gebhart/patrepeval huggingface dataset:
Development of Naturally-Derived Biomaterials and Optimization of Their Biomechanical Properties (2007)

Summary S ince surgeons have endeavored to repair the human body, there has been a need for materials to suit that purpose. Not surprisingly, many of the first materials used for these procedures were of natural sources either xenogenic or allogenic. When synthetic materials became more prevalent in the early 20th century, a huge market for synthetic implants was realized. The advantages, and disadvantages, of using naturally-derived biomaterials were known only in general terms and the ensuing decades saw only a modest increase in usage of these materials. Not until the recent times, have naturalderived biomaterials been explored as facilitators and promoters of healing and regeneration. Today, biomaterials of all types are being used for everything from wound dressing to tendon and ligament repair. Extensive experimentation has been undertaken to identify the composition, mechanical properties, and in vivo response of naturally-derived biomaterials. In this review, we present a brief history of naturally-derived biomaterials, their recent applications, and methods of characterization. Methods to optimize the morphological and mechanical properties of such a biomaterial for individual applications are then discussed in detail.
Network synchronisation of radio ports in wireless personal communications (1992)

Time synchronisation of fixed radio ports is crucial in digital wireless personal communications. The Letter describes a centralised approach for providing each synchronisation over the wireline distribution network. Various existing digital transmission facilities are considered as candidates for the wireline transport interface. Issues related to the possible impacts of this approach on evolving distribution network architectures are discussed.
Purification and Molecular Cloning of an 8R-Lipoxygenase from the Coral Plexaura homomalla Reveal the Related Primary Structures of R- and S-Lipoxygenases (1996)

Lipoxygenases that form S configuration fatty acid hydroperoxides have been purified or cloned from plant and mammalian sources. Our objectives were to characterize one of the lipoxygenases with R stereospecificity, many of which are described in marine and freshwater invertebrates. Characterization of the primary structure of an R-specific enzyme should help provide a new perspective to consider the enzyme-substrate interactions that are the basis of the specificity of all lipoxygenases. We purified an 8R-lipoxygenase of the prostaglandin-containing coral Plexaura homomalla by cation and anion exchange chromatography. This yielded a colorless enzyme preparation, a band of approximately 100 kDa on SDS-polyacrylamide gel electrophoresis, and turnover numbers of 4000 min-1 of 8R-lipoxygenase activity in peak chromatographic fractions. The full-length cDNA was cloned by PCR using peptide sequence from the purified protein and by 5'- and 3'-rapid amplification of cDNA ends. The cDNA encodes a polypeptide of 715 amino acids, including over 70 amino acids identified by peptide microsequencing. A peptide presequence of 52 amino acids is cleaved to give the mature protein of 76 kDa; the difference from the estimated size by SDS-PAGE implies a post-translational modification of the P. homomalla enzyme. All of the iron-binding histidines of S-lipoxygenases are conserved in the 8R-lipoxygenase. However, the C-terminal amino acid is a threonine, as opposed to the isoleucine that provides the carboxylate ligand to the iron in all known S-lipoxygenases. These results establish that the 8R-lipoxygenase is related in primary structure to the S-lipoxygenases. A model of the basis of R and S stereospecificity is described.
Pioneering spirit (2000)

In recent years, learning disability nurses across the country have re-focused their practice in order to meet the health needs of people with learning disabilities. Success often depends on the singlemindedness of individual nurses who cannot stand by and see people with learning disabilities get a second class service. In this article, Julie Wilkins describes how she is breaking the mould to bring a vital service to a small but significant group of women with learning disabilities
Self-limitation in the surface segregation of Ge atoms during Si molecular beam epitaxial growth (1991)

Self-limitation in the surface segregation of Ge atoms in the Si epitaxial overlayers arising from the surface bond geometry on Si(100) during molecular beam epitaxy has been investigated theoretically. It was found that Ge surface segregation is strongly limiting when the Ge concentration exceeds 0.01 monolayer. As a result of this self-limitation, segregation profiles of Ge in Si overlayers are found to decay nonexponentially in the growth direction with a kink in the profile around 3×1020 cm−3, which is in close agreement with the experimental observation. The kinetic barrier of the Ge surface segregation is estimated to be 1.63±0.1 eV.
Cell-derived microvesicles and cancer. (2009)

Blood and other body f luids contain cell-derived microvesicles. The presence of microvesicles in cancer patients was already noticed in the late 1970s. Since then, the prothrombotic state in cancer patients has invariably been associated with the presence of such microvesicles. More recently, a growing body of evidence supports an important contribution of microvesicles to cancer cell survival, invasiveness and metastases. Here, we will present an overview of the many contributions of microvesicles to cancer development and progression. In addition, their role in risk stratification and treatment of cancer patients is discussed.
Dicer, Drosha, and Outcomes in Patients with Ovarian Cancer (2008)

Our findings indicate that levels of Dicer and Drosha mRNA in ovarian-cancer cells have associations with outcomes in patients with ovarian cancer.
Inhibiting the TLR4‐MyD88 signalling cascade by genetic or pharmacological strategies reduces acute alcohol‐induced sedation and motor impairment in mice (2011)

These data provide new evidence that TLR4-MyD88 signalling is involved in the acute behavioural actions of alcohol in mice.
Human plasmacytoid dendritic cells efficiently cross-present exogenous Ags to CD8+ T cells despite lower Ag uptake than myeloid dendritic cell subsets (2012)

In human peripheral blood, 4 populations of dendritic cells (DCs) can be distinguished, plasmacytoid dendritic cells (pDCs) and CD16(+), CD1c(+), and BDCA-3(+) myeloid DCs (mDCs), each with distinct functional characteristics. DCs have the unique capacity to cross-present exogenously encountered antigens (Ags) to CD8(+) T cells. Here we studied the ability of all 4 blood DC subsets to take up, process, and present tumor Ags to T cells. Although pDCs take up less Ags than CD1c(+) and BDCA3(+) mDCs, pDCs induce potent Ag-specific CD4(+) and CD8(+) T-cell responses. We show that pDCs can preserve Ags for prolonged periods of time and on stimulation show strong induction of both MHC class I and II, which explains their efficient activation of both CD4(+) and CD8(+) T cells. Furthermore, pDCs cross-present soluble and cell-associated tumor Ags to cytotoxic T lymphocytes equally well as BDCA3(+) mDCs. These findings, and the fact that pDCs outnumber BDCA3(+) mDCs, both in peripheral blood and lymph nodes, together with their potent IFN-I production, known to activate both components of the innate and adaptive immune system, put human pDCs forward as potent activators of CD8(+) T cells in antitumor responses. Our findings may therefore have important consequences for the development of antitumor immunotherapy.
Fermentation of Glucose, Fructose, and Xylose by Clostridium thermoaceticum : Effect of Metals on Growth Yield, Enzymes, and the Synthesis of Acetate from CO 2 (1973)

Clostridium thermoaceticum ferments xylose, fructose, and glucose with acetate as the only product. In fermentations with mixtures of the sugars, xylose is first fermented, then fructose, and last, glucose. Fructose inhibits the fermentation of glucose, and this inhibition appears to be due to a repression of the synthesis of an enzyme needed for glucose utilization. Addition of metals to the culture medium increases the cell yield drastically from about 7 to 18 g per liter, and Y(glucose) values between 40 and 50 are obtained. According to the postulated pathways of the fermentation of glucose and synthesis of acetate from CO(2) by C. thermoaceticum, 3 mol of ATP are available as energy for growth. Thus a Y(adenosine 5'-triphosphate) of 13 to 16 is obtained. Because the normal Y(ATP) value is 10.5, this could mean that an additional source of ATP is available by an unknown mechanism. The addition of metals also increases the nicotinamide adenine dinucleotide phosphate-dependent formate dehydrogenase activity, the overall reaction ((14)CO(2) --> acetate), and the incorporation of the methyl group of 5-methyltetrahydrofolate into acetate. These reactions are catalyzed very efficiently by cells harvested in early growth, whereas cells obtained at the end of a fermentation have very low formate dehydrogenase activity and capacity to incorporate CO(2) into acetate. The following enzymes involved in the synthesis of acetate from CO(2) and in the metabolism of pyruvate are present in extracts of C. thermoaceticum: 10-formyltetrahydrofolate synthetase, 5,10-methenyltetrahydrofolate cyclohydrolase, 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methylenetetrahydrofolate reductase, phosphate acetyltransferase, and acetate kinase. These enzymes are not or are very little affected by the addition of metals to the growth medium. The amount of corrinoids in cells from early growth is low, whereas it is high in cells harvested late in growth. The opposite is found for the activity of delta-aminolevulinate dehydratase, which is high at the beginning of growth and low at the end.
Multiplex RT-PCR Amplification of HIV Genes to Create a Completely Autologous DC-Based Immunotherapy for the Treatment of HIV Infection (2008)

This study describes a strategy to overcome patient to patient viral diversity enabling strain-independent RT-PCR amplification of RNAs encoding sequence divergent quasispecies of Gag, Vpr, Rev and Nef from small volumes of infectious plasma. The approach allows creation of a completely autologous therapy that does not require advance knowledge of the HIV genomic sequences, does not have yield limitations and has no intact virus in the final product. The simultaneous use of autologous viral antigens and DCs may provoke broad patient-specific immune responses that could potentially induce effective control of viral loads in the absence of conventional antiretroviral drug therapy.
Expert system for predicting protein localization sites in gram‐negative bacteria (1991)

Abstract We have developed an expert system that makes use of various kinds of knowledge organized as “if‐then” rules for predicting protein localization sites in Gram‐negative bacteria, given the amino acid sequence information alone. We considered four localization sites: the cytoplasm, the inner (cytoplasmic) membrane, the periplasm, and the outer membrane. Most rules were derived from experimental observations. For example, the rule to recognize an inner membrane protein is the presence of either a hydrophobic stretch in the predicted mature protein or an uncleavable N‐terminal signal sequence. Lipoproteins are first recognized by a consensus pattern and then assumed present at either the inner or outer membrane. These two possibilities are further discriminated by examining an acidic residue in the mature N‐terminal portion. Furthermore, we found an empirical rule that periplasmic and outer membrane proteins were successfully discriminated by their different amino acid composition. Overall, our system could predict 83% of the localization sites of proteins in our database.
Split GFP complementation assay: a novel approach to quantitatively measure aggregation of tau in situ: effects of GSK3β activation and caspase 3 cleavage (2007)

To quantitatively measure tau aggregation in situ, we established a cell model system using a split green fluorescence protein (GFP) complementation assay. In this assay the more aggregated the protein of interest the lower the GFP fluorescence. Tau microtubule-binding domain constructs, whose aggregation characteristics have been described previously (Khlistunova et al. 2006), were used to validate the assay. The aggregation-prone construct exhibited the lowest GFP intensity whereas the aggregation-resistant construct showed the highest GFP intensity. To examine the role of glycogen synthase kinase 3beta (GSK3beta) activity and caspase 3 cleavage on tau aggregation, GFP complementation of full length (T4), caspase-cleaved (T4C3), and pseudophosphorylated at S396/S404 (T4-2EC) tau was examined in the presence of an active or a kinase-dead GSK3beta. Extensive phosphorylation of T4 by GSK3beta resulted in increased GFP intensity. T4C3 showed neither efficient phosphorylation nor a significant GFP intensity change by GSK3beta. The GFP intensity of T4-2EC was significantly reduced by GSK3beta accompanying its presence in the sarkosyl-insoluble fraction, thus demonstrating that T4-2EC was partitioning into aggregates. This indicates that if the majority of tau is phosphorylated at S396/S404, in combination with increased GSK3beta activity, tau aggregation is favored. These data demonstrate that split GFP complementation may be a valuable approach to determine the aggregation process in living cells.
An obligatory α‐helical amino acid residue (1973)

Abstract Stereochemical studies predict that α‐amino isobutyric acid, one of the amino acids found in antibiotics, can fold only into left‐ or righthanded α‐helical conformations. Such residues will direct chain folding and should be useful in synthetic analogs of protein sequences to increase helix stability.
Determination of the Low-Frequency Linear Electro-Optic Effect in Tetragonal BaTiO_3† (1965)

The magnitude of the linear electro-optic effect at 5461 Å in single-crystal barium titanate has been determined in the temperature range from 5° to 120°C. The low-frequency or stress-free values were obtained for r42 and rc = r33 − (na/nc)3r13. The polarimetric measurement did not separate r33 from r13. The quantity r42 was found to vary as Ka, the dielectric constant effective for the a-directed electric field. Similarly, rc was approximately proportional to KcPs, the product of the “c” dielectric constant and spontaneous polarization, but did not rise quite as fast as KcPs with increasing temperature. The difference was outside experimental uncertainty. The values found at 25°C were rc = 1.08×10−8 cm/V; r42=16.4×10−8 cm/V.
Diameter dependence of exciton-phonon interaction in individual single-walled carbon nanotubes studied by microphotoluminescence spectroscopy (2006)

We have investigated the diameter dependence of the exciton luminescence linewidth in individual single-walled carbon nanotubes (SWNTs) by means of microphotoluminescence ($\ensuremath{\mu}$-PL) spectroscopy. The line shapes of $\ensuremath{\mu}$-PL spectra for single SWNTs suspended on a patterned Si substrate at room temperature can be fitted by single Lorentzian functions. It is found that the $\ensuremath{\mu}$-PL linewidth depends strongly on the diameter of SWNTs and the exciton-phonon interaction is enhanced with a decrease of the diameter.
Enteric Targeting Through Enteric Coating (2001)

The aim of this review is to provide an up-to-date technological and pharmacological assessment of an ‘‘old’’ but still widely used dosage form, the enteric-coated tablet, capsule, or granule.Enteric-coated formulations are suitable vehicles to modify the release of active substances such that release at speciﬁc target areas within the gastrointestinal (GI) tract can be affected, although the effectiveness of this methodology has long been a point of discussion. Kra¨mer et al. [1] investigated the use of enteric coatings of 261 pharmaceutical products (Figure 1). The intended use included taste (9.6%) and odor (1%) masking, drug stabilization (31%), protection against local irritation (38%), and release directed to deﬁned segments in the digestive tract (51%).
The characteristics of inhibition of protein synthesis by double-stranded ribonucleic acid in reticulocyte lysates (1975)

All types of double-stranded RNA (DSRNA) tested inhibit protein synthesis in rabbit reticulocyte lysates. The inhibition is characterized by its strongly biphasic kinetics, and can be enhanced by preincubation of the lysate with dsRNA in the absence of protein synthesis. Only properly and extensively matched dsRNA (greater than about 50 base pairs) has this property; no form of DNA, single-stranded RNA or even RNA-DNA hybrids act as inhibitors in this way. The cause of the inhibition appears to be a failure of initiator tRNA to associate with native ribosomal subunits in the initiation process (Darnbrough, C., Hunt, T., and Jackson, R. J. (1973) Biochem. Biophys. Res. Commun. 48, 1556-1564). We have shown that this block is not accompanied by stable association of dsRNA with the ribosomes. There are several reasons to believe that the mechanism of action of dsRNA may be complex with the possible involvement of at least one catalytic step. First, the lysate is inhibited by levels of dsRNA at which ribosomes are present in 100-fold excess over base pairs of dsRNA present. Second, high concentrations of dsRNA (greater than 10 mug per ml) are not inhibitory, but can in some, but not all experiments, reverse the inhibition caused by lower levels of dsRNA. Third, a lysate which has been inhibited by dsRNA, when mixed with a fresh lysate will inhibit synthesis in the mixture much more severely than would be expected from the concentration of dsRNA now present. These results indicate that low levels of dsRNA promote the formation of an inhibitor which may exist in two forms: one that is reversible by high levels of dsRNA and one that is irreversible.
Clinical potential of lixisenatide once daily treatment for type 2 diabetes mellitus (2013)

The glucagon-like peptide (GLP)-1 receptor agonist lixisenatide (Lyxumia(®)) was approved for marketing by the European Medicines Agency in February 2013 and has been evaluated in a clinical study program called GetGoal. Lixisenatide activates the GLP-1 receptor and thereby exercises the range of physiological effects generated by GLP-1, which consist of increased insulin secretion, inhibition of glucagon secretion, and decreased gastrointestinal motility alongside the promotion of satiety. In the GetGoal study program, lixisenatide demonstrated significant reductions in glycated hemoglobin (HbA1c), and fasting and postprandial plasma glucose compared with placebo. The effect on glycemia was evident, with both monotherapy and in combination with insulin and various oral antidiabetic agents. Furthermore, a general trend towards reduced bodyweight was reported. In head-to-head trials with the other GLP-1 receptor agonists (exenatide and liraglutide) on the market, lixisenatide demonstrated a superior effect with respect to reduction in postprandial plasma glucose and had a tendency towards fewer adverse events. However, lixisenatide seemed to be less efficient or at best, equivalent to exenatide and liraglutide in reducing HbA1c, fasting plasma glucose, and bodyweight. The combination of a substantial effect on postprandial plasma glucose and a labeling with once daily administration separates lixisenatide from the other GLP-1 receptor agonists. The combination of basal insulin, having a lowering effect on fasting plasma glucose, and lixisenatide, curtailing the postprandial glucose excursions, makes sense from a clinical point of view. Not surprisingly, lixisenatide is undergoing clinical development as a combination product with insulin glargine (Lantus(®)). At present the main place in therapy of lixisenatide seems to be in combination with basal insulin. A large multicenter study will determine the future potential of lixisenatide in preventing cardiovascular events and mortality, in patients with type 2 diabetes and recent acute coronary syndrome.
Selective Recruitment of Immature and Mature Dendritic Cells by Distinct Chemokines Expressed in Different Anatomic Sites (1998)

DCs (dendritic cells) function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. They then leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. This suggestive link between DC traffic pattern and functions led us to investigate the chemokine responsiveness of DCs during their development and maturation. DCs were differentiated either from CD34(+) hematopoietic progenitor cells (HPCs) cultured with granulocyte/macrophage colony-stimulating factor (GM-CSF) plus tumor necrosis factor (TNF)-alpha or from monocytes cultured with GM-CSF plus interleukin 4. Immature DCs derived from CD34(+) HPCs migrate most vigorously in response to macrophage inflammatory protein (MIP)-3alpha, but also to MIP-1alpha and RANTES (regulated on activation, normal T cell expressed and secreted). Upon maturation, induced by either TNF-alpha, lipopolysaccharide, or CD40L, DCs lose their response to these three chemokines when they acquire a sustained responsiveness to a single other chemokine, MIP-3beta. CC chemokine receptor (CCR)6 and CCR7 are the only known receptors for MIP-3alpha and MIP-3beta, respectively. The observation that CCR6 mRNA expression decreases progressively as DCs mature, whereas CCR7 mRNA expression is sharply upregulated, provides a likely explanation for the changes in chemokine responsiveness. Similarly, MIP-3beta responsiveness and CCR7 expression are induced upon maturation of monocyte- derived DCs. Furthermore, the chemotactic response to MIP-3beta is also acquired by CD11c+ DCs isolated from blood after spontaneous maturation. Finally, detection by in situ hybridization of MIP-3alpha mRNA only within inflamed epithelial crypts of tonsils, and of MIP-3beta mRNA specifically in T cell-rich areas, suggests a role for MIP-3alpha/CCR6 in recruitment of immature DCs at site of injury and for MIP-3beta/CCR7 in accumulation of antigen-loaded mature DCs in T cell-rich areas.