gebhart/patrepeval huggingface dataset:
Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial (2003)

Intention to treat group comparisons indicated that at the mean dose taken, enrichment with n-3 fatty acids did not provide a therapeutic advantage and that both supplements were equally effective in arresting weight loss. Post hoc dose-response analysis suggests that if taken in sufficient quantity, only the n-3 fatty acid enriched energy and protein dense supplement results in net gain of weight, lean tissue, and improved quality of life. Further trials are required to examine the potential role of n-3 enriched supplements in the treatment of cancer cachexia.
Network Theory Reveals Principles of Spliceosome Structure and Dynamics (2021)

Abstract Cryo-EM has revolutionized structural biology of the spliceosome and dozens of distinct spliceosome structures representing much of the splicing cycle have now been determined. However, comparison of these structures is challenging due to extreme compositional and conformational dynamics of the splicing machinery and the thousands of intermolecular interactions created or dismantled as splicing progresses. We have used network theory to quantitatively analyze the dynamic interactions of splicing factors throughout the splicing cycle by constructing structure-based networks from every protein-protein, protein-RNA, and RNA-RNA interaction found in eight different spliceosome structures. Our networks reveal that structural modules comprising the spliceosome are highly dynamic with factors oscillating between modules during each stage along with large changes in the algebraic connectivities of the networks. Overall, the spliceosome’s connectivity is focused on the active site in part due to contributions from non-globular proteins and components of the NTC. Many key components of the spliceosome including Prp8 and the U2 snRNA exhibit large shifts in both eigenvector and betweenness centralities during splicing. Other factors show transiently high betweenness centralities only at certain stages thereby suggesting mechanisms for regulating splicing by briefly bridging otherwise poorly connected network nodes. These observations provide insights into the organizing principles of spliceosome architecture and provide a framework for comparative network analysis of similarly complex and dynamic macromolecular machines.
Molecular Cloning and Characterization of a Novel p70 S6 Kinase, p70 S6 Kinase β Containing a Proline-rich Region (1998)

A novel ribosomal S6 kinase, termed p70 S6 kinase beta (p70beta), which has a highly conserved amino acid sequence compared with that of p70/p85 S6 kinase (p70alpha) within the catalytic, kinase extension, and autoinhibitory pseudosubstrate domains, was identified. However, the amino acid sequence of p70beta differs from that of p70alpha in the noncatalytic amino-terminal region and in the carboxyl-terminal tail, which contains a proline-rich region. The majority of the regulatory phosphorylation sites identified in p70alpha are conserved in p70beta. Two isoforms of p70beta, referred to as beta1 (495 amino acids) and beta2 (482 amino acids), could be expressed from the single gene either by alternative mRNA splicing or by the use of alternative start codons. Here we report the characterization of p70beta2. Similarly to p70alpha, the catalytic activity of p70beta toward ribosomal protein S6 could be rapidly activated by serum, insulin, and phorbol ester in transiently transfected cells. The p70beta kinase was found to be significantly less sensitive to wortmannin and rapamycin than p70alpha. These results indicate that p70beta has the potential to participate in the regulation of protein synthesis and the cell cycle.
Antileishmanial drug targeting through glycosylated polymers specifically internalized by macrophage membrane lectins (1992)

Antileishmanial chemotherapy is hampered by the location of the parasite within the phagolysosome of the macrophage, which restricts the bioavailability of many potentially useful antileishmanial drugs. In this study, the possibility of using antileishmanial drugs targeted to the infected macrophages by means of a chemical linkage to a neutral mannose-substituted poly-L-lysine carrier molecule was explored. The study was performed in an in vitro model with Leishmania donovani-infected murine macrophages. The antileishmanial activities of various synthetic constructs were compared with those of the free drugs and the pentavalent antimonial Pentostam, which was used as the positive control. The 50% effective dose of allopurinol riboside linked to the mannosylated poly-L-lysine was below 7.5 x 10(-6) M, while it was up to 3 x 10(-4) M for the free drug, indicating that the drug bound to the polymer was 50 times more active than the free drug. Control experiments with other constructs (e.g., allopurinol riboside linked to the mannose-free polymer) confirmed that the enhancement of activity was indeed achieved by means of the mannose homing device.
Audio-Visual Speech Recognition Using Lip Information Extracted from Side-Face Images (2007)

This paper proposes an audio-visual speech recognition method using lip information extracted from side-face images as an attempt to increase noise robustness in mobile environments. Our proposed method assumes that lip images can be captured using a small camera installed in a handset. Two different kinds of lip features, lip-contour geometric features and lip-motion velocity features, are used individually or jointly, in combination with audio features. Phoneme HMMs modeling the audio and visual features are built based on the multistream HMM technique. Experiments conducted using Japanese connected digit speech contaminated with white noise in various SNR conditions show effectiveness of the proposed method. Recognition accuracy is improved by using the visual information in all SNR conditions. These visual features were confirmed to be effective even when the audio HMM was adapted to noise by the MLLR method.
Intrarater and interrater reliability of the MS functional composite outcome measure (2000)

The MS functional composite (MSFC) outcome measure had excellent intrarater and interrater reliability when standardized procedures were used to train examining technicians and to assess patients. Prebaseline testing sessions should be included in clinical trials employing the MSFC to compensate for practice effects.
Analysis and Purification of Synthetic Oligonucleotides by High-Performance Liquid Chromatography (1994)

Synthetic oligonucleotides are important in a wide variety of applications ranging from use as hybridization probes (1), primers for DNA sequencing and the polymerase chain reaction (2,3), to utilization as potential therapeutics in antisense and related technology investigations (4). In brief, their synthesis is most frequently performed via a series of systematic reactions that result in the stepwise addition of specific nucleotides [(protected at their 5′ hydroxy end with a dimeth-oxytrityl group (DMT)] to the solid phase support containing the growing chain. Variation in choice of incoming nucleotide monomers as well as modifications during or after the standard phosphodiester synthesis protocol can result in a final product containing atypical base, sugar, and/or phosphate backbone structures. Examples of such modifications may include substitution of a sulfur for an oxygen atom on the phosphate backbone creating phosphorothioate DNA or substitution of a methyl or borane group in lieu of oxygen to create methyl-phosphonate or boranophosphonate DNA. These and other modifications from conventional phosphodiester DNA are currently being investigated in antisense-related therapeutic studies as ways to increase cellular uptake, biological activity, and survival in both in vitro and in vivo experiments (4). A more complete discussion concerning the synthesis of phosphodiester as well as modified oligonucleotide species are addressed in volume 20 of this series.
A frame-layer bit allocation for H.263+ (2000)

In typical block-based video coding, the rate-control scheme allocates a target number of bits to each frame of a video sequence and selects the block quantization parameters to meet the frame targets. In this work, we present a new technique for assigning such targets. This method has been adopted in the test model TMN10 of H.263+, but it is applicable to any video coder and is particularly useful for those that use B frames. Our approach selects the frame targets using formulas that result from combining an analytical rate-distortion optimization and a heuristic technique that compensates for the distortion dependency among frames. The method does not require pre-analyses, and encodes each frame only once; hence, it is geared toward low-complexity real-time video coding. We compare this new frame-layer bit allocation in TMN10 to that in MPEG-2's TM5 for a variety of bit rates and video sequences.
Structure and ligand specificity of the Drosophila melanogaster insulin receptor. (1987)

The insulin-binding and protein tyrosine kinase subunits of the Drosophila melanogaster insulin receptor homolog have been identified and characterized by using antipeptide antibodies elicited to the deduced amino acid sequence of the alpha and beta subunits of the human insulin receptor. In D. melanogaster embryos and cell lines, the insulin receptor contains insulin-binding alpha subunits of 110 or 120 kilodaltons (kDa), a 95-kDa beta subunit that is phosphorylated on tyrosine in response to insulin in intact cells and in vitro, and a 170-kDa protein that may be an incompletely processed receptor. All of the components are synthesized from a proreceptor, joined by disulfide bonds, and exposed on the cell surface. The beta subunit is recognized by an antipeptide antibody elicited to amino acids 1142 to 1162 of the human insulin proreceptor, and the alpha subunit is recognized by an antipeptide antibody elicited to amino acids 702 to 723 of the human proreceptor. Of the polypeptide ligands tested, only insulin reacts with the D. melanogaster receptor. Insulinlike growth factors type I and II, epidermal growth factor, and the silkworm insulinlike prothoracicotropic hormone are unable to stimulate autophosphorylation. Thus despite the evolutionary divergence of vertebrates and invertebrates, the essential features of the structure and intrinsic functions of the insulin receptor have been remarkably conserved.
Alpha-rhythm stimulation using brain entrainment enhances heart rate variability in subjects with reduced HRV (2013)

In the present research, we have used the brain entrainment (BWE) treatment simultaneously recording time series data of R-R intervals of the ECG during rest condition. In detail, we have used alpha brain stimulation and we have found that it induces an enhancement of HRV, particularly in Total Variability and Vagal Modulation activities. The experiment has been performed by us on ten subjects with age ranging from 20 to 70 years old. The risk induced from low HRV is by this time well known in literature. Therefore, the obtained result promises to be of valuable interest not only in terms of the basic neurological investigation but also because it delineates new possibilities in terms of clinical application.
Proximity ligation assays: a recent addition to the proteomics toolbox (2010)

An essential skill for every researcher is to learn how to select and apply the most appropriate methods for the questions they are trying to answer. With the extensive variety of methods available, it is increasingly important to scrutinize the advantages and disadvantages of these techniques prior to making a decision on which to use. In this article, we describe an approach to evaluate methods by reducing them into subcomponents. This is exemplified by a brief description of some commonly used proteomics methods. The same approach can also be used in method development by rearranging subcomponents in order to create new methods, as demonstrated with the development of proximity ligation assays (PLAs). PLA is a method as designed in our laboratory for detection of proteins, protein-protein interactions and post-translational modifications. Fundamentally, protein-recognition events are converted into detectable DNA molecules. The technique uses protein-DNA conjugates as binders for the targets of interest. Binding of two or more conjugates to the target results in assembly of an assay-specific DNA molecule. Subsequent amplification of the DNA molecule generates a signal that can be detected using PCR, for detection of minute amounts of proteins in serum, or standard fluorescence microscopy for detection of protein-protein interactions in tissue sections. Lastly, we apply the approach of recombining subcomponents to develop a few novel hypothetical methods hoping this might stimulate the readers to utilize this approach themselves.
Biobutanol: An attractive biofuel (2007)

Biofuels are an attractive means to prevent a further increase of carbon dioxide emissions. Currently, gasoline is blended with ethanol at various percentages. However, butanol has several advantages over ethanol, such as higher energy content, lower water absorption, better blending ability, and use in conventional combustion engines without modification. Like ethanol, it can be produced fermentatively or petrochemically. Current crude oil prices render the biotechnological process economic again. The best-studied bacterium to perform a butanol fermentation is Clostridium acetobutylicum. Its genome has been sequenced, and the regulation of solvent formation is under intensive investigation. This opens the possibility to engineer recombinant strains with superior biobutanol-producing ability.
Spontaneous elaboration of transforming growth factor beta suppresses host defense against bacterial infection in autoimmune MRL/lpr mice. (1994)

Infection with gram-negative and gram-positive bacteria remains a leading cause of death in patients with systemic lupus erythematosis (SLE), even in the absence of immunosuppressive therapy. To elucidate the mechanisms that underly the increased risk of infection observed in patients with systemic autoimmunity, we have investigated host defense against bacterial infection in a murine model of autoimmunity, the MRL/Mp-lpr/lpr (MRL/lpr) mouse. Our previous study implicated transforming growth factor beta (TGF-beta) in a novel acquired defect in neutrophil function in MRL/lpr but not congenic MRL/Mp-+/+ (MRL/n) mice (Gresham, H.D., C.J. Ray, and F.K. O'Sullivan. 1991. J. Immunol. 146:3911). We hypothesized from these observations that MRL/lpr mice would have defects in host defense against bacterial infection and that they would have constitutively higher local and systemic levels of active TGF-beta which would be responsible, at least in part, for the defect in host defense. We show in this paper that spontaneous elaboration of active TGF-beta adversely affects host defense against both gram-negative and gram-positive bacterial infection in MRL/lpr mice. Our data indicate that MRL/lpr mice, as compared with congenic MRL/n mice, exhibit decreased survival in response to bacterial infection, that polymorphonuclear leukocytes (PMN) from MRl/lpr mice fail to migrate to the site of infection during the initial stages of infection, that MRL/lpr mice have a significantly increased bacterial burden at the site of infection and at other tissue sites, and that this increased bacterial growth occurs at a time (> 20 h after infection) when PMN influx is greatly enhanced in MRL/lpr mice. Most intriguingly, the alteration in PMN extravasation during the initial stages of infection and failure to restrict bacterial growth in vivo could be duplicated in MRL/n mice with a parenteral injection of active TGF-beta 1 at the time of bacterial challenge. Moreover, these alterations in host defense, including survival in response to lethal infection, could be ameliorated in MRL/lpr mice by the parenteral administration of a monoclonal antibody that neutralizes the activity of TGF-beta. These data indicate that elaboration of TGF-beta as a result of autoimmune phenomenon suppresses host defense against bacterial infection and that such a mechanism could be responsible for the increased risk of bacterial infection observed in patients with autoimmune diseases.
E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling (2015)

Inhibition of Poly(ADP-ribose) Polymerase1 (PARP1) impairs DNA damage repair, and early generation PARP1/2 inhibitors (olaparib, niraparib, etc.) have demonstrated clinical proof of concept for cancer treatment. Here, we describe the development of the novel PARP inhibitor E7449, a potent PARP1/2 inhibitor that also inhibits PARP5a/5b, otherwise known as tankyrase1 and 2 (TNKS1 and 2), important regulators of canonical Wnt/β-catenin signaling. E7449 inhibits PARP enzymatic activity and additionally traps PARP1 onto damaged DNA; a mechanism previously shown to augment cytotoxicity. Cells deficient in DNA repair pathways beyond homologous recombination were sensitive to E7449 treatment. Chemotherapy was potentiated by E7449 and single agent had significant antitumor activity in BRCA-deficient xenografts. Additionally, E7449 inhibited Wnt/β-catenin signaling in colon cancer cell lines, likely through TNKS inhibition. Consistent with this possibility, E7449 stabilized axin and TNKS proteins resulting in β-catenin de-stabilization and significantly altered expression of Wnt target genes. Notably, hair growth mediated by Wnt signaling was inhibited by E7449. A pharmacodynamic effect of E7449 on Wnt target genes was observed in tumors, although E7449 lacked single agent antitumor activity in vivo, a finding typical for selective TNKS inhibitors. E7449 antitumor activity was increased through combination with MEK inhibition. Particularly noteworthy was the lack of toxicity, most significantly the lack of intestinal toxicity reported for other TNKS inhibitors. E7449 represents a novel dual PARP1/2 and TNKS1/2 inhibitor which has the advantage of targeting Wnt/β-catenin signaling addicted tumors. E7449 is currently in early clinical development.
A Highly Linear and Efficient Differential CMOS Power Amplifier With Harmonic Control (2006)

A 2.45 GHz fully differential CMOS power amplifier (PA) with high efficiency and linearity is presented. For this work, a 0.18-/spl mu/m standard CMOS process with Cu-metal is employed and all components of the two-stage circuit except an output transformer and a few bond wires are integrated into one chip. To improve the linearity, an optimum gate bias is applied for the cancellation of the nonlinear harmonic generated by g/sub m3/ and a new harmonic termination technique at the common source node is adopted along with normal harmonic termination at the drain. The harmonic termination at the source effectively suppresses the second harmonic generated from the input and output. The amplifier delivers a 20.5dBm of P/sub 1dB/ with 17.5 dB of power gain and 37% of power-added efficiency (PAE). Linearity measurements from a two-tone test show that the power amplifier with the second harmonic termination improves the IMD3 and IMD5 over the amplifier without the harmonic termination by maximally 6 dB and 7 dB, respectively. Furthermore, the linearity improvements appear over a wide range of the power levels and the linearity is maintained under -45 dBc of IMD3 and -57dBc of IMD5 when the output power is backed off by more than 5dB from P/sub 1dB/. From the OFDM signal test, the second harmonic termination improves the error vector magnitude (EVM) by over 40% for an output power level satisfying the 4.6% EVM specification.
High-risk Human Papillomavirus E7 Oncoprotein Detection in Cervical Squamous Cell Carcinoma (2007)

This is the first study which systematically analyzes the levels of the major HPV oncoproteins in cervical carcinomas demonstrating that the high-risk HPV E7 proteins are regularly expressed in these cancers. This suggests that high-risk E7 oncoproteins are necessary for cervical cancers and apparently essential as tumor marker.
Distribution of Tumor-Infiltrating Immune Cells in Glioblastoma (2018)

Macrophages are more frequent than TILs. Some subsets are associated with clinical features.
Proteases Universally Recognize Beta Strands In Their Active Sites (2005)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProteases Universally Recognize Beta Strands In Their Active SitesJoel D. A. Tyndall, Tessa Nall, and David P. FairlieView Author Information Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia Cite this: Chem. Rev. 2005, 105, 3, 973–1000Publication Date (Web):February 16, 2005Publication History Received30 July 2004Published online16 February 2005Published inissue 1 March 2005https://doi.org/10.1021/cr040669eCopyright © 2005 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views3296Altmetric-Citations308LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (1 MB) Get e-AlertsSUBJECTS:Chemical structure,Conformation,Inhibitors,Monomers,Peptides and proteins Get e-Alerts
Admission Rapid Thrombelastography Can Replace Conventional Coagulation Tests in the Emergency Department (2012)

The r-TEG data was clinically superior to results from 5 CCTs. In addition, r-TEG identified patients with an increased risk of early RBC, plasma and platelet transfusions, and fibrinolysis. Admission CCTs can be replaced with r-TEG.
Computer Intrusion: Detecting Masquerades (2001)

Masqueraders in computer intrusion detection are people who use somebody else’s computer account. We investigate a number of statistical approaches for detecting masqueraders. To evaluate them, we collected UNIX command data from 50 users and then contaminated the data with masqueraders. The experiment was blinded. We show results from six methods, including two approaches from the computer science community.
Bionanoconjugation via Click Chemistry:  The Creation of Functional Hybrids of Lipases and Gold Nanoparticles (2006)

A simple and versatile method for the preparation of functional enzyme-gold nanoparticle conjugates using "click" chemistry has been developed. In a copper-catalyzed 1,2,3-triazole cycloaddition, an acetylene-functionalized Thermomyces lanuginosus lipase has been attached to azide-functionalized water-soluble gold nanoparticles under retention of enzymatic activity. The products have been characterized by gel electrophoresis and a fluorometric lipase activity assay. It is estimated that the equivalent of approximately seven fully active lipase molecules are attached to each nanoparticle.