gebhart/patrepeval huggingface dataset:
Shedding of L-Selectin as a Mechanism for Reduced Polymorphonuclear Neutrophil Exudation in Patients With the Systemic Inflammatory Response Syndrome (1996)

Alterations in neutrophil L-selectin, not endothelial CAMs, are important in decreased neutrophil exudation. Reduced levels of neutrophil L-selectin associated with increased levels of serum L-selectin in patients with SIRS suggest premature intravascular shedding of neutrophil L-selectin. This would compromise the initial interaction between neutrophils and the endothelium, and, consequently, impede exudation.
CpG Oligodeoxyribonucleotides Rescue Mature Spleen B Cells from Spontaneous Apoptosis and Promote Cell Cycle Entry (1998)

Isolated murine splenic B cells undergo spontaneous apoptosis. Motifs containing unmethylated CpG dinucleotides in bacterial DNA or in synthetic oligodeoxynucleotides (ODN) are known to activate murine B cells. Now we show that ODN that induce spleen B cell cycle entry also inhibit spontaneous apoptosis in a sequence-specific fashion. Reversal of the CG to GC abolished activity. Methylation of the central cytosine decreased activity. When CpG is preceded by a cytosine or followed by a guanine, activity was abolished. Other substitutions at the same positions had no effect. Dose-response curves for apoptosis protection and G1 entry suggested that a uniform population of ODN recognition sites controlled downstream ODN effects. A CpG ODN with a nuclease-resistant phosphorothioate backbone (S-ODN) was also active, and increased the levels of c-myc, egr-1, c-jun, bclXL, and bax mRNA and c-Myc, c-Jun, Bax, and BclXL protein in spleen B cells. Levels of c-myb, myn, c-Ki-ras, and bcl2 mRNA remained unchanged. When protein synthesis was inhibited, at 16 h ODN-induced cell cycle entry was abolished and apoptosis protection was partially preserved. Under these conditions, c-Myc was still present, but c-Jun and BclXL were not detected. Our results suggest that CpG containing ODN motifs provide signals for both survival and cell cycle entry. Single base changes determine whether this signal proceeds through a rate-limiting step governing at least two steps in apoptosis (plasma membrane transition, DNA cleavage) and two phases of the cell cycle (G1 and S phase entry). This biologic action is associated with increased c-Myc, c-Jun, and BclXL expression.
Financement prive des infrastructures routieres (1996)

Africa faces a great challenge as it seeks to mobilize sufficient funds to build, improve, and maintain a network of high capacity freeways to serve the needs of the region's rapidly growing road transport industry. Given the acute shortage of government revenues, many governments increasingly turn to the private sector for assistance. In most cases, this will entail permitting the private sector to build and operate these roads under concession agreements. Under such an arrangement, the state will grant a concession company the right to finance, build, own, operate, and maintain public infrastructure for a given period, and to charge users for that service.
Identification of a functional role for lipid asymmetry in biological membranes: Phosphatidylserine-skeletal protein interactions modulate membrane stability (2002)

Asymmetric distribution of phospholipids is ubiquitous in the plasma membranes of many eukaryotic cells. The majority of the aminophospholipids are located in the inner leaflet whereas the cholinephospholipids are localized predominantly in the outer leaflet. Several functional roles for asymmetric phospholipid distribution in plasma membranes have been suggested. Disruption of lipid asymmetry creates a procoagulant surface on platelets and serves as a trigger for macrophage recognition of apoptotic cells. Furthermore, the dynamic process of phospholipid translocation regulates important cellular events such as membrane budding and endocytosis. In the present study, we used the red cell membrane as the model system to explore the contribution of phospholipid asymmetry to the maintenance of membrane mechanical properties. We prepared two different types of membranes in terms of their phospholipid distribution, one in which phospholipids were scrambled and the other in which the asymmetric distribution of phospholipids was maintained and quantitated their mechanical properties. We documented that maintenance of asymmetric distribution of phospholipids resulted in improved membrane mechanical stability. The greater difficulty in extracting the spectrin-actin complex at low-ionic strength from the membranes with asymmetric phospholipid distribution further suggested the involvement of interactions between aminophospholipids in the inner leaflet and skeletal proteins in modulating mechanical stability of the red cell membrane. These findings have enabled us to document a functional role of lipid asymmetry in regulating membrane material properties.
Electrical and materials properties of ZrO2 gate dielectrics grown by atomic layer chemical vapor deposition (2001)

Structural and electrical properties of gate stack structures containing ZrO2 dielectrics were investigated. The ZrO2 films were deposited by atomic layer chemical vapor deposition (ALCVD) after different substrate preparations. The structure, composition, and interfacial characteristics of these gate stacks were examined using cross-sectional transmission electron microscopy and x-ray photoelectron spectroscopy. The ZrO2 films were polycrystalline with either a cubic or tetragonal crystal structure. An amorphous interfacial layer with a moderate dielectric constant formed between the ZrO2 layer and the substrate during ALCVD growth on chemical oxide-terminated silicon. Gate stacks with a measured equivalent oxide thickness (EOT) of 1.3 nm showed leakage values of 10−5 A/cm2 at a bias of −1 V from flatband, which is significantly less than that seen with SiO2 dielectrics of similar EOT. A hysteresis of 8–10 mV was seen for ±2 V sweeps while a midgap interface state density (Dit) of ∼3×1011 states/cm eV was determined from comparisons of measured and ideal capacitance curves.
Heat capacity changes and hydrophobic interactions in the binding of FK506 and rapamycin to the FK506 binding protein. (1992)

Differential interactions among nonpolar moieties at protein/ligand interfaces, and of these nonpolar groups with water, collectively termed hydrophobic interactions, are widely believed to make important energetic contributions to the stability of protein/ligand complexes. Quantitative estimates of hydrophobic interactions, and an evaluation of their structural basis, are essential for obtaining structure-based predictions of the free energies of binding for the purpose of drug design. Two largely nonpolar, immunosuppressive agents, FK506 and rapamycin, each bind with high affinity to a common hydrophobic pocket on a small peptidylproline cis-trans isomerase known as FK506 binding protein (FKBP-12) and inhibit its activity. In an effort to elucidate the structural features of these ligands responsible for the observed energetics, we have undertaken an investigation of the thermodynamics of binding of FK506 and rapamycin to FKBP-12. Enthalpies of binding have been determined by high-precision titration calorimetry over a range of temperature, allowing estimates of heat capacity changes. By analyzing the distribution of changes in solvent-accessible surface area upon binding of FK506 to FKBP-12 from crystallographic data, it is found that 99% of the net surface buried upon binding involves nonpolar groups. This leads to a heat capacity change of FK506 binding, normalized to the amount of nonpolar surface, of -0.40 +/- 0.02 cal.K-1.mol-1.A-2 (1 cal = 4.18 J), a value similar to that obtained for the aqueous dissolution of hydrophobic substances. Our observations are discussed in view of the general nature of hydrophobic interaction processes.
Sperm protein 17 is expressed in human nervous system tumours (2006)

The frequency of expression and non-uniform cell distribution of Sp17 suggest that it cannot be used as a unique immunotherapeutic target in NS cancer. However, our results do show the immunolocalisation of Sp17 in a proportion of NS tumour cells, but not in their non-pathological counterparts. The emerging complex function of Sp17 makes further studies necessary to clarify the link between it and immunopositive cells.
Lookup table-based inverse model for determining tissue optical properties (2008)

We present a lookup table based-inverse model for determining tissue optical properties from steady-state diffuse reflectance spectra that is valid for fiber-based probe geometries with close source-detector separations and tissues with low albedos.
Bisbenzylisoquinolines as modulators of chloroquine resistance in Plasmodium falciparum and multidrug resistance in tumor cells (1996)

Ten naturally occurring bisbenzylisoquinolines (BBIQ) and two dihydro derivatives belonging to five BBIQ subgroups were evaluated in vitro for their ability to inhibit Plasmodium falciparum growth and, in drug combination, to reverse the resistance to chloroquine of strain FcB1. The same alkaloids were also assessed in vitro for their potentiating activity against vinblastine with the multidrug-resistant clone CCRF-CEM/VLB, established from lymphoblastic acute leukemia. Three of the BBIQ tested had 50% inhibitory concentrations of less than 1 microM. The most potent antimalarial agent was cocsoline (50% inhibitory concentration, 0.22 microM). Regarding the chloroquine-potentiating effect, fangchinoline exhibited the highest biological activity whereas the remaining compounds displayed either antagonistic or slight synergistic effects. Against the multidrug-resistant cancer cell line, fangchinoline was also by far the most active compound. Although there were clear differences between the activities of tested alkaloids, no relevant structure-activity relationship could be established. Nevertheless, fangchinoline appears to be a new biochemical tool able to help in the comprehension of the mechanism of both chloroquine resistance in P. falciparum and multidrug resistance in tumor cells.
Highly Branched Block Copolymers: Design, Synthesis, and Morphology (1999)

Several new approaches to biodegradable dendritic aliphatic block copolymers are described, including hyperbranched and dendrimer-like star structures. The hyperbranched polymers were obtained by the co-condensation of different AB2 macromonomers. The macromonomers were prepared by ring-opening polymerization (ROP) of either ε-caprolactone, l-lactide, or various substituted lactones using the benzyl ester of 2,2‘-bis(hydroxymethyl)propionic acid as initiator. Catalytic hydrogenation of the benzyl ester generated the requisite acid functional AB2 macromonomer. The second route utilizes a new type of molecular architecture, denoted as dendrimer-like star polymers. These block copolymers are described by a radial geometry where the different layers or generations are comprised of high molecular weight polymer emanating from a central core. With this architecture, more control in the placement of the different blocks is afforded over the hyperbranched analogue. As a means of imparting desirable mechanical properties to the dendritic copolymers, a series of new substituted lactones were prepared. The use of such monomers prevents crystallization of the poly(lactone), allowing dendritic polyesters with a range of mechanical properties from thermoplastic elastomers to rubber toughened systems, depending on the relative composition of the two components. The synthesis, characterization, and morphology of these new copolymers are discussed.
Some teratogenic properties of ethanol and acetaldehyde in C57BL/6J mice: Implications for the study of the fetal alcohol syndrome (1983)

To investigate the teratogenic effect of acute alcohol exposure, pregnant C57BL/6J mice were exposed to 25% ethanol (either two doses of 2.9g/kg or one dose 5.8g/kg) during the organogenic period either by intraperitoneal injections or by intubation. The incidence of malformations varied according to (1) the stage of embryonic development at the time of exposure, (2) the route of administration of the alcohol, and (3) the amount of alcohol given and the time period over which it was administered. Oral doses of alcohol were teratogenic although less so than the same dose given intraperitoneally, and two intraperitoneal doses four hours apart produced significantly more malformation than the same two doses six hours apart. The primary metabolite of alcohol, acetaldehyde, was also investigated for its teratogenicity. It was found that one or two doses of four percent acetaldehyde (0.32g/kg), administered intraperitoneally were teratogenic. A further attempt was made to raise blood acetaldehyde levels by exposing mice to disulfiram, an inhibitor of acetaldehyde dehydrogenase, prior to administration of alcohol. The disulfiram pretreatment did not increase the malformation rate. Treatment with alcohol on day 7 or 8 caused a variety of facial abnormalities, some of which were comparable to those seen in children with fetal alcohol syndrome. Exposure on day 9 or 10 resulted in limb defects. The results suggest that one or more episodes of heavy maternal drinking at critical periods in pregnancy may severely damage the embryo and may produce many features of the fetal alcohol syndrome.
Membrane protein variations associated with in vitro passage of Borrelia burgdorferi (1996)

Borrelia burgdorferi, the causative agent of Lyme disease, undergoes a loss in virulence with repeated passage in vitro. Defining the changes which occur after conversion to avirulence may assist in identifying virulence factors and mechanisms of pathogenesis. We have used a cross-adsorption technique and two-dimensional nonequilibrium pH gradient electrophoresis to compare virulent (low-passage) and avirulent (high-passage) variants of B. Burgdorferi B31. Using cross-adsorbed rabbit sera to probe immunoblots, we identified 10 low-passage-associated proteins (relative molecular masses of 78, 58, 49, 34, 33, 28, 24, 20, and 16 kDa) unique to the virulent strain B31. Cross-adsorbed human serum detected five proteins of similar sizes (78, 58, 34, 28, and 20 kDa), suggesting that several of of these proteins were expressed during human infection. By probing inner and outer membranes, two proteins (58 and 33 kDa) that localized specifically to the outer membrane were observed. An additional low-passage-associated protein (28 kDa) was identified when outer membranes from low- and high-pressure variants of strain B31 were compared by two-dimensional nonequilibrium pH gradient electrophoresis.
Die Europäische Verfassung — Eine Bilanz aus kommunaler Perspektive (2006)

AuszugIn der Erklärung des Europäischen Rates von Laeken vom Dezember 2001 waren sich die Staats- und Regierungschefs einig, dass sich die Europäische Union „50 Jahre nach ihrer Gründung an einem Scheideweg, einem entscheidenden Moment in ihrer Geschichte befinde“. Mit einer für politische Erklärungen ausgesprochen ungewöhnlichen Offenheit konstatierten die EU-Mitgliedstaaten seinerzeit, dass die Europäische Union dringend grundlegender Reformen bedürfe, um auch in einem erweiterten Europa noch bürgernah regieren zu können. Die Menschen hätten in der EU allzu oft das Gefühl, dass über „ihre Köpfe hinweg“ regiert werde. Eine grundlegende Reform sollte also die EU bürgernäher machen. Und der Weg dorthin sollte über einen Europäischen Grundlagenvertrag eröffnet werden, der schon bald als Entwurf einer „Europäischen Verfassung“ in aller Munde war.
Combined Modality Treatment of Glioblastoma Multiforme: The Role of Temozolomide (2006)

Despite of improvements in the biological and molecular characterization of glioblastoma multiforme and studies of factors associated with tumor growth and progression, this type of malignant astroglial brain tumor is still difficult to treat. The present article reviews established and emerging prognostic and predictive factors and their potential influence on future therapeutic efforts. Recent developments in standard treatment options (surgery, radiotherapy and chemotherapy) are summarized. The integration of the oral cytotoxic agent temozolomide into current treatment protocols of postoperative combination therapy with radiation and drugs is discussed, especially in the context of the recently published randomized trial of the EORTC/NCIC, which showed that radiotherapy plus concomitant and adjuvant temozolomide significantly improved progression-free and overall survival over radiotherapy alone. The study also provided hypotheses about the subgroups, which are most likely to benefit from this reasonably well tolerated regimen. In a subset of patients, investigation of MGMT promoter methylation in tumor tissue was performed. Survival was shorter in patients with unmethylated promoter in both study groups. Patients with methylated promoter treated with radiotherapy had a median survival of 15 months, those treated with radiation plus temozolomide of 22 months (p=0.007). In the unmethylated group, the difference in median survival was only 1 month (p=0.06). Especially for these patients, alternative treatments need to be developed. The optimum schedule of temozolomide administration and the influence of combinations with additional antineoplastic agents remains to be studied. Early results of clinical trials addressing these issues are presented.
Local and systemic activity of the polysaccharide chitosan at lymphoid tissues after oral administration (2005)

Chitosan is a cationic polysaccharide derived from the partial deacetylation of chitin, which exhibits particular properties: interacts with negatively charged sites on the cell surface; changes the permeability of intestinal epithelium, enhancing the uptake of peptides and proteins; and activates leukocytes. Antigens coadministered or encapsulated with the polysaccharide show improved mucosal and systemic humoral immune responses, although the mechanism is poorly understood. Herein, we characterized in Peyer's patches mesenteric lymph nodes and spleen molecular events triggered after oral administration of chitosan in the absence of protein antigen. Sixteen hours after feeding, we studied the uptake and distribution of the polysaccharide, the phenotype of recruited antigen-presenting cells (APC), the induction of cytokines such as tumor necrosis factor alpha, interleukin (IL)-12, IL-4, IL-10, and transforming growth factor-beta (TGF-beta), and the activation of T lymphocytes. We show here that the uptake of chitosan at inductive mucosal sites involves CD11b/c+ APC and that chitosan feeding increases the percentage of OX62+ dendritic cells, which up-regulate the major histocompatibility complex class II antigens without changing the expression of costimulatory CD80 or CD86 molecules. The polysaccharide elicits the release of IL-10 as well as the expression of IL-4 and TGF-beta in mucosa, and in spleen, the activation of CD3+ T cells occurs. Our results demonstrate that chitosan acts by enhancing the T helper cell type 2 (Th2)/Th3 microenvironment in the mucosa. A single dose of this polysaccharide exhibits local and systemic effects, and its activity could be relevant in the maintenance of the intestinal homeostasis.
Insights into Seeing and Grasping: Distinguishing the Neural Correlates of Perception and Action (2002)

Vision contributes to both perception and visuomotor control, and it has been suggested that many higher brain structures specialize in one or the other function. An alternative view, presented here, is that most higher brain areas participate in both visuomotor and perceptual functions. In the anterior frontal cortex, for example, the activity of one population of neurons reflects perceptual reports about a visual stimulus, whereas the activity of an intermingled population reflects movements aimed at the same stimulus. Similarly, posterior parietal and inferior temporal areas appear to function in both visual perception and visuomotor control. Visuomotor signals in higher order cortical areas could contribute to the perception of one's own action. They also might reflect the existence of two systems for visual information processing: one stressing accuracy for the control of movement and the other generating hypotheses about the world.
Binding of small molecules to an adaptive protein–protein interface (2003)

Understanding binding properties at protein-protein interfaces has been limited to structural and mutational analyses of natural binding partners or small peptides identified by phage display. Here, we present a high-resolution analysis of a nonpeptidyl small molecule, previously discovered by medicinal chemistry [Tilley, J. W., et al. (1997) J. Am. Chem. Soc. 119, 7589-7590], which binds to the cytokine IL-2. The small molecule binds to the same site that binds the IL-2 alpha receptor and buries into a groove not seen in the free structure of IL-2. Comparison of the bound and several free structures shows this site to be composed of two subsites: one is rigid, and the other is highly adaptive. Thermodynamic data suggest the energy barriers between these conformations are low. The subsites were dissected by using a site-directed screening method called tethering, in which small fragments were captured by disulfide interchange with cysteines introduced into IL-2 around these subsites. X-ray structures with the tethered fragments show that the subsite-binding interactions are similar to those observed with the original small molecule. Moreover, the adaptive subsite tethered many more compounds than did the rigid one. Thus, the adaptive nature of a protein-protein interface provides sites for small molecules to bind and underscores the challenge of applying structure-based design strategies that cannot accurately predict a dynamic protein surface.
The pathogenesis of tendinopathy. A molecular perspective (2003)

There are many publications that discuss the aetiology, diagnosis and treatment of the various forms of tendinopathy, but few are based on conclusive scientific evidence. The pathogenesis of tendinopathy is difficult to study because tendon biopsies are rarely obtained before a tendon has ruptured. There are interesting comparisons with animal tendinopathy, particularly in the equine athlete, although many animal models do not accurately reflect the human condition—the tendon lesions usually heal. However, the application of biochemical and molecular techniques to the study of both animal and human tendinopathy has led to a greater understanding of these common and disabling conditions. This article summarizes current knowledge of the pathogenesis of tendinopathy, with particular emphasis on the molecular pathology of the tendon matrix.
Using HTML 3.2 (1996)

From the Publisher:
User-Friendly means you can create HTML documents that include text, graphics, multimedia, and links to other Internet services; easily add tables and lists to your Web pages; organize your Web pages with frames; discover how to manage your Web pages with style sheets; create HTML documents for both Netscape Navigator and Microsoft Internet Explorer 3.0; add dynamic Java applets to spice up your standard HTML; and turn your HTML document into a mini program with JavaScript.
Wound Biofilm and Therapeutic Strategies (2016)

Since the turn of the millennium, an evolving body of scientific and clinical evidence indicates that biofilm is implicitly linked to delayed wound healing and infection. Currently, wound anti-biofilm strategies rely on non-specific wound bed preparation techniques involving physical debridement and cleansing, and innovative technologies designed to specifically manage biofilm have only just begun to emerge. The first output of anti-biofilm research and product development in wound care show great promise for patients, clinicians and healthcare institutions. The aim of this chapter is to address the current clinical biofilm problem, describe existing and emerging strategies to combat wound biofilm and review the available evidence.