gebhart/patrepeval huggingface dataset:
Fibrin(ogen) mediates acute inflammatory responses to biomaterials. (1993)

Although "biocompatible" polymeric elastomers are generally nontoxic, nonimmunogenic, and chemically inert, implants made of these materials may trigger acute and chronic inflammatory responses. Early interactions between implants and inflammatory cells are probably mediated by a layer of host proteins on the material surface. To evaluate the importance of this protein layer, we studied acute inflammatory responses of mice to samples of polyester terephthalate film (PET) that were implanted intraperitoneally for short periods. Material preincubated with albumin is "passivated," accumulating very few adherent neutrophils or macrophages, whereas uncoated or plasma-coated PET attracts large numbers of phagocytes. Neither IgG adsorption nor surface complement activation is necessary for this acute inflammation; phagocyte accumulation on uncoated implants is normal in hypogammaglobulinemic mice and in severely hypocomplementemic mice. Rather, spontaneous adsorption of fibrinogen appears to be critical: (a) PET coated with serum or hypofibrinogenemic plasma attracts as few phagocytes as does albumin-coated material; (b) in contrast, PET preincubated with serum or hypofibrinogenemic plasma containing physiologic amounts of fibrinogen elicits "normal" phagocyte recruitment; (c) most importantly, hypofibrinogenemic mice do not mount an inflammatory response to implanted PET unless the material is coated with fibrinogen or the animals are injected with fibrinogen before implantation. Thus, spontaneous adsorption of fibrinogen appears to initiate the acute inflammatory response to an implanted polymer, suggesting an interesting nexus between two major iatrogenic effects of biomaterials: clotting and inflammation.
Host: vector systems for gene cloning in Clostridium. (1988)

The genus Clostridium contains some of the most toxic bacteria known to man (e.g., Clostridium tetani, Clostridium botulinum) as well as solvent-producing organisms of biotechnological interest (e.g., Clostridium acetobutylicum). Developments within the areas of plasmid vector construction and plasmid delivery methodology now provide the opportunity for applying recombinant DNA technology to this important group of bacteria.
Evaluating Image Retrieval (2005)

We present a comprehensive strategy for evaluating image retrieval algorithms. Because automated image retrieval is only meaningful in its service to people, performance characterization must be grounded in human evaluation. Thus we have collected a large data set of human evaluations of retrieval results, both for query by image example and query by text. The data is independent of any particular image retrieval algorithm and can be used to evaluate and compare many such algorithms without further data collection. The data and calibration software are available on-line. We develop and validate methods for generating sensible evaluation data, calibrating for disparate evaluators, mapping image retrieval system scores to the human evaluation results, and comparing retrieval systems. We demonstrate the process by providing grounded comparison results for several algorithms.
Effects of intraoperative hyperthermia on peripheral nerves: Neurological and electrophysiological studies (1994)

The tolerance of peripheral nerves to heat may limit the heat dose which can be applied to tumours. This may be particularly important in intraoperative hyperthermia (IOHT) for pelvic and retroperitoneal tumours. Furthermore the effects of hyperthermia alone must be known before its effects can be assessed in combination with irradiation. In this study injury to sciatic nerves was evaluated in 30 beagle dogs for 1 year following IOHT. IOHT was performed using a water circulating hyperthermia device with multichannel thermometry system. Neurological and electrophysiological examinations were done before, during and after IOHT treatment. Electrophysiological examinations showed a significant decrease in sciatic nerve conduction velocity and potential amplitude immediately after 60 min of heating for all temperatures. The greatest decrease in conduction velocity was observed for a temperature of 45 degrees C. Full recovery of nerve conduction velocity was observed 3 weeks following hyperthermia for all dogs except for those exposed to 45 degrees C. Neurological findings correlated with electrophysiological results. All five dogs which had nerve exposed to 45 degrees C for 60 min had severe neurological changes, with recovery taking place between 3 and 11 months after treatment. Based on these results it appears that temperatures to the peripheral nerve exceeding 44 degrees C for 1 h are likely to cause significant, but not necessarily permanent, nerve injury.
Discovery of Highly Potent and Selective α4β2-Nicotinic Acetylcholine Receptor (nAChR) Partial Agonists Containing an Isoxazolylpyridine Ether Scaffold that Demonstrate Antidepressant-like Activity. Part II (2012)

In our continued efforts to develop α4β2-nicotinic acetylcholine receptor (nAChR) partial agonists as novel antidepressants having a unique mechanism of action, structure-activity relationship (SAR) exploration of certain isoxazolylpyridine ethers is presented. In particular, modifications to both the azetidine ring present in the starting structure 4 and its metabolically liable hydroxyl side chain substituent have been explored to improve compound druggability. The pharmacological characterization of all new compounds has been carried out using [(3)H]epibatidine binding studies together with functional assays based on (86)Rb(+) ion flux measurements. We found that the deletion of the metabolically liable hydroxyl group or its replacement by a fluoromethyl group not only maintained potency and selectivity but also resulted in compounds showing antidepressant-like properties in the mouse forced swim test. These isoxazolylpyridine ethers appear to represent promising lead candidates in the design of innovative chemical tools containing reporter groups for imaging purposes and of possible therapeutics.
Hypochlorous acid alters bronchial epithelial cell membrane properties and prevention by extracellular glutathione (2003)

In chronic inflammatory diseases of the airways, such as cystic fibrosis, hypochlorous acid (HOCl) generated by neutrophils is involved in airway injury. We examined the effects of HOCl on 16HBE14o- bronchial epithelial cells by bolus addition or by generation with glucose oxidase plus myeloperoxidase. HOCl produced both carbonyl formation of a discreet number of proteins and modification of surface targets that were recognized by an antibody raised against HOCl-modified protein. Bolus or enzymatically generated HOCl decreased transepithelial resistance, but surprisingly bolus HOCl also increased short-circuit current. Glutathione in lung epithelial lining fluid is an excellent scavenger of HOCl; however, glutathione content is lower in cystic fibrosis epithelial lining fluid due to deficient glutathione transport to the apical side of bronchial-tracheal epithelial cells (Gao L, Kim KJ, Yankaskas JR, and Forman HJ. Am J Physiol Lung Cell Mol Physiol 277: L113-L118, 1999). We found that alteration of the GSH content of apical fluid above 16HBE14o- cells was protective because all HOCl-induced changes were delayed or eliminated by exogenous glutathione within the physiological range. Extrapolating this to cystic fibrosis suggests that HOCl can alter cell function without destruction but that elevating glutathione could be protective.
Interactions between, and effectiveness of, power system stabilizers and FACTS device stabilizers in multimachine systems (2000)

In this paper it is shown that interactions occur between stabilizers in multimachine power systems, the stabilizers being power system stabilizers (PSSs), FACTS device stabilizers (FDSs) or both. The interactions, which are identified and quantified, may enhance or degrade the damping of certain modes of rotor oscillation. In particular, interactions between PSSs are found to adversely affect the damping of inter-area modes. The analysis of interactions also provides a practical means for quantifying and assessing simultaneously the relative effectiveness of both PSSs and FDS in damping the rotor modes of oscillation. This is achieved using a stabilizer damping contribution diagram. A theoretical basis is given for the analysis of interactions and the effectiveness of stabilizers; the practical significance and applications are illustrated using a case study on a 3-area, 400 state system having 28 generator groups and a number of FDSs. For systems of more than 600-700 states the modified Arnoldi method is used for eigenanalysis-based calculations.
Executive Summary: Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society (2016)

Abstract It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. These guidelines are intended for use by healthcare professionals who care for patients at risk for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), including specialists in infectious diseases, pulmonary diseases, critical care, and surgeons, anesthesiologists, hospitalists, and any clinicians and healthcare providers caring for hospitalized patients with nosocomial pneumonia. The panel's recommendations for the diagnosis and treatment of HAP and VAP are based upon evidence derived from topic-specific systematic literature reviews.
Mechanical, permeability, and degradation properties of 3D designed poly(1,8 octanediol‐co‐citrate) scaffolds for soft tissue engineering (2010)

Poly(1,8-octanediol-co-citric acid) (POC) is a synthetic biodegradable elastomer that can be processed into three-dimensional (3D) scaffolds for tissue engineering. We investigated the effect of designed porosity on the mechanical properties, permeability, and degradation profiles of the POC scaffolds. For mechanical properties, scaffold compressive data were fitted to a one-dimensional (1D) nonlinear elastic model, and solid tensile data were fitted to a Neohookean incompressible nonlinear elastic model. Chondrocytes were seeded on scaffolds to assess the biocompatibility of POC. Increased porosity was associated with increased degradation rate, increased permeability, and decreased mechanical stiffness, which also became less nonlinear. Scaffold characterization in this article will provide design guidance for POC scaffolds to meet the mechanical and biological parameters needed for engineering soft tissues such as cartilage.
Engineering Antigen-Specific T Cells from Genetically Modified Human Hematopoietic Stem Cells in Immunodeficient Mice (2009)

There is a desperate need for effective therapies to fight chronic viral infections. The immune response is normally fastidious at controlling the majority of viral infections and a therapeutic strategy aimed at reestablishing immune control represents a potentially powerful approach towards treating persistent viral infections. We examined the potential of genetically programming human hematopoietic stem cells to generate mature CD8+ cytotoxic T lymphocytes that express a molecularly cloned, "transgenic" human anti-HIV T cell receptor (TCR). Anti-HIV TCR transduction of human hematopoietic stem cells directed the maturation of a large population of polyfunctional, HIV-specific CD8+ cells capable of recognizing and killing viral antigen-presenting cells. Thus, through this proof-of-concept we propose that genetic engineering of human hematopoietic stem cells will allow the tailoring of effector T cell responses to fight HIV infection or other diseases that are characterized by the loss of immune control.
Proteolytic Pathways of Activation and Degradation of a Bacterial Phospholipase C during Intracellular Infection by Listeria monocytogenes (1997)

Listeria monocytogenes is a facultative intracellular bacterial pathogen that spreads cell to cell without exposure to the extracellular environment. Bacterial cell-to-cell spread is mediated in part by two secreted bacterial phospholipases C (PLC), a broad spectrum PLC (PC-PLC) and a phosphatidylinositolspecific PLC (PI-PLC). PI-PLC is secreted in an active state, whereas PC-PLC is secreted as an inactive proenzyme (proPC-PLC) whose activation is mediated in vitro by an L. monocytogenes metalloprotease (Mpl). Analysis of PI-PLC, PC-PLC, and Mpl single and double mutants revealed that Mpl also plays a role in the spread of an infection, but suggested that proPC-PLC has an Mpl-independent activation pathway. Using biochemical and microscopic approaches, we describe three intracellular proteolytic pathways regulating PCPLC activity. Initially, proPC-PLC secreted in the cytosol of infected cells was rapidly degraded in a proteasome-dependent manner. Later during infection, PCPLC colocalized with bacteria in lysosome-associated membrane protein 1-positive vacuoles. Activation of proPC-PLC in vacuoles was mediated by Mpl and an Mpl-independent pathway, the latter being sensitive to inhibitors of cysteine proteases. Lastly, proPC-PLC activation by either pathway was sensitive to bafilomycin A1, a specific inhibitor of vacuolar ATPase, suggesting that activation was dependent on acidification of the vacuolar compartment. These results are consistent with a model in which proPC-PLC activation is compartment specific and controlled by a combination of bacterial and host factors.
McDonald et al, 2014 PSCI - Study 2 Data (2014)

Datasets from Study 2 of the publication: McDonald, M.M., Donnellan, M.B., Lang, R. &amp; Nikolajuk, K. (2014). Treating prejudice with Imagery: Easier said than done? Psychological Science published online 6 February 2014. DOI: 10.1177/0956797613516010
ChemInform Abstract: MODIFICATION OF THE 2′‐POSITION OF PURINE NUCLEOSIDES‐ SYNTHESES OF 2′‐α‐SUBSTITUTED‐2′‐DEOXYADENOSINE ANALOGS (1977)

Abstract Aus dem Thionooxazolidin (I) erhält man über die Hg‐Verbindung (II) in guter Ausbeute das Pyrimidin‐Derivat (IVa), das zum 8‐Mercapto‐ara‐adenosin (V) reduziert und cyclisiert und anschließend zu (VI) entschwefelt werden kann.
Nitric Oxide Attenuates Neutrophil-Mediated Myocardial Contractile Dysfunction After Ischemia and Reperfusion (1996)

With the knowledge of NO as an antiadhesion molecule, we performed studies to investigate the effects of NO on postischemic polymorphonuclear leukocyte (PMN)-medicated myocardial contractile dysfunction. Studies were performed with isolated perfused rat hearts subjected to 20 minutes of global ischemia and 45 minutes of reperfusion. Human PMNs (50 million) were infused over the first 5 minutes of reperfusion, and the recovery of left ventricular function was compared with baseline values. Infusion of PMNs alone (n = 10) led to a 61% reduction in left ventricular developed pressure (LVDP) and a 57% reduction in the pressure-rate product (PRP) at 45 minutes of reperfusion. Infusion of an NO donor, CAS-754 (n = 9), resulted in 80.2 +/- 6.7% recovery of LVDP and 77.0 +/- 8.6% recovery of PRP. Treatment with L-arginine (2.5 mmol/L, n = 10) resulted in a similar improvement in the postischemic contractile state of the heart. In contrast, NG-nitro-L-arginine methyl ester (L-NAME) treatment (250 mumol/L, n = 10) resulted in an exacerbation of contractile dysfunction, as evidence by a 93% reduction in LVDP at 45 minutes of reperfusion and a 91% reduction in PRP. The deleterious effects of L-NAME were prevented by L-arginine coperfusion. We failed to observe any cardioprotective effects when NO or L-arginine was administered to hearts subjected to 25 minutes of ischemia and 45 minutes of reperfusion in the absence of PMNs. In conclusion, PMN-mediated myocardial contractile dysfunction is attenuated by NO and exacerbated by blockade of NO synthesis.
Clinical overview of the synucleinopathies (2003)

The term synucleinopathies is used to name a group of neurodegenerative disorders characterized by fibrillary aggregates of alpha-synuclein protein in the cytoplasm of selective populations of neurons and glia. These disorders include Parkinson's disease (PD), dementia with Lewy bodies (DLB), pure autonomic failure (PAF), and multiple system atrophy (MSA). Clinically, they are characterized by a chronic and progressive decline in motor, cognitive, behavioural, and autonomic functions, depending on the distribution of the lesions. Because of clinical overlap, differential diagnosis is sometimes very difficult. Parkinsonism is the predominant symptom of PD, but it can be indistinguishable from the parkinsonism of DLB and MSA. Autonomic dysfunction, which is an isolated finding in PAF, may be present in PD and DLB, but is usually more prominent and appears earlier in MSA. DLB could be the same disease as PD but with widespread cortical pathological states, leading to dementia, fluctuating cognition, and the characteristic visual hallucinations. The deposition of aggregates of synuclein in neurons and glia suggests that a common pathogenic mechanism may exist for these disorders. Even though synuclein may play an important role in disease development in these disorders, in light of the different symptom complex and prognosis and management issues that characterize each disorder, we think that the term synucleinopathy has little practical value as a diagnostic term for the clinician. Clinicians should attempt to reach standard clinical diagnosis on patients, such as PD, PAF, or MSA.
Supramolecular gels formed from multi-component low molecular weight species (2012)

Low molecular weight supramolecular gels consist of small molecules (gelators) that in an appropriate solvent self-assemble into nano- or micro-scale network structures resulting in the formation of a gel. Most supramolecular gels consist of two parts, namely the solvent and the gelator. However, the concept of multi-component supramolecular gels, in which more than one compound is added to the solvent, offers a facile way (e.g. by changing the ratio of the different components) to tailor the properties of the gel. The simplest multi-component gels consist of two components added to the solvent and are the most widely studied to date. There are three general classes of such multi-component gels that have been investigated. The first class requires all the added components to access the gel; that is, no component forms a gel on its own. A second class uses two (or more) gelators which can either co-assemble or self-sort into distinct assemblies and the final class consists of one (or more) gelator and one (or more) non-gelling additive which can impact the assembly process of the gelator and therefore the gel's properties.
Effects of Plasma Calcium Concentration on the Relative Proportion of Hormone and Carboxyl Fragments in Parathyroid Venous Blood* (1979)

The molecular nature of immunoreactivity in parathyroid venous blood, which was collected from anesthetized calves by surgical cannulation, was examined by gel filtration and RIAs with specificity for either the amino (N assay) or carboxyl (C assay) end of the hormone molecule. All samples contained immunoreactivity which eluted from the gel column (Bio-Gel P-100; 45 × 1.2 cm) coincident with radioiodinated purified parathyroid hormone (84 amino acids). This material reacted in both N and C assays. In addition to this, the effluent plasma immunoreactivity contained another component which eluted from the column after the radiolabeled hormone and was recognized only by the C assay. Very little of the latter type of material was found in hypocalcemic samples, but it represented an increased proportion of the total immunoreactivity in normocalcemic samples and this material was the predominant form of immunoreactivity in hypercalcemic samples. RIA of a series of samples of parathyroid venous plasma, collected sequentially from five anesthetized neonatal calves during induced alterations of plasma calcium concentration, revealed that the ratio of the concentration of C-reactive material to that of N-reactive material varied with plasma calcium concentration. The C:N ratio (ratio of carboxyl to amino immunoreactivity) of these samples increased from a value of about 1.3 during hypocalcemia to greater than 3 during hypercalcemia. These observations suggest that a fragment of parathyroid hormone, devoid of the aminoterminal portion of the molecule, originates in the parathyroid gland. The C:N ratios of peripheral plasma collected from three older conscious calves during induced alterations of plasma calcium concentration were similar to those observed in neonatal effluent plasma having an equivalent state of calcium concentration. It appears that both the secretion of carboxyl fragment(s) and the previously suggested postsecretory cleavage of parathyroid hormone by other organs may contribute to the carboxyl fragments found in the peripheral circulation. The similarity of the C:N ratios in peripheral and effluent plasma suggests that the secretion of fragments by the parathyroid gland contributes significantly to the concentration of carboxyl fragments in peripheral blood. This appears to be especially true during hypercalcemia, when the parathyroid gland secretes mostly fragments and only a small amount of intact hormone available for conversion to carboxyl fragment peripherally.
Role of Anti-Oxidants in Atherosclerosis: Epidemiological and Clinical Update (2005)

Low density lipoprotein (LDL) oxidative modification in the vascular wall seems to be a key factor in atherosclerosis development. Oxidised LDLs might recruit monocytes and favour their transformation into foam cells through a receptor-mediated intake (scavenger pathway). Moreover oxidised LDLs show cytotoxic potential which is probably responsible for endothelial cell damage and macrophage degeneration in the atherosclerotic human plaque. Following the oxidation hypothesis of atherosclerosis the role of natural antioxidants, i.e. Vitamin C, Vitamin E and carotenoids, has been investigated in a large number of epidemiological, clinical and experimental studies. Animal studies indicate that dietary antioxidants may reduce atherosclerosis progression, and observational data in humans suggest that antioxidant vitamin ingestion is associated with reduced cardiovascular disease, but the results of randomised controlled trials are mainly disappointing. It has been suggested that natural antioxidants may be effective only in selected subgroups of patients with high levels of oxidative stress or depletion of natural antioxidant defence systems. The favourable effects shown by some studies relating antioxidant dietary intake and cardiovascular disease, may have been exerted by other chemicals present in foods. Flavonoids are the ideal candidates, since they are plentiful in foods containing antioxidant vitamins (i.e. fruits and vegetables) and are potent antioxidants. Tea and wine, rich in flavonoids, seem to have beneficial effects on multiple mechanisms involved in atherosclerosis. Future studies should probably select patients in a context of high-oxidative stress / low-antioxidant defence, to verify if antioxidants may really prove useful as therapeutic anti-atherosclerotic agents.
A new vitreal drug delivery system using an implantable biodegradable polymeric device. (1994)

These results suggested that this device may be a potentially effective system to deliver drugs in the vitreous.