gebhart/patrepeval huggingface dataset:
Correlation of promoter hypermethylation in hTERT, DAPK and MGMT genes with cervical oncogenesis progression (2009)

DNA hypermethylation occurs during the multistep process of cervical carcinogenesis. We investigated whether the methylation status in the promoter region of a potential oncogene, the human telomerase reverse transcriptase (hTERT), and the tumor suppressor genes death-associated protein kinase (DAPK) and O6-methylguanine DNA methyltransferase (MGMT), were able to distinguish the early from late stages of cervical oncogenesis. The methylation status in the promoter of these genes was analyzed using real-time MethyLight analysis in 115 cervical specimens, including normal, premalignant [atypical squamous epithelial cells (ASCUS), low-grade squamous intraepithelial lesions (LGSIL), high-grade squamous intraepithelial lesions (HGSIL)] and cancer specimens. Clinicopathological parameters (cytology, histology, grade, stage) were compared to the levels of promoter hypermethylation. We found that hTERT, MGMT and DAPK hypermethylation levels were increased during cervical oncogenesis progression. hTERT promoter hypermethylation was able to distinguish normal from cancer (p=0.008), normal from premalignant (p=0.036), as well as premalignant from cervical cancer cases (p=0.003). A significant association was also observed between all three genes and the grade of cervical cancer, with hTERT showing a better association (p<0.0001). Our data suggest that the combination of hTERT, MGMT, DAPK promoter hypermethylation could have a potential function as molecular biomarker of cervical oncogenesis progression.
Clostridium leptum group bacteria abundance and diversity in the fecal microbiota of patients with inflammatory bowel disease: a case–control study in India (2013)

C. leptum numbers and diversity were significantly reduced in both CD and UC suggesting that alterations noted were not specific to one disease. This could contribute to reduced short chain fatty acid production in IBD.
Experimental evidence for the existence of absolute acoustic band gaps in two-dimensional periodic composite media (1998)

International audience
Heart Disease and Stroke Statistics—2011 Update (2010)

Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on disease morbidity and mortality and the risks, quality of care, medical procedures and operations, and costs associated with the management of these diseases in a single document. Indeed, since 1999, the Statistical Update has been cited more than 8700 times in the literature (including citations of all annual versions). In 2009 alone, the various Statistical Updates were cited ≈1600 times (data from ISI Web of Science). In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas. For this year’s edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year and added a new chapter detailing how family history and genetics play a role in cardiovascular disease (CVD) risk. Also, the 2011 Statistical Update is a major source for monitoring both cardiovascular health and disease in the population, with a focus on progress toward achievement of the AHA’s 2020 Impact Goals. Below are a few highlights from this year’s Update.
Pure Red-Cell Aplasia “Epidemic”—Mystery Completely Revealed? (2007)

Starting in 1998, the number of pure red-cell aplasia (PRCA) cases in patients treated with recombinant human erythropoietin (rHuEPO) increased dramatically. Most cases were observed in patients treated with epoetin alfa produced outside the United States. The peak was observed in 2002; since then, the PRCA incidence has declined. Many factors are likely to have contributed to this up-surge. The molecular structure of the various epoetins and patient characteristics do not seem to play a major role. The route of administration holds some importance, because most PRCA patients received rHuEPO subcutaneously. The peak of PRCA cases overlapped with the removal of human serum albumin from the Eprex formulation (Janssen-Pharmaceutica NV, Beerse, Belgium), for which polysorbate 80 and glycine were substituted. Polysorbate 80 may have increased the immunogenicity of Eprex by eliciting the formation of epoetin-containing micelles or by interacting with leachates released by the uncoated rubber stoppers of prefilled syringes. Compared with the previous formulation, the polysorbate 80 formulation has lower stability, making it more susceptible to stress conditions such as insufficient attention to the cold chain. This situation could facilitate protein denaturation or aggregate formation. Uncoated rubber stoppers were replaced with coated stoppers, and the cold chain was reinforced; the Eprex formulation has remained unchanged. Even though the incidence of PRCA returned to very low levels, discriminating the cause-effect relationship of a single action is difficult, given that all occurred with a similar chronology, and that PRCA develops after a relatively long exposure period. Careful observation of future trends of new PRCA cases is thus mandatory.
Cardiac protein kinases: the cardiomyocyte kinome and differential kinase expression in human failing hearts (2015)

This characterization of the spectrum of kinases expressed in cardiomyocytes and the heart (cardiomyocyte and cardiac kinomes) identified novel kinases, some of which are differentially expressed in failing human hearts and could serve as potential therapeutic targets.
Attention to Memory and the Environment: Functional Specialization and Dynamic Competition in Human Posterior Parietal Cortex (2010)

Posterior parietal cortex has been traditionally associated with perceptual attention and sensory-motor processing, but recent studies also indicate a potential role in episodic memory retrieval. Here, we developed a new paradigm to isolate top-down attention-related activity directed to either memory or perceptual information. We demonstrated a robust topographic separation in human posterior parietal cortex associated with searching for task-relevant information in episodic memory or in the environment. Control analyses confirmed that this difference was not dependent on differences in sensory stimulation or eye movements across tasks. Notably, we observed in memory- and perception-related regions a mechanism of reciprocal dynamic competition that was related to behavioral performance. These results provide the first evidence for a double dissociation between parietal networks involved in top-down attention to memory and the environment and support the idea of neural competition between perception and memory.
Tunable Pneumatic Microoptics (2008)

A new class of tunable and actuated microoptical devices is presented: pneumatic microoptics. Using microelectromechanical system fabrication technology extended by the use of polydimethylsiloxane (PDMS) membranes, tunable microlenses, and lens arrays, actuated micromirrors with large tilt angles and tip-tilt piston mirrors have been designed and fabricated. Actuation is by pressure: Gas- or liquid-filled microfluidic cavities are employed to distend the microfabricated PDMS structures which then act as a lens surface or as an actuator for a micromirror. Thermopneumatic actuation is also employed for completely integrated tunable optical systems in which all actuator and optical components are fabricated on-chip. The technology is particularly promising for microsystem applications in which significant movement is required but high voltages or external fields are impractical. [2007-0301].
Spintronics: Fundamentals and applications (2004)

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.
Calcium/calmodulin‐dependent protein kinase II phosphorylates tau at Ser‐262 but only partially inhibits its binding to microtubules (1996)

PHF-tau, which is phosphorylated at 10 Ser/Thr-Pro and 11 non-Ser/Thr-Pro sites, is unable to promote microtubule assembly. Phosphorylation of the non-Ser/Thr-Pro site, Ser-262, is reported to be primarily responsible for this. The identities of kinase(s) responsible for Ser-262 phosphorylation are still to be clarified. In this study we have used the monoclonal antibody 12E8, which recognizes P-Ser-262 and P-Ser-356 on tau, to survey different kinases for their abilities to phosphorylate Ser-262 on human tau 3L (tau410). In decreasing order of effectiveness we found that Ser-262 and Ser-356 phosphorylation can be catalyzed by CaM kinase II >> C-kinase >> GSK-3 approximately = A-kinase >> CK-1. CaM kinase II and C-kinase were shown to phosphorylate both Ser-262 and Ser-356. The binding of tau to taxol-stabilized microtubules was decreased by 35 and 42% after phosphorylation by CaM kinase II and C-kinase, respectively. Of the fraction of tau that bound to microtubules, about 50% was phosphorylated at Ser-262 and Ser-356. These results suggest that Ser-262 and Ser-356 are very good substrates for CaM kinase II but their phosphorylations are not sufficient to achieve maximal inhibition of tau binding to microtubules.
Prediction of screener-induced moire in digital halftone pattern generation (1990)

In the graphic arts, objectionable moire patterns are often observed on films or printed products due to the interaction of various periodic structures of halftone images. A particular type of moire pattern that results from digital halftoning at arbitrary angles and frequencies using a virtual screen function has been studied. A computer program was developed that produces uniform digital halftone patterns using a virtual screen approach and that calculates the corresponding amplitude spectra. It was found that aliasing due to the sampling of the virtual screen causes low frequency components in the amplitude spectrum. Moire patterns with fundamental vector frequencies equal to those of the strong aliased components were observed in halftone images reconstructed on a film recorder. Moire was also observed at frequencies not represented or under represented in the amplitude spectrum. It is shown that this moire effect is due to the additive beating of two or more higher frequency components that differ by the frequency of the observed moire. It is suggested that the non-linearities of the film recording process amplify this effect . The effects on the resulting moire patterns of varying the halftone parameters of dot size, dot shape, screen angle, and screen frequency were examined. In general, the amplitude spectra are complex, indicating many overlapping patterns. Screener induced moire was found to behave in a nearly identical manner to that induced by digital scanning of an existing halftone .
Mitigating Attacks Against Measurement-Based Adaptation Mechanisms in Unstructured Multicast Overlay Networks (2006)

Many multicast overlay networks maintain application-specific performance goals such as bandwidth, latency, jitter and loss rate by dynamically changing the overlay structure using measurement-based adaptation mechanisms. This results in an unstructured overlay where no neighbor selection constraints are imposed. Although such networks provide resilience to benign failures, they are susceptible to attacks conducted by adversaries that compromise overlay nodes. Previous defense solutions proposed to address attacks against overlay networks rely on strong organizational constraints and are not effective for unstructured overlays. In this work, we identify, demonstrate and mitigate insider attacks against measurement-based adaptation mechanisms in unstructured multicast overlay networks. The attacks target the overlay network construction, maintenance, and availability and allow malicious nodes to control significant traffic in the network, facilitating selective forwarding, traffic analysis, and overlay partitioning. We propose techniques to decrease the number of incorrect or unnecessary adaptations by using outlier detection. We demonstrate the attacks and mitigation techniques in the context of a mature, operationally deployed overlay multicast system, ESM, through real-life deployments and emulations conducted on the PlanetLab and DETER testbeds, respectively.
Synthesis, Characterization, andin VitroTesting of Superparamagnetic Iron Oxide Nanoparticles Targeted Using Folic Acid-Conjugated Dendrimers (2008)

Organic-coated superparamagnetic iron oxide nanoparticles (OC-SPIONs) were synthesized and characterized by transmission electron microscopy and X-ray photoelectron spectroscopy. OC-SPIONs were transferred from organic media into water using poly(amidoamine) dendrimers modified with 6-TAMRA fluorescent dye and folic acid molecules. The saturation magnetization of the resulting dendrimer-coated SPIONs (DC-SPIONs) was determined, using a superconducting quantum interference device, to be 60 emu/g Fe versus 90 emu/g Fe for bulk magnetite. Selective targeting of the DC-SPIONs to KB cancer cells in vitro was demonstrated and quantified using two distinct and complementary imaging modalities: UV-visible and X-ray fluorescence; confocal microscopy confirmed internalization. The results were consistent between the uptake distribution quantified by flow cytometry using 6-TAMRA UV-visible fluorescence intensity and the cellular iron content determined using X-ray fluorescence microscopy.
Direct and indirect gene replacements in Aspergillus nidulans. (1985)

We performed three sets of experiments to determine whether cloned DNA fragments can be substituted for homologous regions of the Aspergillus nidulans genome by DNA-mediated transformation. A linear DNA fragment containing a heteromorphic trpC+ allele was used to transform a trpC- strain to trpC+. Blot analysis of DNA from the transformants showed that the heteromorphic allele had replaced the trpC- allele in a minority of the strains. An A. nidulans trpC+ gene was inserted into the argB+ gene, and a linear DNA fragment containing the resultant null argB allele was used to transform a trpC- argB+ strain to trpC+. Approximately 30% of the transformants were simultaneously argB-. The null argB allele had replaced the wild-type allele in a majority of these strains. The A. nidulans SpoC1 C1-C gene was modified by removal of an internal restriction fragment and introduced into a trpC- strain by transformation with a circular plasmid. A transformant containing a tandem duplication of the C1-C region separated by plasmid DNA was self-fertilized, and trpC- progeny were selected. All of these had lost the introduced plasmid DNA sequences, whereas about half had retained the modified C1-C gene and lost the wild-type copy. Thus, it is possible with A. nidulans to replace chromosomal DNA sequences with DNA fragments that have been cloned and modified in vitro by using either one- or two-step procedures similar to those developed for Saccharomyces cerevisiae.
Conformations of Human Apolipoprotein E(263−286) and E(267−289) in Aqueous Solutions of Sodium Dodecyl Sulfate by CD and 1H NMR, (1996)

Structures of apoE(263-286) and apoE(267-289) have been determined in aqueous solution containing 90-fold molar excess of perdeuterated sodium dodecyl sulfate by CD and 1H NMR. Conformations were calculated by distance geometry based on 370 and 276 NOE distance restraints, respectively. RMSD for superimposing the region 265-284 from an ensemble of 41 structures for apoE(263-286) is 0.64 +/- 0.17 A for backbone atoms (N, C alpha, C = O) and 1.51 +/- 0.13 A for all atoms. The backbone RMSD for an ensemble of 37 structures for apoE(267-289) is 0.74 +/- 0.21 A for the region 268-275 and 0.34 +/- 0.10 A for the region 276-286. A two-domain structure was found for apoE(267-289) with the C-terminal half adopting a very well defined helix and the N-terminal segment 268-275 a less well defined helix, suggesting that the N-terminus may weakly bind to SDS. For apoE(263-286), an amphipathic helix-bend-helix structural motif was found with all hydrophobic side chains on the concave face. The existence of a bend around residues Q273 to G278 is consistent with their temperature coefficients of amide protons as well as secondary shifts of alpha-protons. Comparison of the structures of the two peptides revealed that the enhanced binding of apoE(263-286) to lipid could be attributed to the formation of a hydrophobic cluster consisting of residues W264, F265, L268, and V269. Aromatic side chains are proposed to be especially important in anchoring apolipoprotein fragments to micelles.
Design of prodrugs (1985)

CONTENTS: 1. Design of prodrugs: Bioreversible derivatives for various functional groups and chemical entities (by H. Bundgaard). 2. Design of prodrugs based on enzyme-substrate specificity (by P.K. Banerjee and G.L. Amidon) 3. Pharmacokinetic aspects of prodrug design and evaluation (by R.E. Notari). 4. Sustained drug action accomplished by the prodrug approach (by A.A. Sinkula). 5. Site-specific drug delivery via prodrugs (by V.J. Stella and K.J. Himmelstein). 6. Decreased toxicity and adverse reactions via prodrugs (by G. Jones) 7. Prodrugs for improved formulation properties (by B.D. Anderson) 8. Prodrugs and skin absorption (by J. Hadgraft). 9. Prodrugs in cancer chemotherapy (by T.A. Conners) 10. Albumin: A natural carrier for drug and enzyme therapy (by M. J. Poznansky and D. Bhardwaj) 11. Prodrugs versus soft drugs (by N. Bodor).
Cytotoxic T-Cell Immunity to Influenza (1983)

In a study designed to determine whether cytotoxic T lymphocytes contribute to immunity against influenza virus infection, we inoculated 63 volunteers intranasally with live unattenuated influenza A/Munich/1/79 virus. Over the next seven days clinical observations were made, and the amount of virus shed was measured. The protective effects of preinfection serum antibody and of cytotoxic T-cell immunity against influenza A virus were assessed for each participant. All subjects with demonstrable T-cell responses cleared virus effectively. This response was observed in volunteers in all age groups, including those born after 1956, who did not have specific antibody and hence had probably not been exposed to this subtype of influenza A virus before. Cytotoxic T cells show cross-reactivity in their recognition of the different subtypes of influenza A virus, in contrast to the antibody response that is specific for each virus subtype. We conclude that cytotoxic T cells play a part in recovery from influenza virus infection.
FGF‐2/fibroblast growth factor receptor/heparin‐like glycosaminoglycan interactions: a compensation model for FGF‐2 signaling (1999)

Heparin-like glycosaminoglycans (HLGAGs) play a central role in the biological activity and signaling behavior of basic fibroblast growth factor (FGF-2). Recent studies, however, indicate that FGF-2 may be able to signal in the absence of HLGAG, raising the question of the nature of the role of HLGAG in FGF-2 signaling. In this study, we present a conceptual framework for FGF-2 signaling and derive a simple model from it that describes signaling via both HLGAG-independent and HLGAG-dependent pathways. The model is validated with F32 cell proliferation data using wild-type FGF-2, heparin binding mutants (K26A, K119A/R120A, K125A), and receptor binding mutants (Y103A, Y111A/W114A). In addition, this model can predict the cellular response of FGF-2 and its mutants as a function of FGF-2 and HLGAG concentration based on experimentally determined thermodynamic parameters. We show that FGF-2-mediated cellular response is a function of both FGF-2 and HLGAG concentrations and that a reduction of one of the components can be compensated for by an increase in the other to achieve the same measure of cellular response. Analysis of the mutant FGF-2 molecules show that reduction in heparin binding interactions and primary receptor site binding interactions can also be compensated for in the same manner. These results suggest a molecular mechanism that could be used by cells in physiological systems to modulate the FGF-2-mediated cellular response by controlling HLGAG expression.
Crystal Structure of a Conserved Ribosomal Protein-RNA Complex (1999)

The structure of a highly conserved complex between a 58-nucleotide domain of large subunit ribosomal RNA and the RNA-binding domain of ribosomal protein L11 has been solved at 2.8 angstrom resolution. It reveals a precisely folded RNA structure that is stabilized by extensive tertiary contacts and contains an unusually large core of stacked bases. A bulge loop base from one hairpin of the RNA is intercalated into the distorted major groove of another helix; the protein locks this tertiary interaction into place by binding to the intercalated base from the minor groove side. This direct interaction with a key ribosomal RNA tertiary interaction suggests that part of the role of L11 is to stabilize an unusual RNA fold within the ribosome.
Total Synthesis of Everninomicin 13,384-1-Part 4: Explorations of Methodology; Stereocontrolled Synthesis of 1,1′-Disaccharides, 1,2-Seleno Migrations in Carbohydrates, and Solution- and Solid-Phase Synthesis of 2-Deoxy Glycosides and Orthoesters (2000)

Methods for the stereocontrolled construction of 1,1'-disaccharides, 2-deoxy glycosides, and orthoesters are reported. Specifically, a tin-acetal moiety was utilized to fix the anomeric stereochemistry of a carbohydrate acceptor leading to an efficient and stereoselective synthesis of 1,1'-disaccharides, while a newly discovered 1,2-phenylseleno migration reaction in carbohydrates opened entries to 2-deoxy glycosides and orthoesters. Thus, reaction of 2-hydroxy phenylselenoglycosides with DAST led to 2-phenylselenoglycosyl fluorides which reacted with carbohydrate acceptors to afford, stereoselectively, 2-phenylselenoglycosides. The latter compounds could be reductively deselenated to 2-deoxy glycosides or oxidatively converted to orthoesters via the corresponding ketene acetals.