gebhart/patrepeval huggingface dataset:
Detection of a key tertiary interaction in the highly conserved GTPase center of large subunit ribosomal RNA. (1991)

Searches of ribosomal RNA sequences for compensatory base changes preserving Watson-Crick base pairing have led to detailed models of the conserved secondary structures of these RNAs. In principle, tertiary interactions can also be detected by searches for phylogenetically covariant bases. Within a highly conserved region of the large subunit ribosomal RNA termed the "GTPase center," the bases G-1056-U-1082.A-1086 are found in all eubacteria (Escherichia coli numbering), while A-1056.C-1082.G-1086 are found at the homologous positions in eukaryotes; archaebacteria fall into either category with some exceptions. Either sequence can potentially form a similar set of hydrogen bonds connecting the 3 bases. To determine the contribution of these 3 bases to RNA tertiary structure, sequence variants were made in RNA fragments covering the GTPase center. Correct folding of the RNA fragments was assayed by measuring the binding affinities of two different ligands that recognize the RNA tertiary structure: the highly conserved ribosomal protein L11, which is normally associated with the GTPase center RNA, and the peptide antibiotic thiostrepton, which inhibits the GTPase activity of eubacterial and some archaebacterial ribosomes. The results strongly support the existence of a base pair between positions 1082 and 1086: single mutations at either position weaken both L11 and thiostrepton binding by approximately 10-fold or more, while compensatory double mutations bind the ligands nearly as well as the wild-type E. coli sequence. Variants at position 1056 have little effect on either L11 or thiostrepton binding; a 3-base interaction is therefore not supported by these experiments. A base pair between positions 1082 and 1086 strongly constrains the geometry with which three helical segments join in the middle of the GTPase center.
Effect of Cell Morphology on the Properties of Microcellular Foamed PVC/Wood-Fiber Composites (1996)

Abstract Wood-fiber composites make use of cellulose fibers as a reinforcing filler in the polymer matrix and are known to have a lower material cost and a higher stiffness compared to neat polymers. However, the lower material cost and enhanced stiffness of wood-fiber composites are achieved at the expense of other properties such as the ductility and the impact strength. Since microcellular plastics exhibit a higher relative impact strength, higher relative toughness, and increased relative fatigue life compared to unfoamed plastics, microcellular foaming of wood-fiber composites will improve the mechanical properties of the composites and therefore increase the usefulness of the materials. In this paper, microcellular foamed PVC/wood-fiber composites with unique cell morphology and material composition are characterized. Microcellular structures are produced in PVC/wood-fiber composites by first saturating the composite samples with CO2 under high pressure followed by rapidly decreasing the solubility of gas in the samples. The void fraction of the microcellular foamed PVC/wood-fiber composites is controlled by tailoring the composition of materials and the foaming process parameters. The results indicate that tensile and impact properties of microcellular foamed PVC/wood-fiber composites are most sensitive to changes in the cell morphology and the surface modification of fibers.
Gene therapy in diabetes mellitus: promises and piffalls. (1999)

After some initial disappointments, the field of gene therapy is now gaining confidence and momentum. Recent improvements in gene transfer techniques promise targeted and supra-threshold levels of transgene expression leading to the desired therapeutic effects. This increase in optimism has spread to thefield of diabetes research. Firstly, the recent developments in gene transfer techniques are now being tested on the pancreatic insulin producing beta-cell. For many gene therapy strategies in the treatment of diabetes, transfection of insulin producing cells is a prerequisite. Secondly, if efficient and safe vectors that transduce beta-cells in vivo or ex vivo are made available, autoimmune beta-cell destruction in type 1 diabetes could be prevented. In this strategy, it is envisaged that gene therapy will protect the remaining beta-cell mass in newly diagnosed diabetics or pre-diabetic individuals at a high risk of becoming diabetic from autoimmune destruction. Thirdly, attempts are being made to genetically engineer cells to become artificial beta-cells. Such cells could conceivably compensate for the lost endogeneous alpha-cell mass and restore a regulated insulin secretion. This review will attempt to predict the future of gene therapy in the treatment of diabetes.
Prevention and medical management of Clostridium difficile infection (2010)

#### Summary points

The incidence of Clostridium difficile infection in the United Kingdom has increased since the late 1990s.1 High profile outbreaks in the United States, Canada, and northern Europe have been associated with a previously uncommon but highly virulent strain known as ribotype 027. A recent review in the BMJ examined the role of surgery in treating C difficile colitis.2 This review focuses on the prevention and medical management of C difficile infection. Because few randomised controlled trials (RCTs) exist on this subject, our recommendations are based mainly on non-RCT studies and clinical governance reports.

#### Sources and selection criteria

We searched PubMed and Google Scholar for articles published from 2006 to 2009 on the treatment and prevention of Clostridium difficile infection and screened the reference lists of retrieved publications. We also consulted the Cochrane Library and the recent best practice guidance from the Health Protection Agency . 1

C difficile can be cultured from the stool of 3% of healthy adults and as many as 35% of hospital inpatients.3 Lower rates of nosocomial colonisation are seen in some studies, and may be dependent on patient population, length of hospital stay, and local infection control procedures.w1 w2 Most colonised people remain asymptomatic. Clinical disease develops when the normal gut flora is disrupted, usually by antibiotic exposure, thereby creating conditions that favour C difficile proliferation within the colon. Although C difficile infections in England have …
The isolated sinoatrial node cell in primary culture from the newborn rat. (1984)

We prepared primary cell cultures of the sinus node region from newborn rat hearts. Sinoatrial node cells were easily distinguished from the other cardiac muscle cells and nonmuscle cells in culture by size, configuration, and rapid, attenuated spontaneous contractions (185.0 +/- 8/min, mean +/- SEM). The spontaneously contracting sinoatrial node cells were extremely sensitive to acetylcholine and norepinephrine, responding to concentrations at least 1000-fold less than other cardiac muscle cells. These same sinoatrial node cells in culture were fixed and precisely relocated by either subsequent scanning or transmission electron microscopy. The ultrastructural features of these sinoatrial node cells in culture were similar to those observed in the cells of intact sinus node sections from the source hearts. This study is the first to present single, spontaneously active, neonatal sinoatrial node cells maintained in vitro with morphological and functional properties desirable for physiological investigations.
Statistical characterization of gas-patch distributions in partially saturated rocks (2009)

Abstract Reservoir rocks are often saturated by two or more fluid phases forming complex patterns on all length scales. The objective of this work is to quantify the geometry of fluid phase distribution in partially saturated porous rocks using statistical methods and to model the associated acoustic signatures. Based on X-ray tomographic images at submillimeter resolution obtained during a gas-injection experiment, the spatial distribution of the gas phase in initially water-saturated limestone samples are constructed. Maps of the continuous variation of the percentage of gas saturation are computed and associated binary maps obtained through a global thresholding technique. The autocorrelation function is derived via the two-point probability function computed from the binary gas-distribution maps using Monte Carlo simulations. The autocorrelation function can be approximated well by a single Debye correlation function or a superposition of two such functions. The characteristic length scales and show sensitivity (and hence significance) with respect to the percentage of gas saturation. An almost linear decrease of the Debye correlation length occurs with increasing gas saturation. It is concluded that correlation function and correlation length provide useful statistical information to quantify fluid-saturation patterns and changes in these patterns at the mesoscale. These spatial statistical measures are linked to a model that predicts compressional wave attenuation and dispersion from local, wave-induced fluid flow in randomly heterogeneous poroelastic solids. In particular, for a limestone sample, with flow permeability of 5 darcies and an average gas saturation of ∼5%, significant P-wave attenuation is predicted at ultrasonic frequencies.
Lymphatic endothelium‐specific hyaluronan receptor LYVE‐1 is expressed by stabilin‐1<sup>+</sup>, F4/80<sup>+</sup>, CD11b<sup>+</sup> macrophages in malignant tumours and wound healing tissue <i>in vivo</i> and in bone marrow cultures <i>in vitro</i>: implications for the assessment of lymphangiogenesis (2006)

Lymphangiogenesis is a novel prognostic parameter for several cancers that is preferentially quantified by immunohistochemistry of the lymphatic endothelium-specific hyaluronan receptor LYVE-1. Recently, the specificity of LYVE-1 was challenged by serendipitous observations of LYVE-1 expression in rare tissue macrophages. As expression of the hyaluronan receptor-like molecule stabilin-1 is shared by sinusoidal endothelium and macrophages, a thorough analysis of LYVE-1 expression was performed using macrophage-specific markers in vivo and in vitro. In murine tumour models and excisional wound healing, LYVE-1 expression occurred in a subset of CD11b(+), F4/80(+) tissue macrophages that preferentially co-expressed stabilin-1. Upon comparison of single- and double-labelling immunofluorescence, it became apparent that LYVE-1(+) macrophages mimic sprouting and collapsed lymphatic vessels. In vitro, LYVE-1 expression was induced in 25-40% of murine bone marrow-derived macrophages upon exposure to B16F1 melanoma-conditioned medium and IL-4/dexamethasone. By FACS analysis, 11.5% of bone marrow-derived macrophages were LYVE-1(+), stabilin-1(+) double-positive, while 9.9% were LYVE-1(+), stabilin-1(-) and 33.5% were LYVE-1(-), stabilin-1(+). Northern and western analyses confirmed expression of LYVE-1 mRNA and protein in bone marrow-derived macrophages. In the light of the current debate about true endothelial trans-differentiation versus endothelial mimicry of monocytes/macrophages, LYVE-1(+), stabilin-1(+) non-continuous endothelial-like macrophages will require further developmental and functional analyses. In conclusion, the findings imply that LYVE-1 staining must be supplemented by double labelling with macrophage markers in order to differentiate clearly between LYVE-1(+) lymphatics and LYVE-1(+) tumour-infiltrating macrophages. This improved approach will help to clarify the prognostic significance of lymphangiogenesis in malignant tumours.
An Atypical Naturally Split Intein Engineered for Highly Efficient Protein Labeling (2014)

Protein trans-splicing catalyzed by split inteins is a powerful technique for assembling a polypeptide backbone from two separate parts. However, split inteins with robust efficiencies and short fragments suitable for peptide synthesis are rare and have mostly been artificially created. The novel split intein AceL-TerL was identified from metagenomic data and characterized. It represents the first naturally occurring, atypically split intein. The N-terminal fragment of only 25 amino acids is the shortest natural intein fragment to date and was easily amenable to chemical synthesis with a fluorescent label. Optimal protein trans-splicing activity was observed at low temperatures. Further improved mutants were selected by directed protein evolution. The engineered intein variants with up to 50-fold increased rates showed unprecedented efficiency in chemically labeling of a diverse set of proteins. These inteins should prove valuable tools for protein semi-synthesis and other intein-related biotechnological applications.
Growth dynamics of plexiform neurofibromas: a retrospective cohort study of 201 patients with neurofibromatosis 1 (2012)

Children with NF1 and internal PNs are at risk for tumour growth. Most PNs grow slowly or not at all, and some decrease in size. New tumours are infrequent in NF1 patients with PNs and unlikely in patients without PNs.
Effects of endothelin receptor antagonists on endothelin-1 and inducible nitric oxide synthase genes in a rat endotoxic shock model (2002)

Levels of the endothelium-derived vasoconstrictor endothelin (ET)-1 and the vasodilator nitric oxide (NO) are markedly increased in endotoxic shock, although the pathophysiological role of ET-1 and its relation to NO under septic conditions remains obscure. To delineate the roles of ET-1 and the ET receptors, and the NO/inducible NO synthase (iNOS) system in endotoxic shock, we examined the gene expression of ET-1, ET receptors A and B (ETA and ETB) and iNOS in the heart and the liver of a rat endotoxic shock model, and we studied the effects of ET receptor antagonists on haemodynamics, survival rate and expression of ET-1, ET receptors and iNOS. Administration of bacterial lipopolysaccharide (LPS) into rats caused a profound hypotension with resultant death. However, these effects were blocked by a non-selective ETA/ETB receptor antagonist (TAK044), but not by an ETA-selective antagonist (BQ123). Injection of LPS caused a marked elevation in the plasma levels of both ET-1 and NO, which were not affected by treatment with either ET receptor antagonist. Administration of LPS caused increases in levels of ET-1, ETB and iNOS mRNA in the heart and the liver, whereas ETA mRNA expression was markedly downregulated in these organs. These results suggest that ET receptor subtype genes are differentially regulated in major organs from endotoxic shock rats, and that non-selective ET receptor antagonists ameliorate endotoxin-induced hypotension and death irrespective of iNOS-derived NO.
Characterization of Diverse Viral Vector Preparations, Using a Simple and Rapid Whole-Virion Dot-Blot Method (1998)

A number of different viruses have been adapted as gene transfer vectors, including retroviruses, adenoviruses, adenoassociated viruses (AAVs), herpes simplex virus, SV40 viruses, and alphaviruses (both Semliki Forest and Sindbis viruses). One of the major rate-limiting and time-consuming steps in the characterization of these vectors is the process of determining the viral vector titers. In addition, there is no "universal" method that can be used to rapidly estimate the titer and the utility of viral vector preparations. We demonstrate here that supernatant from diverse classes of viral vectors, with either RNA or DNA genomes, can be rapidly evaluated by a simple virus dot-blot hybridization without prior extraction of nucleic acids. This system can provide a reliable screen for physical titer of viral vector supernatants in 1 day.
Absorption, transmission, and scattering of expanded polystyrene at millimeter-wave and terahertz frequencies (2008)

Conventional material measurements of transmission and reflection in the millimeter-wave and terahertz frequency range do not differentiate between scattering and absorption, grouping effects from both mechanisms together into "loss". Accurate knowledge of the balance between scattering and absorption is critical in applications such as radiometric scene modeling for concealed object detection, where evaluation of object detectability depends strongly on the amount of scattering due to concealers such as clothing. We describe an experimental setup for the measurement of spatial bidirectional reflectance distribution function (BRDF). Previous measurements have shown extremely low-level grating lobes from periodic clothing materials such as corduroy, around 30 dB below the transmitted beam. To adequately address this issue of high dynamic range, we utilize a cryogenic antenna-coupled microbolometer for detection. We present data on several types of expanded polystyrene, a common structural material for systems and experiments in this frequency range. In these measurements of BRDF, transmission agrees with previous measurements, and the balance between low and high angle scattering, specular reflectance, and absorption is examined.
Perceptual interactions in thermo-tactile displays (2017)

Thermo-tactile displays have been developed to enhance the degree of realism in virtual environments and assist in the identification of virtual objects. It is unknown whether the simultaneous presentation of thermal and tactile cues enhances user performance and if the two types of sensory signals can be processed independently or interact. The present experiment measured thermal pattern identification in the presence of concurrent vibrotactile feedback on the thenar eminence on the hand. The thermal patterns varied with respect to the direction, rate, and duration of the change in skin temperature and for the vibration inputs the number of pulses was varied. The results indicated that with concurrent tactile stimulation warm stimuli (89%) were easier to identify than cool stimuli (76%) and that the number of pulses in the vibration signal affected thermal identification. The mean Information Transfer (IT) associated with these thermo-tactile patterns was 1.94 bits. These thermal-tactile interactions indicate that in multi-sensory displays the ability to perceive independent channels of communication can be influenced by the concurrent presentation of other sensory cues.
Spatially interleaved architecture for high-frequency data converters (2016)

A Traveling-Wave ADC based on spatially interleaved sampling on a synthetic transmission line is proposed. Signal propagation on the transmission line generates the interleaving delay. This architecture enables extremely small sampling periods which allow for high sampling frequencies. Furthermore, the loaded T-line provides a broadband input impedance to enable extended input frequencies. The design tradeoffs are presented and the main challenges and opportunities in spatial interleaving are discussed. The relationship between transmission line parameters and the ADC specifications is investigated through a design example.
Pressure-Dependent Ion Current Rectification in Conical-Shaped Glass Nanopores (2011)

Ion current rectification that occurs in conical-shaped glass nanopores in low ionic strength solutions is shown to be dependent on the rate of pressure-driven electrolyte flow through the nanopore, decreasing with increasing flow rate. The dependence of the i-V response on pressure is due to the disruption of cation and anion distributions at equilibrium within the nanopore. Because the flow rate is proportional to the third power of the nanopore orifice radius, the pressure-driven flow can eliminate rectification in nanopores with radii of ∼200 nm but has a negligible influence on rectification in a smaller nanopore with a radius of ∼30 nm. The experimental results are in qualitative agreement with predictions based on finite-element simulations used to solve simultaneously the Nernst-Planck, Poisson, and Navier-Stokes equations for ion fluxes in a moving electrolyte within a conical nanopore.
[Recombinant receptors for testing agonists and antagonists of VIP and PACAP receptors]. (1996)

VIP and PACAP are structurally related neuropeptides. They interact with multiple classes of receptors that have been cloned recently. These receptors may be divided into two main classes: the PACAP type I receptors with a high affinity for PACAP and a low affinity for VIP and the PACAP type II receptors (with a high affinity for PACAP and VIP). Five different forms of the PACAP type I receptors are described and result from an alternative splicing of the messenger. Two distinct forms (VIP1 and VIP2 receptors) of the PACAP type II receptors are described. Considering this high number of variants and the coexistence of several variants in the same cell, the development of cell lines expressing a single type of receptor was required for the testing of selective agonists and antagonists. However, limits in the interpretation of the results obtained in the cell lines expressing the recombinant receptors were obvious: discovery of unusual receptor states and unusual coupling of cellular effectors when a high number of receptors was expressed.
Diagnosis of typhoid fever using a string capsule device (1984)

Cultures were made from blood, bone marrow, stool and duodenal contents (obtained with string capsules) from 36 patients with bacteriologically proven typhoid fever on admission to hospital. Duodenal content cultures proved to be as sensitive in diagnosis (86%) as bone marrow (75%) and more effective than blood (42%) and stool (26%) cultures in recovery of Salmonella typhi. The sensitivity of duodenal content cultures was not modified by the duration of illness at admission or by previous antibacterial therapy. Even on the seventh day of effective treatment with chloramphenicol, the culture of duodenal contents remained positive in 8 of 17 patients, whereas salmonellae were isolated from stool cultures in only 2 of the same patients. The results obtained with the string capsule, together with the simplicity, economy and acceptability of the procedure, the fact that it can be performed with minimal facilities and the advantages of bacteriological recovery for antibiotic sensitivity testing, suggest that its adoption would be very helpful in efforts to control this disease.
A mutant human histocompatibility leukocyte antigen DR molecule associated with invariant chain peptides. (1994)

From a human histocompatibility leukocyte antigen (HLA)-DR/DQ hemizygous, B lymphoblastoid progenitor, we isolated a cell line, 10.24.6, with a DR alpha missense mutation (96P-->96S), which results in an N-linked carbohydrate addition at position 94 in the DR alpha 2 domain. Several features of 10.24.6 cells suggest that the mutation disrupts normal intracellular formation of peptide/DR complexes. The mutant HLA-DR dimers, though expressed at the cell surface, lack the conformation of the mature, peptide-loaded class II molecules of the progenitor cell, as assessed by their loss of binding of certain antibodies and by the lack of stability in detergent (sodium dodecyl sulfate) solution. In addition, presentation of endocytosed antigen to HLA-DR-restricted T cells is defective in the mutant, but can be restored by transfection of a wild type DRA gene. Assays with synthetic peptides indicate that the 10.24.6 phenotype is not due to an intrinsic inability of the mutant DR molecules to bind peptides. Therefore, to directly evaluate peptide occupancy of the mutant molecules, we analyzed acid-eluted, HLA-DR-associated peptides. The predominant species from the 10.24.6 mutant is a nested set of invariant chain (Ii)-derived peptides that are undetectable in the DR eluate from progenitor cells. The region of DR alpha altered in the mutant molecules is thus implicated in normal formation of peptide/DR complexes. Further, the same set of Ii peptides associated with the DR molecules is present in the eluate from an antigen presentation mutant with a defect in an major histocompatibility complex (MHC)-linked gene. These results suggest that DR molecules in 10.24.6 and in certain presentation mutants are affected at the same or related steps in class II molecule biosynthesis, raising the possibility that class II molecules interact with an MHC-encoded accessory molecule during antigen presentation.