. A discrete-time Volterra system also produces the additional frequency components that appear-due to aliasing-at the sampled output of a continuous-time Volterra system with an equivalent transfer function.
90Y-DOTA-hLL2: an agent for radioimmunotherapy of non-Hodgkin's lymphoma. (2003)

(90)Y-hLL2 prepared with the DOTA chelate represents an improved agent for radioimmunotherapy of non-Hodgkin's lymphoma, with an in vivo model demonstrating a large reduction in bone-deposited yttrium, compared with (90)Y-hLL2 agents prepared with open-chain DTPA-type chelating agents. Dosimetry suggests that this benefit will result in a substantial toxicologic advantage for a DOTA-based hLL2 conjugate.
Measurement of the Angular Distribution of Light Scattered from a Glass Fiber Optical Waveguide (1972)

This paper reports the measurement of the angular distribution of light scattered from a low-loss fiber at 1.06 microm and 0.633 microm. In addition to Rayleigh scattering, a previously undetected, near-forward scattering peak was observed. The new peak is shown to be consistent with scattering by narrow dielectric filaments aligned with the axis. The total scattering loss rate at 0.633 microm is ~10 dB/km, about (1/4) of which is due to the near-forward peak. The total scattering loss rate at 1.06 microm is ~1 dB/km.
Location of a new encephalitogenic epitope (residues 43 to 64) in proteolipid protein that induces relapsing experimental autoimmune encephalomyelitis in PL/J and (SJL x PL)F1 mice (1991)

Synthetic peptides of proteolipid protein (PLP) were screened for their ability to induce experimental autoimmune encephalomyelitis (EAE) in SJL/J, PL/J, and (SJL x PL)F1 mice, and T cell lines were selected by stimulation of lymph node cells with PLP peptides. PLP 141-151 was found to be less encephalitogenic in SJL/J mice than PLP 139-151, due to deletion of two amino acids from the amino-terminal end. PLP 139-151 immunization induced relapsing EAE in SJL/J and F1 mice but not PL/J mice. In contrast, PLP 43-64 induced relapsing EAE in PL/J and F1 mice but not SJL/J mice. F1 T cell lines specific for either PLP 43-64 or PLP 139-151 adoptively transferred demyelinating EAE to naive F1 recipients. Haplotypes H-2s and H-2u appear to be immunologically co-dominant in F1 mice in the PLP EAE system, which differs from the H-2u dominance in F1 mice in the myelin basic protein EAE system. The identification of a PLP peptide that is encephalitogenic in PL/J mice, in addition to the previous demonstration of PLP peptides that are encephalitogenic for SWR mice (PLP 103-116) and SJL/J mice (PLP 139-151), lends support to a role for PLP as a target Ag in autoimmune demyelinating diseases.
The Genotype of the Calcium/Calmodulin-Dependent Protein Kinase Gene ( CCaMK ) Determines Bacterial Community Diversity in Rice Roots under Paddy and Upland Field Conditions (2011)

The effects of the Oryza sativa calcium/calmodulin-dependent protein kinase OsCCaMK genotype (dominant homozygous [D], heterozygous [H], recessive homozygous [R]) on rice root-associated bacteria, including endophytes and epiphytes, were examined by using a Tos17 rice mutant line under paddy and upland field conditions. Roots were sampled at the flowering stage and were subjected to clone library analyses. The relative abundance of Alphaproteobacteria was noticeably decreased in R plants under both paddy and upland conditions (0.8% and 3.0%, respectively) relative to those in D plants (10.3% and 17.4%, respectively). Population shifts of the Sphingomonadales and Rhizobiales were mainly responsible for this low abundance in R plants. The abundance of Anaerolineae (Chloroflexi) and Clostridia (Firmicutes) was increased in R plants under paddy conditions. The abundance of a subpopulation of Actinobacteria (Saccharothrix spp. and unclassified Actinosynnemataceae) was increased in R plants under upland conditions. Principal coordinate analysis revealed unidirectional community shifts in relation to OsCCaMK gene dosage under both conditions. In addition, shoot length, tiller number, and plant weight decreased as the OsCCaMK gene dosage decreased under upland conditions. These results suggest significant impacts of OsCCaMK on both the diversity of root-associated bacteria and rice plant growth under both paddy and upland field conditions.
A Massively Parallel Algorithm for Compact Finite Difference Schemes (1994)

A compact scheme is a discretization scheme that is advantageous in obtaining highly accurate solutions. However, the resulting systems from compact schemes are tridiagonal systems that are difficult to solve efficiently on parallel computers. Considering the almost symmetric Toeplitz structure, a parallel algorithm, simple parallel prefix (SPP), is proposed. The SPP algorithm consists of prefix communications and AXPY computations. Both the computation and the communication can be truncated without degrading the accuracy when the system is diagonally dominant. A formal accuracy study has been conducted to provide a simple truncation formula. Experimental results have been measured on a MasPar MP-1 SIMD machine and on a Cray 2 vector machine. Experimental results show that the simple parallel prefix algorithm is a good algorithm for symmetric, almost symmetric Toeplitz tridiagonal systems and for the compact scheme on high-performance computers.
Primary and secondary structure of the 18S ribosomal RNA of the bird spider Eurypelma californica and evolutionary relationships among eukaryotic phyla (1988)

The primary structure of the 18S rRNA of the bird spider Eurypelma californica has been determined in the framework of a study of metazoan phylogeny on the basis of ribosomal RNA structure. A secondary-structure model was derived by comparison of the sequence with that of 43 other eukaryotic small-ribosomal-subunit RNA sequences presently available. This comparison allows a rather detailed secondary-structure pattern to be postulated for a eukaryote-specific area of highly variable sequence and length for which no consensus model has hitherto been attained. A dendrogram, reflecting evolutionary relationships among the 40 eukaryotic species of known 18S rRNA structure, was constructed by a matrix method selecting the best-fitting tree on the basis of a least-squares criterion. The tree shows an early divergence of a microsporidium, an euglenoid, kinetoplastids and a slime mold. Among the remaining species, two main clusters are distinguishable, one comprising the Ciliata, the other comprising Metazoa, green plants, fungi and several protists. Among the Metazoa, the three phyla presently investigated, viz. Chordata, Arthropoda and Nemathelminthes, are distinguishable as three separate lines of descent.
Efalizumab in the Treatment of Psoriasis (2006)

Currently, more than 3,500 patients have received efalizumab in clinical trials. Efalizumab may be an important treatment option for dermatologists seeking to provide a well-tolerated and effective treatment modality for patients with moderate to severe chronic plaque psoriasis.
Inhibition of survivin expression by small interfering RNA (siRNA) in brain tumor cell lines. (2005)

63 Survivin, a member of inhibitor of apoptosis gene (IAP) family, has been proposed as a promising target for new anticancer interventions. Here we report an application of RNA interference with small interfering RNA (siRNA) of survivin to human brain tumor cell lines. The purposes of this study are to investigate the ability and biological effects of siRNA induced inhibition of survivin, and to determine the potentiality of survivin siRNA as a new therapeutic tool in brain tumors. The survivin mRNA expression was measured by real-time RT-PCR in 7 brain tumor cell lines (Daoy, T98G, U118MG, U87MG, A172, IMR32, SH-SY5Y), and one lung adenocarcinoma cell line A549 as a positive control. Three brain tumor cell lines including Daoy (medulloblastoma), U87MG (glioblastoma cell line with wild type p53) and A172 (glioblastoma cell line with mutant p53) were transfected with siRNA oligonucleotides of survivin. Survivin mRNA and protein expressions were measured by real-time RT-PCR and Western blot analysis after 24, 48 and 72 hours of treatment with survivin siRNA, and then compared to nonsense siRNA treated cells. The effects on cytotoxicity and induction of apoptosis were assessed with MTT assay and FACS analysis using Annexin V, before and after treatment with survivin siRNA. High survivin expression was detected in all 7 brain tumor cell lines normalized with A549. After 48 hours of treatment with siRNA of survivin, survivin mRNA level was reduced by 39, 65 and 77% in U87MG, A172 and Daoy cell line, respectively, and protein expression was reduced by 30% in all 3 cell lines. Knockdown of survivin by siRNA induced 32, 32 and 38% of cell death in U87MG, A172 and Daoy cell line, respectively, after 72 hrs of treatment with siRNA of survivin. Knockdown of survivin by siRNA induced 5% of apoptosis in U87MG after 24 hrs of transfection with siRNA of survivin. The effect of siRNA was independent of p53 gene mutation. Our findings suggest that survivin may play an important role in oncogenesis of brain tumors, and survivin-specific siRNA could be a selective therapeutic tool to kill medulloblastoma and glioblastoma cells regardless of the presence or absence of wild-type p53 genes.
Restriction endonuclease fingerprinting (REF): a sensitive method for screening mutations in long, contiguous segments of DNA. (1995)

Restriction endonuclease fingerprinting (REF) is a modification of single-strand confirmation polymorphism (SSCP) that was developed to detect the presence of essentially all mutations in a 1-kb segment. To test REF, a 1-kb segment of the human factor IX gene was amplified with PCR and digested with each of five groups of restriction endonucleases. The endonucleases in each group were chosen so that the average size of the fragments was about 150 bp. After separate digestions, the products were mixed, 5' end-labeled with T4 polynucleotide kinase, denatured and electrophoresed under nondenaturing conditions. Each lane screened 1 kb and typically contained 68 segments (6.8 fragments per average digestion x 5 digestions x 2 strands). REF was performed with 5.6% polyacrylamide and 7.5% GeneAmp at temperatures of either 23 degrees or 8 degrees C. Point mutations resulted in the gain or loss of a restriction site in 21% of 24 test mutations (informative restriction component). In cases in which the restriction component was not informative, mutations were detected if any of the five mutation-containing restriction fragments (producing 10 single-stranded segments) displayed abnormal mobility (SSCP component). The average efficiency per single-stranded segment of the SSCP component for the 24 point mutations ranged from 49% for polyacrylamide at 23 degrees C to 68% with GeneAmp at 8 degrees C. REF detected 96% of the mutations with polyacrylamide at 23 degrees C and 100% with GeneAmp at 23 degrees or 8 degrees C. GeneAmp at 23 degrees and 8 degrees C also detected 100% of a subsequent blinded sample that contained normal controls and 27 different point mutations.(ABSTRACT TRUNCATED AT 250 WORDS)
Structural properties and surface characteristics on aluminum oxide powders (2009)

a-Al2O3 is widely used and studied as high temperature structural material, electronic packaging, corrosion resistance ceramics and translucent ceramics. The surface state of a-Al2O3 powders cannot be regarded as a-Al2O3 but a hydrated state, and that the nature of this hydrate cannot be considered universal among different a-Al2O3, even produced by the same production method. One of these reasons is that water can be incorporated in the a-Al2O3 crystal structure resulting in the formation of aluminum hydroxides such as gibbsite. Although much research has shed light on the Al2O3-water interface and charging of a-Al2O3 surfaces, there is still much that we need to better understand a-Al2O3 structural property and surface characteristics. In this paper, general view of crystal-structural properties, manufacturing methods of high purity a-Al2O3, and surface characteristics on a-Al2O3 powders are introduced. Table 1: Soda impurity level required for different applications
Free radicals, oxidative stress, and antioxidants : pathological and physiological significance (1998)

Mechanisms Involved in Free Radical Reactions Iron in Free Radical Reactions and Antioxidant Protection J.M.C. Gutteridge. Non-Chelation Dependent Redox Actions of Desferrioxamine B.Z. Zhu, et al. The Effects of Oxidative Stress on the Redox System of the Human Erythrocyte I.H. Ogus, et al. Free Radicals in Health and Disease: Reactive Oxygen Species (ROS) and Alteration of F0F1-ATP Synthase in Aging and Liver Regeneration F. Guerrieri, et al. Free Radicals and Antioxidants in Physical Exercise J. Vina, et al. The Role of Free Radical Mediation of Protein Oxidation in Aging and Disease E.R. Stadtman. Antioxidants: Mechanisms of Antioxidant Action E. Cadenas. Repair Systems and Inducible Defenses Against Oxidant Stress K.J.A. Davies. The 'Push-Pull Mechanism': Protection Against Site-Specific and Transition Metal-Mediated Damage M. Chevion, et al. Methodology: EPR Spectroscopy of Phenolic Plant Antioxidants W. Bors, et al. Clastogenic Factors as Biomarkers of Oxidative Stress. Their Usefulness for Evaluation of the Efficacy of Antioxidant Treatments I. Emeritt. Chemiluminescence Measurements for the Detection of Free Radical Species A.S. Yalc, et al. 21 Additional Articles. Index.
Urodynamic evaluation of sacral neuromodulation for urge urinary incontinence (2007)

These urodynamic results show a statistically significant improvement in FSF and MFV in patients with UI with or with no DO after SNM. Although there was a urodynamic and clinical improvement in both groups, patients with UI but no DO are at least as successful as patients with UI and DO. Therefore in patients with UI, DO should not be a prerequisite selection criterion for using SNM.
Improved cardiac function in infarcted mice after treatment with pluripotent embryonic stem cells (2006)

Because pluripotent embryonic stem cells (ESCs) are able to differentiate into any tissue, they are attractive agents for tissue regeneration. Although improvement of cardiac function has been observed after transplantation of pluripotent ESCs, the extent to which these effects reflect ESC-mediated remuscularization, revascularization, or paracrine mechanisms is unknown. Moreover, because ESCs may generate teratomas, the ability to predict the outcome of cellular differentiation, especially when transplanting pluripotent ESCs, is essential; conversely, a requirement to use predifferentiated ESCs would limit their application to highly characterized subsets that are available in limited numbers. In the experiments reported here, we transplanted low numbers of two murine ESC lines, respectively engineered to express a beta-galactosidase gene from either a constitutive (elongation factor) or a cardiac-specific (alpha-myosin heavy chain) promoter, into infarcted mouse myocardium. Although ESC-derived tumors formed within the pericardial space in 21% of injected hearts, lacZ histochemistry revealed that engraftment of ESC was restricted to the ischemic myocardium. Echocardiographic monitoring of ESC-injected hearts that did not form tumors revealed functional improvements by 4 weeks postinfarction, including significant increases in ejection fraction, circumferential fiber shortening velocity, and peak mitral blood flow velocity. These experiments indicate that the infarcted myocardial environment can support engraftment and cardiomyogenic differentiation of pluripotent ESCs, concomitant with partial functional recovery.
Impact of Parameter Variations on Circuits and Microarchitecture (2006)

Parameter variations, which are increasing along with advances in process technologies, affect both timing and power. Variability must be considered at both the circuit and microarchitectural design levels to keep pace with performance scaling and to keep power consumption within reasonable limits. This article presents an overview of the main sources of variability and surveys variation-tolerant circuit and microarchitectural approaches