gebhart/patrepeval huggingface dataset:
The genome of Syntrophus aciditrophicus : Life at the thermodynamic limit of microbial growth (2007)

Biochemically, the syntrophic bacteria constitute the missing link in our understanding of anaerobic flow of carbon in the biosphere. The completed genome sequence of Syntrophus aciditrophicus SB, a model fatty acid- and aromatic acid-degrading syntrophic bacterium, provides a glimpse of the composition and architecture of the electron transfer and energy-transducing systems needed to exist on marginal energy economies of a syntrophic lifestyle. The genome contains 3,179,300 base pairs and 3,169 genes where 1,618 genes were assigned putative functions. Metabolic reconstruction of the gene inventory revealed that most biosynthetic pathways of a typical Gram-negative microbe were present. A distinctive feature of syntrophic metabolism is the need for reverse electron transport; the presence of a unique Rnf-type ion-translocating electron transfer complex, menaquinone, and membrane-bound Fe-S proteins with associated heterodisulfide reductase domains suggests mechanisms to accomplish this task. Previously undescribed approaches to degrade fatty and aromatic acids, including multiple AMP-forming CoA ligases and acyl-CoA synthetases seem to be present as ways to form and dissipate ion gradients by using a sodium-based energy strategy. Thus, S. aciditrophicus, although nutritionally self-sufficient, seems to be a syntrophic specialist with limited fermentative and respiratory metabolism. Genomic analysis confirms the S. aciditrophicus metabolic and regulatory commitment to a nonconventional mode of life compared with our prevailing understanding of microbiology.
Reversible disulphide formation in polymer networks: A versatile functional group from synthesis to applications (2013)

A substantial effort has been made in the last few decades to develop responsive materials that produce a selective answer to well-defined environmental stimuli. In our present review, we focus on the chemistry of thiol–disulphide equilibrium and its incorporation into polymer-based soft materials. Because several papers and extensive reviews have focused on reduction-sensitive drug delivery and gene transfer, we would like to especially emphasise the importance of disulphide formation and the exploitation of reversible thiol–disulphide interconversion in synthesis and its applications. We report the most important synthetic strategies that utilise disulphide formation. However, a major portion of our overview will concentrate on taking advantage of the thiol–disulphide exchange and the reversibility of this reaction in a wide range of applications, such as advanced drug delivery vehicles, bioartificial implants and self-healing and shape-imprinting polymers. In certain cases, the reversibility is only proven and used in one cycle, but in some cases, the process is practically reversible, at least in the time range of the dedicated application. The reversibility of the reaction is an important requirement for the long-term use of these polymers as implant materials; therefore, aside from better understanding the redox processes in living cells, the future direction of this research can lead to the improvement of reversible responses.
Porochemoelastic Solution for an Inclined Borehole in a Transversely Isotropic Formation (2006)

A porochemoelastic model which couples the chemical interactions effected by solute and ionic transport with the diffusion-deformation processes is presented. The chemical effects are encompassed within the model assuming the saturating pore fluid to be a two species constituent comprising of the solute and the solvent. Governing equations are presented in their anisotropic forms and specialized for the transversely isotropic material. The resulting system of equations is applied to obtain the porochemoelastic analytical solution for an inclined borehole subjected to a three-dimensional state of stress in a transversely isotropic formation. In obtaining the analytical solutions, it is assumed that the borehole axis is perpendicular to the plane of isotropy of the transversely isotropic formation. Chemical effects on the stress and pore pressure distributions and their impact on borehole stability is demonstrated in the numerical examples included.
Validation of a modified Early Warning Score in medical admissions (2001)

The Early Warning Score (EWS) is a simple physiological scoring system suitable for bedside application. The ability of a modified Early Warning Score (MEWS) to identify medical patients at risk of catastrophic deterioration in a busy clinical area was investigated. In a prospective cohort study, we applied MEWS to patients admitted to the 56-bed acute Medical Admissions Unit (MAU) of a District General Hospital (DGH). Data on 709 medical emergency admissions were collected during March 2000. Main outcome measures were death, intensive care unit (ICU) admission, high dependency unit (HDU) admission, cardiac arrest, survival and hospital discharge at 60 days. Scores of 5 or more were associated with increased risk of death (OR 5.4, 95%CI 2.8-10.7), ICU admission (OR 10.9, 95%CI 2.2-55.6) and HDU admission (OR 3.3, 95%CI 1.2-9.2). MEWS can be applied easily in a DGH medical admission unit, and identifies patients at risk of deterioration who require increased levels of care in the HDU or ICU. A clinical pathway could be created, using nurse practitioners and/or critical care physicians, to respond to high scores and intervene with appropriate changes in clinical management.
The era of anti-vascular endothelial growth factor (VEGF) drugs in ophthalmology, VEGF and anti-VEGF therapy (2016)

Angiogenesis is a clue process for tissue development and function, both in normal and pathological conditions. This process is regulated by multiple molecular systems. One of the most potent is vascular endothelial growth factor (VEGF) and its receptor (VEGFR) system. Members of this family are involved in new vessel formation in embryogenesis and maturation, as well as in reparative or pathological reactions in later stages. They play a substantial role in regeneration, inflammation, wound healing, as well as in cancer pathology. Nowadays it is possible to modulate VEGF-VEGFR interactions in many pathological conditions using anti-VEGF therapy. This therapy has already achieved a grounded position in the management of rheumatological disorders, tumour progression, and metastasis. Such drugs as bevacizumab, ranibizumab, aflibercept, and pegaptanib have also proven to be very effective in the treatment of several ocular diseases, such as age-related macular degeneration (AMD), macular oedema, or proliferative retinopathies and iris neovascularisation. The indications for the application of this therapy in ophthalmology are becoming wider and wider. It may also be used for corneal pathologies and in anti-glaucoma procedures.
Neutrophil elastase inhibitors for the treatment of (cardio)pulmonary diseases: Into clinical testing with pre-adaptive pharmacophores (2015)

Alpha-1 antitrypsin deficiency is linked with an increased risk of suffering from lung emphysema. This discovery from the 1960s led to the development of the protease-antiprotease (im)balance hypothesis: Overshooting protease concentrations, especially high levels of elastase were deemed to have an destructive effect on lung tissue. Consequently, it was postulated that efficient elastase inhibitors could alleviate the situation in patients. However, despite intensive drug discovery efforts, even five decades later, no neutrophil elastase inhibitors are available for a disease-modifying treatment of (cardio)pulmonary diseases such as chronic obstructive pulmonary disease. Here, we critically review the attempts to develop effective human neutrophil elastase inhibitors while strongly focussing on recent developments. On purpose and with perspective distortion we focus on recent developments. One aim of this review is to classify the known HNE inhibitors into several generations, according to their binding modes. In general, there seem to be three major challenges in the development of suitable elastase inhibitors: (1) assuring sufficient potency, (2) securing selectivity, and (3) achieving metabolic stability especially under pathophysiological conditions. Impressive achievements have been made since 2001 with the identification of potent nonreactive, reversible small molecule inhibitors. The most modern inhibitors bind HNE via an induced fit with a frozen bioactive conformation that leads to a significant boost in potency, selectivity, and stability ('pre-adaptive pharmacophores'). These 5th generation inhibitors might succeed in re-establishing the protease-antiprotease balance in patients for the first time.
Clinical Experience with Fibrin Glue in Cardiac Surgery (1981)

Cardiac surgery is often associated with hemostatic abnormalities leading to severe bleeding. Special problems are to be expected, if prosthetic material has to be implanted. Preclotting of Dacron prostheses with blood is well established but failures are sometimes encountered. Several years ago a new hemostatic sealing system (fibrin glue) was introduced into therapy. Since 1978 fibrin glue has been applied in 176 patients. The indications were: 1. sealing of woven Dacron prostheses, 2. bleeding from suture-holes (Gore-Tex), 3. diffuse myocardial bleeding and 4. prevention of kinking of coronary artery grafts. In 32 patients with an aortoventriculoplasty operation using Dacron the "blood preclotting" and "fibrin sealing" methods were compared. In the fibrin glue group there was a significant reduction in postoperative blood loss as well as a shortening of the operation time (period of protamin administration to skin closure). No fibrinolytic dissolution of the fibrin layer on the prostheses was observed.
Functional association of the N‐terminal residues with the central region in glucagon‐related peptides (2011)

GLP-1 is an incretin peptide involved in the regulation of glucose metabolism and the glucose-dependent stimulation of insulin secretion. Ex-4 is a paralog of GLP-1 that has comparable GLP-1R potency but extended physiological action. GLP-1 and Ex-4 are helical peptides that share ∼50% sequence homology but differ at several residues, notably the second amino acid which controls susceptibility to DPP-IV cleavage. This single amino acid difference yields divergent receptor potency when studied in the context of the two hormone sequences. Ex-4 uniquely tolerates Gly2 through select amino acid differences in the middle region of the peptide that are absent in GLP-1. We report that substitution of Ex-4 amino acids Glu16, Leu21, and Glu24 to the GLP-1 sequence enabled Gly2 tolerance. The coordination of the N-terminus with these central residues shows an interaction of substantial importance not only to DPP-IV stability but also to receptor activation. Extension of this observation to glucagon-based co-agonist peptides showed different structural requirements for effective communication between the N-terminus and the mid-section of these peptides in achieving high potency agonism at the GLP-1 and GCGRs.
Superhydrophobic surfaces: from structural control to functional application (2007)

A superhydrophobic surface is a surface with a water contact angle close to or higher than 150°. In this feature article, we review the historical and present research on superhydrophobic surfaces, including the characterization of superhydrophobicity, different ways to fabricate rough surfaces, and low-surface-energy modifications on inorganic and organic rough surfaces. It is the combination of surface roughness and low-surface-energy modification that leads to superhydrophobicity. Notably, research on superhydrophobic surfaces has not only fundamental interest but various possible functional applications in micro- and nano-materials and devices.
Clinical trials using polyadenylic-polyuridylic acid as an adjuvant to surgery in treating different human tumors. (1985)

The results of a randomized trial of polyadenylic-polyuridylic [poly(A).poly(U)] acid given as adjuvant treatment for operable breast cancer were reviewed after a mean follow-up period of 87 months. The overall survival was significantly improved in patients given the adjuvant (155 cases) as compared with the controls (145 cases). A significant benefit was observed in patients with invaded axillary nodes; the best results were obtained in the group of patients with up to three nodes involved, who showed a significant increase in both overall and relapse-free survival. The biological response modifications observed after treatment with poly(A).poly(U), namely, production of interferon and increase of natural killer cell activity, are described and their possible role in the mechanism of action of the complex is discussed. The results of a Phase I clinical tolerance study of the duplex in cancer patients will be reported. The aims and protocols of new clinical trials with adjuvant poly(A).poly(U) in different types of tumors will be presented.
Optical sensors. Part 34. Fibre optic glucose biosensor with an oxygen optrode as the transducer (1988)

A biosensor for the continuous determination of glucose is presented. Glucose oxidase was immobilised covalently on a nylon membrane and the consumption of oxygen was measured by following, via fibre optic bundles, the changes in the fluorescence of an oxygen-sensitive dye whose fluorescence is quenched dynamically by molecular oxygen. The dye is dissolved in a very thin silicone membrane placed beneath the enzyme layer. As a result of the oxidation by the enzyme a certain amount of oxygen is consumed. This amount is indicated by the fluorescent dye. The measurements were performed in flowing air-saturated solutions containing 0.1 M pH 7.0 phosphate buffer. The effects of the amount of immobilised enzyme and the thickness of the indicator layer on response times (t90= 1–6 min), analytical ranges (0.1–20 mM) and relative signal changes (up to 26%) were investigated.
Signal-processing techniques for cochlear implants (1999)

Cochlear implants have been successful in restoring partial hearing to profoundly deaf people. The success of cochlear implants can be attributed to the combined efforts of scientists from various disciplines, including bioengineering, physiology, otolaryngology, speech science, and signal processing. Each of these disciplines contributed to various aspects of the cochlear implant design. Signal processing, in particular, played an important role in the development of different techniques for deriving electrical stimuli from the speech signal. The purpose of this article is to present a review of various signal-processing techniques that have been used for cochlear prosthesis over the past 25 years.
Coronary heart disease risk factors ranked by importance for the individual and community. A 21 year follow-up of 12000 men and women from The Copenhagen City Heart Study (2002)

The importance of coronary heart disease risk factors may differ for individuals, the community, and by sex and age. Consequently, prevention strategies should be tailored accordingly.
Optimization of Lipid Nanoparticle Formulations for mRNA Delivery in Vivo with Fractional Factorial and Definitive Screening Designs (2015)

Intracellular delivery of messenger RNA (mRNA) has the potential to induce protein production for many therapeutic applications. Although lipid nanoparticles have shown considerable promise for the delivery of small interfering RNAs (siRNA), their utility as agents for mRNA delivery has only recently been investigated. The most common siRNA formulations contain four components: an amine-containing lipid or lipid-like material, phospholipid, cholesterol, and lipid-anchored polyethylene glycol, the relative ratios of which can have profound effects on the formulation potency. Here, we develop a generalized strategy to optimize lipid nanoparticle formulations for mRNA delivery to the liver in vivo using Design of Experiment (DOE) methodologies including Definitive Screening and Fractional Factorial Designs. By simultaneously varying lipid ratios and structures, we developed an optimized formulation which increased the potency of erythropoietin-mRNA-loaded C12-200 lipid nanoparticles 7-fold relative to formulations previously used for siRNA delivery. Key features of this optimized formulation were the incorporation of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and increased ionizable lipid:mRNA weight ratios. Interestingly, the optimized lipid nanoparticle formulation did not improve siRNA delivery, indicating differences in optimized formulation parameter design spaces for siRNA and mRNA. We believe the general method described here can accelerate in vivo screening and optimization of nanoparticle formulations with large multidimensional design spaces.
Computing Mel-frequency cepstral coefficients on the power spectrum (2002)

We present a method to derive Mel-frequency cepstral coefficients directly from the power spectrum of a speech signal. We show that omitting the filterbank in signal analysis does not affect the word error rate. The presented approach simplifies the speech recognizers front end by merging subsequent signal analysis steps into a single one. It avoids possible interpolation and discretization problems and results in a compact implementation. We show that frequency warping schemes like vocal tract normalization can be integrated easily in our concept without additional computational efforts. Recognition test results obtained with the RWTH large vocabulary speech recognition system are presented for two different corpora: The German VerbMobil II dev99 corpus, and the English North American Business News 94 20k development corpus.
Immunogenicity of a chimeric peptide corresponding to T helper and B cell epitopes of the Chlamydia trachomatis major outer membrane protein. (1992)

The immunogenicity of a chimeric T/B cell peptide corresponding to antigenically characterized epitopes of the Chlamydia trachomatis major outer membrane protein (MOMP) was studied in mice to further define its potential use in the development of a subunit vaccine in preventing blinding trachoma in humans. The chimeric peptide, designated A8-VDI, corresponds to a conserved MOMP T helper (Th) cell epitope(s) (A8, residues 106-130) and serovar A VDI (residues 66-80), which contains the serovar-specific neutralizing epitope 71VAGLEK76. Mice immunized with peptide A8-VDI produced high-titered polyclonal IgG antibodies which recognized the VAGLEK-neutralizing epitope. Peptide A8-VDI primed A/J mice to produce high-titered serum-neutralizing antibodies in response to a secondary immunization with intact chlamydial elementary bodies (EBs). Peptide A8-VDI, but not peptide VDI alone, was immunogenic in six different inbred strains of mice disparate at H-2, indicating that the Th cell epitope(s) contained in the A8 portion of the chimera was recognized in the context of multiple major histocompatibility complex (MHC) haplotypes. An unexpected finding of this work was that different inbred strains of mice immunized with the chimeric peptide produced antibodies of differing fine specificities to the VDI portion of the chimera. Some mouse strains produced anti-VDI antibodies that did not recognize the VAGLEK-neutralizing epitope. The ability of mice to respond to the VAGLEK-neutralizing site was not dependent on MHC haplotype since mouse strains of the same H-2 haplotype produced anti-VDI antibodies of differing fine specificity.
Study on maintenance operations in a chord-based Peer-to-Peer session initiation protocol overlay network (2009)

Peer-to-Peer Session Initiation Protocol (P2PSIP) is a new technology being standardized in the Internet Engineering Task Force. A P2PSIP network consists of a collection of nodes organized in a peer-to-peer fashion for the purpose of enabling real-time communication using the Session Initiation Protocol (SIP). In this paper, we present experimental results obtained by running a P2PSIP prototype in PlanetLab. Our prototype uses the Chord Distributed Hash Table (DHT) to organize the P2PSIP overlay and Peer-to-Peer Protocol (P2PP) as the protocol spoken between the peers. In the experiments, the performance of the system is studied under different churn rates and using different DHT maintenance intervals.
Glutathione peroxidase‐like activity of caeruloplasmin as an important lung antioxidant (1999)

The copper‐containing plasma protein caeruloplasmin (Cp) has been shown to possess several oxidase activities, but with the exception of its ferrous ion oxidising (ferroxidase) activity which so far appear to be of minor biological relevance. Recently, Kim and colleagues (Kim et al. (1998) FEBS Lett. 431, pp. 473–475) observed that Cp can catalytically remove hydrogen peroxide in the presence of thiols. Here, we show that Cp can remove both hydrogen peroxide and lipid hydroperoxides at physiologically relevant concentrations of reduced glutathione known to be present in lung and lung lining fluid. The glutathione peroxidase‐like activity of Cp together with its ferroxidase activity would completely remove the primary reactants required for both Fenton chemistry and lipid peroxidation.
Inhibition of Ran Guanosine Triphosphatase-Dependent Nuclear Transport by the Matrix Protein of Vesicular Stomatitis Virus (1997)

Transport of macromolecules into and out of nuclei, essential steps in gene expression, are potential points of control. The matrix protein (M protein) of vesicular stomatitis virus (VSV) was shown to block transport of RNAs and proteins between the nucleus and cytoplasm of Xenopus laevis oocytes. The pattern of inhibition indicated that M protein interfered with transport that is dependent on the ras-like nuclear guanosine triphosphatase (GTPase) Ran-TC4 and its associated factors. This inhibition of nuclear transport by M protein explains several observations about the effects of VSV infection on host cell gene expression and suggests that RNA export is closely coupled to protein import.
Molecular Mechanism for the Shp-2 Tyrosine Phosphatase Function in Promoting Growth Factor Stimulation of Erk Activity (2000)

We have previously shown that activation of extracellular signal-regulated kinase (Erk) by epidermal growth factor (EGF) treatment was significantly decreased in mouse fibroblast cells expressing a mutant Shp-2 molecule lacking 65 amino acids in the SH2-N domain, Shp-2(Delta46-110). To address the molecular mechanism for the positive role of Shp-2 in mediating Erk induction, we evaluated the activation of signaling components upstream of Erk in Shp-2 mutant cells. EGF-stimulated Ras, Raf, and Mek activation was significantly attenuated in Shp-2 mutant cells, suggesting that Shp-2 acts to promote Ras activation or to suppress the down-regulation of activated Ras. Biochemical analyses indicate that upon EGF stimulation, Shp-2 is recruited into a multiprotein complex assembled on the Gab1 docking molecule and that Shp-2 seems to exert its biological function by specifically dephosphorylating an unidentified molecule of 90 kDa in the complex. The mutant Shp-2(Delta46-110) molecule failed to participate in the Gab1-organized complex for dephosphorylation of p90, correlating with a defective activation of the Ras-Raf-Mek-Erk cascade in EGF-treated Shp-2 mutant cells. Evidence is also presented that Shp-2 does not appear to modulate the signal relay from EGF receptor to Ras through the Shc, Grb2, and Sos proteins. These results begin to elucidate the mechanism of Shp-2 function downstream of a receptor tyrosine kinase to promote the activation of the Ras-Erk pathway, with potential therapeutic applications in cancer treatment.