bluuebunny/crossref_metadata_2025 huggingface dataset:
Poly (L-Lysine Citramide), a Water-Soluble Bioresorbable Carrier for Drug Delivery: Aqueous Solution Properties of Hydrophobized Derivatives
Authors: Gautier Sandrine , Boustta M. , Vert Michel
Published: July 2017

Poly(L-lysine citramide) (PLCA), a novel biocompatible and bioresorbable water-soluble polymer, was designed as a macromolecular prodrug carrier coupling drugs to hydrophilic carriers generally leads to hydrophobization of the precursor macromolecules which then form micelle-like water-dispersed aggregates or are completely insoluble. To study these phenomena, hydrophobization of PLCA was investigated. Alkyl groups (C7 and C12) were covalently attached to the lysine of the polymer which was prepared by either step-growth polymerization or selective hydrolysis of alkylated derivatives. Hydrophobized macromolecules formed nanosized multimolecular aggregates in aqueous media. The size of these aggregates was influenced by concentration, ionic strength, degree of ionization, alkyl substitution and alkyl group length.
Controlled Release of FITC-BSA from Polymer Coated Gelatin Microspheres
Authors: Rao Jyoti K. , Rao K. Panduranga
Published: July 2017

Gelatin microspheres containing the model protein, FITC-BSA, were prepared using the polymer dispersion technique. These microspheres were characterized for their thermal stability using differential scanning calorimetry. In order to prolong the release of the entrapped FITC-BSA, the microspheres were coated with a synthetic and biodegradable polymer, polycaprolactone. The polymer coated microspheres were characterised using infrared spectroscopy and scanning electron microscopy. In vitro release studies indicated that the release rate of FITC-BSA decreased with the increase in the coating concentration of the polymer.
Cytotoxicity and Anticancer Activity of Macromolecular Prodrugs of 5-Fluorouracil
Authors: Nichifor Marieta , Schacht Etienne H. , Seymour Leonard W. , Anderson Dave , Shoaibi Mahmood
Published: July 2017

Polymeric conjugates of 5-fluorouracil (5-FU) were synthesized by covalent attachment of tetrapeptide chains with 2-(5-fluorouracil-1-yl)glycine ethyl ester [Gly(FU)OEt] as the C-terminus, to poly(ethylene glycol) (PEG) and dextran (Dex). Cytotoxicity of these conjugates was compared with free 5-FU against the murine colorectal carcinoma cell line C26. All the conjugates displayed lower cytotoxicity than 5-FU. The chemical structure and the configuration of the tetrapeptide chains influenced the activity of the conjugates. Materials containing the tetrapeptide Gly-Phe-Gly-Gly(FU)OEt (l,d), with Dex-based conjugates were more cytotoxic than the analogue PEG-based conjugate. PEG-Gly-Phe-Gly-Gly(FU)OEt (l,d) administered to mice at doses of 150 and 250 mg 5-FU equivalent/kg, following by inoculation of C26 tumor cells, mediated much less toxicity than equivalent doses of free 5-FU. The anticancer activity achieved using free and polymer-bound drugs were comparable, although decreased toxicity of the conjugate should facilitate administration of increased doses with improved efficacy.
Oligopeptides as an Oral Delivery System II. Effect of Amino Acid Sequences on Aggregation Behavior
Authors: Haratake Mamoru , Zhao Ruifeng , Ottenbrite Raphael M.
Published: July 2017

The effect of amino acid sequences on the aggregation and the subsequent sphere formation behavior of tetrapeptides, pEE(a)X(y) involving glutamic acid (E), phenylalanine (F), tyrosine (Y), alanine (A), and leucine (L) were investigated by light scattering and light microscopy. At 0.1 M pEE(a)Y(y)Y and pEE(a)F(y)F showed similar pH and concentration-dependent aggregation behaviors. These tetrapeptides also showed similar aggregation profiles in the presence of macromolecular drugs. Only pEE(a)F(y)F produced discrete spheres in the presence of protein drugs. Neither pEE(a)A(y)A nor pEE(a)L(y)L gave aggregates even at 0.1 M at pH 2. Consequently, the amino acids terminal positions are important in the aggregation characteristics of the tetrapeptides.
Hydrolysis and Antibacterial Activity of Polymers Containing 8-Quinolinyl Acrylate
Authors: Bankova M. , Manolova N. , Markova N. , Radoucheva T. , Dilova K. , Rashkov I.
Published: July 2017

The hydrolytic release of 5-chloro-8-hydroxyquinoline (HQ) from 5-chloro-8-quinolinylacrylate (AQ) containing polymers was studied under physiological under conditions (pH 7.2 and 37°C) as well as in acidic and alkaline medium. The hydrolysis rate was influenced by autocatalytic process with participation by quinolinyl groups as well as by neighboring groups. For copolymers of AQ and acrylamide (AM), the release rate increased with increasing pH, temperature, and the content of hydrophilic monomer. Copolymers of AQ and N-vinylpyrrolidone (VP) exhibit a lower rate of HQ release because of steric hindrance of the hydrolysis site and the influence of the alternating VP-AQ sequences which contribute to the enhanced hydrophobicity of the copolymer. The antimicrobial activity of the copolymers was found to be related to their hydrolysis behavior. The attachment of a biologically active agent to a macromolecular carrier can prolong its effect.
Regulation of Biocalcification of Bovine Pericardial Tissue b Grafting Poly(Glycidyl Methacrylate-Butylacrylate) Copolymers
Authors: Shanthi C. , Rao K. Panduranga
Published: July 2017

Calcification is the principal cause of failure of glutaraldehyde cross-linked bovine pericardium used as cardiac valve substitutes. Young age, glutaraldehyde pretreatment, and mechanical factors are identified as the main causes of biocalcification. Glutaraldehyde pretreatment is believed to create void spaces in the fiber matrix increasing the availability of physical niches for calcification. In the present paper, glutaraldehyde cross-linked pericardial tissue (GCPC) was filled by grafting polymers with different properties which impart flexibility to the pericardium. These polymers included glycidyl methacrylate (GMA) and butylacrylate (BA) initiated by ceric ion technique. Tensile strength, shrinkage temperature, and differential scanning thermogram were recorded for the glutaraldehyde cross-linked tissues before and after polymer grafting. Calcification studies were done subdermally in rat models. The best anticalcification properties were observed in tissues grafted with GMA: BA monomers of mole ratio of 15:7.2 and initiator concentration of 7.5 x 10-3 mol L-1.
Healing of Burn Wounds and Managing Infection
Authors: Shalaby Marc , Shalaby Shalaby W.
Published: July 2017

This review covers the physiology of thermal injury and pathophysiology of burn wounds in terms of burn wound healing, wound infection, and strategies for controlling and preventing infection. Emerging trends relevant to wounds, such as the development of novel extrudable gel-forming bioabsorbable liquids, and tissue engineering are briefly discussed.
Biodegradable Poly[(Amino Acid Ester)phosphazenes] for Biomedical Applications
Authors: Lemmouchi Yahia , Schacht Etienne , Dejardin Stéphane
Published: July 2017

Polyphosphazene derivatives with amino acid ester side groups were prepared by reacting poly(dichlorophosphazene) with ethyl esters of amino acids and were characterized by 1H, 31P-NMR and DSC analyses. The in vitro rate of degradation of these polymers depended on the nature of the amino acids while introducing small amounts of depsipeptide ester co-substituents increased degradation rates. The rate of hydrolytic degradation of the poly[(organo)phosphazene] materials could be controlled by the amino acid ester by the depsipeptide ester side group content and by blending poly[(amino acid ester)phosphazenes] with poly[(amino acid ester)-co-(depsipeptide ester)phosphazenes]. Poly[(glycine ethyl ester)phosphazenes] prepared from poly[(dichloro)phosphazenes] degradation rates were independent of molecular weight. Degradations of polymer blends indicate that an intramolecular catalysis ofthe polymer by the pendent carboxylic acid.
A Hydrophobically Modified Bioadhesive Polymeric Carrier for Controlled Drug Delivery to Mucosal Surfaces
Authors: Inoue Tadaaki , Chen Guohua , Hoffman Allan S. , Nakamae Katsuhiko
Published: July 2017

We have synthesized and studied a new type of polymeric drugcarrier based on hydrophobically modified bioadhesive graft copolymers. Two different hydrophobic oligomers, an oligo(methyl methacrylate) (oMMA) and a random co-oligomer of MMA with hydroxyethyl methacrylate (HEMA) were separately grafted to a polyacrylic acid (PAAc) backbone. This system forms a physical hydrogel network containing hydrophobic domains. The in vitro release of hydrophilic drugs such as theophylline and a model protein drug, lysozyme, and moderately hydrophobic drugs such as propranolol hydrochloride has been investigated. The results suggest the existence of a macroporous structure at higher levels of oMMA grafting. The introduction of HEMA into the graft chain slowed the release of propranolol hydrochloride, which suggests that the release rate of a moderately hydrophobic drug could be controlled by adjusting the hydrophobicity of the grafted chain. In the case of release of lysozyme, a cationic protein used as a model protein drug, the graft copolymers of oMMA retained increasing amounts of the protein as the graft level increased. This supported the concept of formation of a macroporous structure at higher MMA graft levels, with a cationic protein such as lysozyme being attracted to and bound by the hydrophobic domain interfacial regions. The introduction of as little as 10 mol% of HEAIA into the graft chain gave rise to rapid and complete release of lysozyme.
Adhesion of Different Bacterial Strains to Low-Temperature Plasma Treated Biomedical Silicon Catheter Surfaces
Authors: Rad A. Yousefi , Ayhan H. , Pişkin E.
Published: July 2017

In this study, two different strains of five different bacteria were isolated and characterized. Contact angles were measured by a captive-bubble technique. Surface free energies were calculated from the contact angles and hydrophobicities were evaluated by p-xylene adhesion. The zeta potentials and surface charges of the bacteria were measured. The contact angles of the gram positive bacteria and gram negative bacteria were in the range of 48-69° and 43.5-55°, respectively. While corresponding surface free energies were in the limits of 45.4-51.6 erg·cm2 and 51.7-61.8 erg·cm−2, respectively. The p-xylene adhesions were parallel to hydrophobicity defined by contact angles, and 32.2-80.3% and 2.3-36.6% for the gram positive bacteria and gram negative bacteria, respectively. The zeta potentials for these bacteria were from −650.2 to + 17.5 mV and from -159.6 to -6.0 mV respectively. Most of the bacteria were negatively charged, except the CNS-2 and CPS-1 strains. In the second part of the study, the attachment of these bacteria to Si® catheters and to DMAEMA and AAc plasma treated Si® catheters were investigated. The hydrophobic bacteria attached best to the hydrophobic Si(r) catheter. Both plasma treatments caused significant drops in bacterial attachment in most cases. The effects of AAc plasma treatment were more pronounced.
New Biocidal N-Halamine-PEG Polymers
Authors: Eknoian M. W. , Worley S. D. , Harris J. M.
Published: July 2017

The synthesis and biocidal efficacies of two PEG-N-halamine polymers were reported. The N-halamines are classified as dichlorohydantoins and chloroimidazolidin-4-ones, which were attached to a methoxy-poly(ethylene glycol) terminated amine. A 1000 ppm solution of each N-halamine polymer was prepared in water and it was demonstrated that Staphylococcus aureus was inactivated (6 logs) when it was in contact with these polymeric solutions for ten minutes. The stability of these solutions was determined over prolonged periods of time, as well as the biocidal efficacies. These polymeric materials show commercial potential as surface active biocides if the polyethylene glycol) moiety can be anchored to a surface.
Synthesis and Characterization of N-(2-Hydroxypropyl)-Methacrylamide (HPMA) Copolymer-Emetine Conjugates
Authors: Dimitrijevic Sasa , Duncan Ruth
Published: July 2017

The plant alkaloid emetine has considerable potential as an antitumor agent, but early attempts to develop the compound clinically failed due to unacceptable dose limiting toxicity and poorly reproducible results. This study reports the synthesis and characterization of novel N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates containing emetine. The drug was linked to the polymer via biodegradable (Gly-Phe-Leu-Gly) and non-degradable (Gly-Gly) peptidyl linkers. HPMA-Gly-Gly emetine conjugate was found to contain 8% (w/w) of bound emetine, while emetine loading of HPMA-Gly-Phe-Leu-Gly-emetine was found to be 19% (w/w). Due to the change in cellular pharmacokinetics, polymer conjugates are invariably less toxic than free drug, in vitro and HPMA copolymer-emetine conjugates were no exception. Conjugates containing the biodegradable Gly-Phe-Leu-Gly linker displayed an IC50 of 90 μg/mL towards L1210 leukemia cells which is 225 less toxic than free emetine (IC50 = 0.4 μg/mL). Against B16F10 melanoma the conjugate was 60 times less toxic than free drug (IC50 of 300 and 5 μg/mL respectively). In contrast, the conjugate containing a non-biodegradable (Gly-Gly) linker showed very low or no activity in vitro. Although the conjugates showed no significant effect on the rate of tumor growth, the HPMA-Gly-Gly-emetine prodrug had a significant effect on the survival time of animals bearing L1210 tumors. Here we describe the first polymer conjugates containing emetine. Further studies are warranted to document the spectrum of antitumor activity, dose-limiting toxicity and pharmacokinetics of HPMA copolymer-emetine in vivo.
Bioartificial Polymeric Material: Poly(Ethylene Glycol) Crosslinked with Albumin. II: Mechanical and Thermal Properties
Authors: Gayet J. -Ch. , He P. , Fortier G.
Published: July 2017

A family of hydrogels based on the crosslinking of bovine serum albumin (BSA) and activated poly(ethylene glycol) (PEG), were characterized. The swelling process was found to be dependent on the molecular weight of the PEG used and on the OH/NH2 molar ratio of the reagents. These hydrogels performed a volume expansion from 266 to 554% when PEG with molecular weights from 3,350 to 20,000 were used. The volume expansion was greater when the OH/NH2 molar ratio increased. Some anisotropy occurred during swelling since thinner devices swelled more than thicker ones, due to the difference of constraints in the hydrogels structure. Mechanical studies showed that these hydrogels were highly deformable and presented good elastic behavior since they broke only after 80% deformation. At this point, they needed a compression force ranging from 165 to 456 g/cm2 to break. The differentiation of two kinds of water in these highly swollen hydrogels was performed using DSC studies at low temperature. Free water (i.e., bulk water) was found to be the predominant form which filled the network, .and bound water (i.e., water engaged in interactions with PEG) tended to form a trihydrate complex (three molecules of water per ethylene oxide repeated unit). Three forms of water with different evaporating rates were detected by DSC studies at high temperature. This other form of water may be important for maintaining the hydrogen's form.
Collagen and Fibronectin Carrying PHEMA Microbeads as Cell Affinity Sorbents
Authors: Ayhan H. , Pişkin E.
Published: July 2017

PHEMA microbeads, produced by suspension polymerization, were modified by the immobilization of a spacer (hexamethylene diamine, HMDA), and two proteins, collagen or fibronectin. Adsorption of collagen and fibronectin onto the plain and periodate oxidized PHEMA microbeads were similar; 0.05-0.1 mg of collagen and 0.04-0.05 mg of fibronectin per g of polymer, respectively. Collagen and fibronectin immobilization on PHEMA microbeads were studied at different temperatures, time and pH. The optimal values for immobilization were 0.1 mg/mL for fibronectin; and 0.25 mg/mL for collagen at 25°C for fibronectin and 4°C for collagen; pH 7 in 120 min. Both fibroblastic 3T3 and epithelial MDBK cells were attached to unmodified and modified microbeads. The attachments of both 3T3 and MDBK cells, to the fibronectin and collagen immobilized microbeads were more than 2000 cells per mg of polymer.
New N-Halamine Biocidal Polymers
Authors: Eknoian M. W. , Worley S. D.
Published: July 2017

A new series of N-halamine polymers has been synthesized and tested in granular form, on glass and as fiber substrates for efficacy at inactivating bacteria. Copolymers and grafted copolymers were prepared with 4-(alkyl acryloxymethyl)-4-ethyl-2-oxazolidinones and commercial monomers or polymers. These polymers are inexpensive to synthesize and are efficient biocides in granular form and as surface-coated disinfectants. They can be coated on glass, plastic, and fibrous materials, which gives them considerable potential as commercial disinfectants. They could be used for a variety of industrial, commercial, and medical applications.
Synthesis of Macromolecular Conjugates of a Urokinase Inhibitor: Amiloride
Authors: Pató Janos , Ulbrich Karel , Subr Vladimir , Baker Peter , Mezö Gábor , Hudecz Ferenc
Published: July 2017

Amiloride is a potent inhibitor of a urokinase type plasminogen activator which is involved in the invasive process of cancer cells leading to the initiation of metastasis. Synthesis, characterization and in vitro tests of four macromolecular conjugates of Amiloride are presented. One of them is a degradable derivative, HPMA-Gly-D,l-Phe-Leu-Gly-amiloride. In this case the in vitro release of Amiloride was monitored. Other conjugates are stable containing a new amiloride derivative, 6-aminohexyl amiloride [AHA], coupled to different polymeric carriers: a branched polypeptide, poly-[Lys(AcGlu1.0-D,l-Ala4.5)] [AcEAK], poly-[N-(2-hydroxy propyl) metacrylamide] [HPMA] and poly-[1-vinyl-2-pyrrolidone- co-maleic acid] [NVP MA]. Inhibition of uPA, plasminogen activation and proteinases secreted by cancer cells was measured as well as basement membrane degradation in vitro. Each amiloride AHA and the corresponding conjugates retained their activity in these experiments.
A Sensitive Assay System for the Determination of Poly(L-Lysine) Concentration Using Turbidometry
Authors: Ward Christopher M. , Fisher Kerry D. , Seymour Leonard W
Published: July 2017

The titration of albumin into poly(l-lysine) (pLL) dissolved in HEPES buffer (50 mM, pH 7.5) leads to a maximum turbidity that is directly proportional to the pLL concentration. This technique provides an accurate and precise determination of unknown pLL concentrations. Turbidity of albumin/pLL is decreased at high concentrations of salt and high pHs, suggesting that the albumin/pLL interaction has an electrostatic component. A standard ratio of albumin to pLL is required to attain maximum turbidity which is independent of pLL concentration. Increasing salt concentration or increasing pH decreases the albuminlpLL ratio required to attain maximum turbidity. An apparent association of log10 molecular weight with turbidity could provide a method to determine pLL molecular weights. A comparison of this method with two commercially available protein assays and size exclusion Catsec HPLC analysis revealed the turbidometric method to have the best correlation (R = 1.0) and the lowest detection limits (0.05 μg/mL limit of detection). This turbidometric analysis can also be used for the determination of polyethyleneimine concentrations (R = 1.0) and, possibly, other cationic polymers.
Conjugates of Semitelechelic Poly[N-(2-Hydroxypropyl)Methacrylamide] with Enzymes for Protein Delivery
Authors: Oupický David , Ulbrich Karel , Říhová Blanka
Published: July 2017

The semitelechelic poly[N-(2-hydroxypropyl)methacrylamide] [poly(HPMA)] with a carboxyl end group was prepared with 3-mercaptopropionic acid as a chain transfer agent. Bovine seminal ribonuclease (BSR) and α-chymotrypsin (ChT) were modified with various molecular weights of active poly(HPMA) succinimidyl ester by the reaction with the amino groups of the respective enzyme. The modification of ChT did not significantly change the activity or the substrate specificity of the conjugates towards low-molecular-weight tripeptidic substrates. However, modified ChT activity towards the corresponding poly(ethylene glycol)-based synthetic substrate was significant. The activity decreased as a result of the elevated steric hindrance to the active site of the polymer-modified enzyme. Similarly, the ChT conjugates completely lost their proteolytic activity toward native bovine serum albumin. The autolytic stability of ChT conjugates was improved and the proteolytic stability of the ChT and BSR conjugates substantially increased compared with the free enzymes. The modification of ChT with poly(HPMA) significantly decreased the immunogenicity of ChT conjugates depending on the molecular weight of the poly(HPMA) and the degree of enzyme substitution.
Synthesis and Some Properties of Poly(Alkylene Phosphorothioate)s Prepared from the Corresponding Poly(Alkylene H-Phosphonate)s
Authors: Kuznetsova O. , Kaluzynski K. , Lapienis G. , Pretula J. , Penczek S.
Published: July 2017

Several high molecular weight poly(alkylene phosphorothioate)s were synthesized by reacting poly(H-phosphonate)s with sulfur. The molecular weight of the resulting polymers are similar to the respective starting poly(alkylene H-phosphonate)s indicating that during sulfurization process no chain degradation occurred. The structure of poly(alkylene phosphorothioate)s was confirmed by the analysis of 1H, 13C and 31P NMR spectra.
Swelling and Thermal Properties of Poly(Vinyl Alcohol) Containing Hemoglobin Membranes
Authors: Vidal M. M.B. , Gil M. H. , Delgadillo I. , Chamarro J. Alonso
Published: July 2017

Poly(vinyl alcohol) (PVA), a hydrophilic polymer bearing hydroxyl functional groups, readily forms gels on the addition of a bifunctional agent such as glutaraldehyde. This gelation is caused by the formation of acetal bonds between the aldehyde groups and the hydroxyl groups, in the presence of HCL. The crosslink density is easily controlled by changing the concentration of glutaraldehyde, offering a way to control the total water content and, consequently, the permeability. Strong transparent films were obtained by drying these gels. These were suitable for supporting biologically active molecules, providing a viable, better alternative to the usual PVA gels which are physically crosslinked. To establish the relationship between their thermal properties and the occurrence of the physical or chemical gelling, their water vapor sorption and thermal behavior were investigated and compared. PVA/glutaraldehyde membranes were prepared with immobilized hemoglobin for bilirubin analysis. Assisted by the respective equilibrium swelling ratio and thermal stability data, it was found that, for these particular PVA/hemoglobin membranes, the occurrence of either chemical or physical crosslinking is mainly determined by the Hb/HCl ratio.
Relevance of Lactic Acid Generation to Mass Loss Profile for Polylactides
Authors: Burg K. J.L. , Laberge M. , Powers D. L. , Grimes L. , Shalaby S. W.
Published: July 2017

The bulk degradation of synthetic absorbable polyesters is thought to occur from the center of the material outward, and the degradation pattern is therefore attributed largely to the chemical composition of the material. It is hypothesized that this pattern may be altered by changing the morphological mapping of the material, i.e., by introducing molecular orientation into the system. A new solid state uniaxial orientation (SS-UO) process was used to orient two types of polylactide films. The films were exposed to a phosphate buffered solution, and the percent mass loss, dimensional change, and lactic acid release was monitored at predetermined times. The results, obtained using an analysis of variance and a linear correlation analysis, show that the release of lactic acid commences in the first month, but it is not until after 6 months that the oriented and nonoriented release rates differ. The mass loss is dependent on the polylactide type, as are the dimensional changes, while the lactic acid release is not material dependent. The mass loss may, in specific cases, be correlated to the lactic acid release.
Prison Litigation: From the 1960s to the 1990s
Authors: Mays G. Larry , Olszta Michelle
Published: July 2017

Prison litigation has been a critical issue for criminal justice and legal scholars, and for correctional practitioners for three decades. It generally is agreed that lawsuits filed by prison inmates and the attention given these suits by the federal courts have served to heighten the debate over the role of prisons in our society. Additionally, from an intergovernmental perspective, much concern has been expressed over the federal courts' role in supervising state prison operations. This article examines a number of legal and social issues that have been raised in prison litigation.
Synthesizing Values of Statistical Life for Energy-Environmental Policy Analysis
Authors: Huang J.P. , Ang B.W. , Poh K.L.
Published: July 2017

In energy and environmental investment or policy analysis, the valuation of human health risk is becoming an increasingly important issue. An often used measure of the human health risk is the value of the statistical life. However, estimates of this value tend to vary significantly from one study to another, due to the controversial nature of the problem. We use a recently proposed approach to synthesizing estimates of the value of life given in 19 different studies for the United States. The approach uses the Finite Mixture Distributions statistical technique and the Analytic Hierarchy Process multi-attribute analysis method. In the multi-attribute analysis, we assess the value of life estimates using nine criteria. We present the results obtained, and describe the uncertainty involved and some possible applications of the results.
The Use of Fertilizer and its Environmental Consequences
Authors: Uri Noel D.
Published: July 2017

The increase in the use of fertilizer in agricultural production has been associated with a substantial increase in agricultural productivity in the United States. This increase in fertilizer use has been driven by a variety of economic forces including variations in the price of output and changing relative factor prices. Associated with the increase in the use of fertilizer have been adverse environmental consequences that are not reflected in the costs and returns of agricultural production. That is, externalities exist whose cost need to be internalized. Because the use of fertilizer has been shown to respond to market forces, it is efficient to use the market to control the use of fertilizer. This can be done through, for example, the use of a fertilizer tax.
Research Priorities in Social Welfare Library and Information Work
Authors: Wilson T.D.
Published: July 2017

A questionnaire listing possible research projects in the field of social welfare information work was sent to 8 1 individuals representing practitioners in the field as well as librarians and information workers. The results were used to provide background information for participants in a Forum funded by the British Library Research and Development Depart ment and revealed some significant differences between priority judgements of practitioners and those of librarians and information workers. The technique employed can be regarded as a modification of the 'Delphi' technique and it is suggested that bringing respondents to the questionnaire together for the second 'round' of the investigation may have specific advantages in increasing mutual understanding among different interest-groups.
Factors affecting the Use of Seats in Academic Libraries
Authors: University of Cambridge Library Management Research Unit (LM
Published: July 2017

In 1971 the University Grants Committee wished to have information collected on the provision and use of reader places in university libraries, in order to be able to refine their 'building norms' for reader places in future university library buildings. Discussions were held with the Library Management Research Unit on the possibility of the information being eollected on a sponsored research basis, but the Steering Committee of the LMRU eventually decided to carry out the survey independently as part of its own programme. It was thought that a study of this type would certainly increase the knowledge of how libraries were being used and might provide a sound basis for examining the appropriateness of the UGC norms then in use. It was also decided to extend the survey into the field of polytechnic libraries. The large amount of data obtained by studying library use at 17 libraries and seating use at 21 libraries ( 11 academic institutions) shows that, although we have been able to collect detailed statistics of how libraries are being used, the factors underlying this use are very varied.

The main aspects suggested for study were the present utilization of seating ( peaks of use— when, where, why, and how great), curriculum, teaching methods and the influence of place, type of residence and subject on library use. The tables containing the data obtained from all aspects of the study are available from the LMRU.
Reviews : Local Library Co-operation
Authors: Clough E.A.
Published: July 2017

An article by T. D. Wilson on the chief findings of the final report on the DES Local Library Co-operation Project appeared in the July 1975 issue of the Journal. The following reviews are from the standpoint of a public and an academic librarian respectively.
'Library Instruction and the Development of the Individual' —a further comment
Authors: Hills P.J.
Published: July 2017

Dr. Hills's paper on library instruction and the development of the individual appeared in the October 1974 issue of the Journal of Librarianship, and a comment on it by Dr. M. B. Stevenson appeared in January 1975. Now Dr. Hills adds a further comment.
Review: Ubiquitination and de-ubiquitination: role in regulation of signaling by Toll-like receptors
Authors: Lowe Emily L. , Doherty Terence M. , Karahashi Hisae , Arditi Moshe
Published: July 2017

Signaling by Toll-like receptors (TLRs) has attracted accelerating attention over the past decade because of the central role of TLR signaling in both innate and adaptive immunity. In addition, TLR signaling is now increasingly implicated in a remarkably wide range of diseases that are either caused, or accompanied, by dysregulated inflammation. Much has been learned about the basic signaling framework and participants, as well as how signaling is turned off and fine-tuned. Here, we summarize key aspects of TLR signaling, focusing on interaction with the anti-inflammatory TGF-β signaling network. We propose that ubiquitination and de-ubiquitination of TLR pathway components may be a mechanism by which predominantly anti-inflammatory input is integrated into the host response to fine-tune inflammation in accordance with the needs of host defenses.
The molecular structure of the TLR3 extracellular domain
Authors: Bell Jessica K. , Botos Istvan , Hall Pamela R. , Askins Janine , Shiloach Joseph , Davies David R. , Segal David M.
Published: July 2017

Toll-like receptors (TLRs), type I integral membrane receptors, recognize pathogen associated molecular patterns (PAMPs). PAMP recognition occurs via the N-terminal ectodomain (ECD) which initiates an inflammatory response that is mediated by the C-terminal cytosolic signaling domain. To understand the molecular basis of PAMP recognition, we have begun to define TLR—ECD structurally. We have solved the structure of TLR3-ECD, which recognizes dsRNA, a PAMP associated with viral pathogens. TLR3-ECD is a horseshoe-shaped solenoid composed of 23 leucine-rich repeats (LRRs). The regular LRR surface is disrupted by two insertions at LRR12 and LRR20 and 11 N-linked carbohydrates. Of note, one side of the ECD is carbohydrate-free and could form an interaction interface. We have shown that TLR3-ECD binds directly to pI:pC, a synthetic dsRNA ligand, but not to p(dI):p(dC). Without a TLR3—dsRNA complex structure, we can only speculate how ligand binds. Analysis of the unliganded structure reveals two patches of basic residues and two binding sites for phosphate backbone mimics, sulfate ions, that may be capable of recognizing ligand. Mutational and co-crystallization studies are currently underway to determine how TLR3 binds its ligand at the molecular level.
DNA and RNA autoantigens as autoadjuvants
Authors: Busconi Liliana , Lau Christina M. , Tabor Abigail S. , Uccellini Melissa B. , Ruhe Zachary , Akira Shizuo , Viglianti Gregory A. , Rifkin Ian R. , Marshak-Rothstein Ann
Published: July 2017

AM14 B cells are a prototype for those low affinity autoreactive B cells that routinely mature as naïve cells in peripheral lymphoid tissues. These cells express a transgene-encoded receptor specific for IgG2a and can be effectively activated by immune complexes that incorporate either mammalian DNA or mammalian RNA that has been released from dead or dying cells. Activation depends on the ability of the B-cell receptor to deliver antigen to an internal vesicular compartment containing either Toll-like receptor-9 (TLR9) or TLR7. Since TLR9 and TLR7 are thought to recognize microbial DNA and RNA preferentially, it is important to determine under what conditions mammalian DNA and RNA become effective TLR ligands, and whether the determining factor is delivery or structure. This issue has been addressed by using IgG2a mAbs to deliver immune complexes preloaded with defined fragments of DNA or RNA, or by using modified ODNs/ORNs. The data demonstrate that only certain nucleic acid sequences or structures can induce autoreactive B-cell proliferation, even when delivery to the appropriate TLR compartment is facilitated by uptake through the B-cell receptor (BCR).
Factors involved in early in vitro endotoxin hyporesponsiveness in human endotoxemia
Authors: Nikola Kimmings A. , Pajkrt Dasja , Zaaijer Krista , Moojen Thybout M. , Meenan John K. , ten Cate Jan W. , van Deventer Sander J.H.
Published: July 2017

Sepsis and endotoxemia induce a state of early tolerance to the biological effects of endotoxin. Relatively little is known about the mechanisms or mediators involved in this endotoxin hyporesponsiveness. In this study endotoxin-induced TNF production of whole blood obtained at different time points from endotoxin challenged volunteers, and endotoxin- and PHA-induced TNF production by healthy PBMNCs in the presence of serum from endotoxin challenged volunteers were compared.

Endotoxin-induced TNF production by whole blood was found to be significantly reduced at 2 h after in vivo endotoxin administration, returning to baseline levels at t = 6 h. In addition, a reduction of TNF produced by healthy PBMNCs in the presence of post-endotoxin serum was observed. No correlation was found with the concentration of any of the well described anti-inflammatory mediators investigated nor with plasma levels of endotoxin-binding proteins.
Lipopolysaccharide-sensitivity of interferon-γ receptor deficient mice
Authors: Freudenberg Marina A. , Kopf Manfred , Galanos Chris
Published: July 2017

Interteron-γ receptor deficient (IFNγR-/-) and control wild-type (IFNγR+/+) mice were compared for their susceptibility to lipopolysaccharide (LPS) and tumor necrosis factor α (TNFα) before and after treatment with the LPSsensitizing agents D-galactosamine (D-GalN) or Propionibacterium acnes. Untreated and D-GalN-sensitized, IFNγR-/and IFNγR+/+ mice were comparable in their TNFα responses to LPS. Deficient and wild-type mice also exhibited a similar susceptibility to the lethal effects of LPS or TNFα which was enhanced by D-GalN treatment to a comparable extent. After treatment with P. acnes, the LPS and TNFα responsiveness remained unchanged in IFNγR-/- mice while in IFNγR+/+ mice they were enhanced up to 200-fold. These results indicate that IFN-γ mediates the LPS and TNFα hypersensitivity of P. acnes treated mice, while the normal sensitivity to LPS or TNFα in the presence or absence of D-GalN is IFN-γ independent.
Effect of succinylacetone administration on plasma nitrate levels of lipopolysaccharide-treated mice
Authors: Krijt Jan , Maruna Pavel , Stranska Pavla , Janousek Vaclav
Published: July 2017

Groups of 6 male BALB/c mice were treated twice daily for 4 days with 1000 mg/kg succinylacetone (SA), a heme biosynthesis inhibitor. Liver cytochrome P450 levels were slightly decreased and coumarin hydroxylase activity was increased from 124 ± 35 to 276 ± 37 pmol/mg/min. Renal cytochrome P450 content was decreased by SA treatment. SA had no effect on brain nitric oxide synthase activity.

Administration of lipopolysaccharide (LPS) increased plasma nitrite/nitrate levels, and pretreatment with SA for 72 h partially attenuated this effect. Plasma nitrate levels were 305 ± 67 μmol/l in LPS-injected mice and 116 ± 27 μmol/l in LPS-injected, succinylacetone pretreated mice. These results indicate that succinylacetone treatment interferes with the inducible nitric oxide synthase activity or with its activation pathway.
Reduction of the intestinal endotoxin pool by three different SDD regimens in human volunteers
Authors: van Saene J.J.M. , Stoutenbeek C.P. , van Saene H.K.F. , Matera G. , Martinez-Pellus A.E. , Ramsay G.
Published: July 2017

Aerobic Gram-negative bacilli (AGNB) carried in the gut by healthy individuals generate 1 mg of 'physiological' endotoxin per g of faeces. Successful eradication of AGNB from the gut would be expected to lead to a lowering of the intestinal endotoxin pool. This prompted us to evaluate the reduction of intestinal endotoxin in 6 healthy volunteers who each received 3 different oral antibiotic regimens. Regimen 1 was polymyxin E (600 mg/day), regimen 2 polymyxin E (400 mg/day) combined with tobramycin (320 mg/day) and regimen 3 pefloxacin (800 mg/day). Each regimen was separated by an antibiotic free period of 3 months. A faecal sample (minimally 2 g) was obtained from each volunteer, before treatment began and afterwards 3 times a week on alternating days (Monday, Wednesday, Friday) for 3 weeks. Each volunteer produced 30 samples, 10 each per oral antibiotic. The samples were serially diluted in nutrient broth for the colony count of AGNB, whilst endotoxin was measured using the classical Limulus amoebocyte lysate micro-assay. The base-line value of faecal AGNB was 10 3-4 colony forming units/g of faeces. All samples obtained on day 3 following antibiotic intake were negative for AGNB, and remained negative during antibiotic intake. The AGNB free carrier state was associated with a reduction in gut endotoxin. The reduction was approximately 10 ng (1 log) for polymyxin E and pefloxacin, whilst the combination of polymyxin/tobramycin significantly reduced the intestinal endotoxin concentrations from 1 mg to 100 ng in the gut; a reduction of 104. Although AGNB were killed by the three regimens, the 'free' endotoxin left in the gut was effectively neutralised by the combination polymyxin/tobramycin only. From a clinical point of view, gut-derived endotoxaemia may play a role in the systemic inflammatory response syndrome and hence the outcome, in critically ill intensive care patients. This study supports other work which indicates that mortality is significantly reduced in only those intensive care patients who received oral polymyxin/tobramycin.
Ultrastructural changes in bacterial lipopolysaccharide induced by human hemoglobin
Authors: Roth Robert I. , Wong Jinny S. , Hamilton Robert L.
Published: July 2017

Recently published studies showed that human hemoglobin (Hb) forms stable complexes with bacterial endotoxin (lipopolysaccharide, LPS), and that these complexes have much greater biological activity than LPS alone. LPS in LPS-Hb complexes has greater filterability, is less turbid, and has a lower sedimentation velocity compared to LPS alone, changes consistent with smaller LPS size. To further characterize the physical changes in LPS induced by Hb, we examined the ultrastructure of LPS alone and LPS-Hb complexes by negative staining. We studied two rough (Re) LPS and one smooth LPS, before and after incubation with purified human HbA0. Salmonella minnesota (Re) 595 LPS was visibly turbid, and was composed mostly of ribbon-like and mesh-like structures. In addition, this LPS contained large irregular membrane-like masses, and a few smaller discoidal particles. After incubation with Hb, none of the large mesh-like, ribbon-like or membrane-like structures remained; the resultant LPS particles were discoidal particles of 5-20 nm. Escherichia coli (Re) LPS alone was comprised predominantly of ribbon-like structures; after incubation with Hb, this LPS was comprised of circular membrane-like sheets (predominantly 40-200 nm). Smooth E. coli 055:B5 LPS alone contained heterogeneous particles of 10-100 nm. Most of the largest of these particles were disintegrated by the addition of Hb. The time course of Hb-induced LPS disaggregation was studied with S. minnesota LPS because the great turbidity of this LPS allowed us to monitor its disaggregation spectroscopically. Turbidity was decreased by 50% within approximately 5 h, and was not measurable by 25 h. We propose that the toxic domains of LPS (i.e. lipid A) are cryptic in native LPS aggregates and become exposed upon binding with Hb, thereby resulting in increased biological activity of LPS-Hb complexes compared to LPS alone.
Diagnosis and Management of a Postpyloric Foreign Body Causing Small Bowel Obstruction in an Infant
Authors: Bradford Victoria , Vadi Marissa , Carter Harmony
Published: July 2017

Foreign body ingestion is a common occurrence in the pediatric population and most ingestions resolve with little morbidity. Although radiopaque objects are easily identified on biplane radiographs, radiolucent objects may elude detection, delaying diagnosis. We report a case of a healthy 10-month-old infant who presented with a 5-day history of postprandial vomiting and imaging consistent with small bowel obstruction. On exploratory laparotomy, she was discovered to have a postpyloric foreign body requiring removal through an enterotomy.
Yellow Nail Syndrome With Dramatic Improvement of Nail Manifestations After Endoscopic Sinus Surgery
Authors: Hosokawa Yu , Kuboki Akihito , Mori Aya , Kanaya Hiroaki , Nakayama Tsuguhisa , Haruna Shinichi
Published: July 2017

Objectives:

Yellow nail syndrome (YNS) is a rare disease of unknown cause characterized by the triad of yellow nails, respiratory manifestations, and lymphedema. Although several therapies for YNS have been reported, there is no common consensus in the treatment. In this case report, we present a case of 56-year-old woman with YNS, whose nail manifestation was dramatically improved after endoscopic sinus surgery for the treatment of chronic rhinosinusitis.

Methods:

Endoscopic sinus surgery involving middle meatal antrostomy was performed for the case of YNS with chronic rhinosinusitis and bronchiectasis resistant to antibacterial drugs.

Results:

A month after the surgery, the patient’s nails eventually showed dramatic improvement.

Conclusions:

Otorhinolaryngologists should recognize that chronic rhinosinusitis can be a symptom of YNS, and that the aggressive treatment including surgical approach for chronic rhinosinusitis may be a useful in the control of nail manifestation in YNS.
By Way of Introduction: Methods in Studies of Bilingual First Language Acquisition
Authors: De Houwer Annick
Published: July 2017

This article considers methodological issues related to the study of children who are raised with two languages from birth. This area of study simultaneously belongs to the fields of child language and bilingualism research. Thus the methodological insights gained from these two fields should inform studies of bilingual first language acquisition (BFLA). In addition, there are a few methodological guidelines that apply specifically to the area of BFLA. Among these are the need to investigate unilingual utterances in the search for possible interlanguage effects in the acquisition process and the need to take into account very carefully the sociolinguistic setting in which data are collected. The need for terminological clarity puts into question the use of terms such as “language mixing,” “dominance” and “proficiency” in the field of BFLA.

This methodologically oriented article also functions as the introduction to the other contributions to this volume, which all raise methodological issues as well.
Bayesian varying-coefficient models using adaptive regression splines
Authors: Biller Clemens , Fahrmeir Ludwig
Published: July 2017

Varying-coefficient models provide a flexible framework for semi- and nonparametric generalized regression analysis. We present a fully Bayesian B-spline basis function approach with adaptive knot selection. For each of the unknown regression functions or varying coefficients, the number and location of knots and the B-spline coefficients are estimated simultaneously using reversible jump Markov chain Monte Carlo sampling. The overall procedure can therefore be viewed as a kind of Bayesian model averaging. Although Gaussian responses are covered by the general framework, the method is particularly useful for fundamentally non-Gaussian responses, where less alternatives are available. We illustrate the approach with a thorough application to two data sets analysed previously in the literature: the kyphosis data set with a binary response and survival data from the Veteran’s Administration lung cancer trial.
Professional Development of Educational Administration: Fundamentals and Applications
Authors: Bayer Manfred , Ortner Gerhard E.
Published: July 2017

The article describes first of all the aims and work of the Institute for Applied Studies in Educational Administration and Management at the North-Rhine -Westphalian Research Centre for Applied Studies in Educational Science (FEoLL) in Paderborn. The Institute works mainly on projects in applied educational research in the field of educational planning and organisation under the direction of the Education Minister of North-Rhine-Westphalia and the Federal Ministry of Education and Science. A representative sample of these projects will be described in detail to serve as examples. The inter-disciplinarily orientated research projects aim at concrete solutions to problems in the area of secondary education, in tertiary education and further education while considering not only the predominantly administrative-organisational aspects but also the socio-educational problems of the respective educational institutions together with the legal framework of educational policy and economy. Selected R & D results were documented and presented in such a way that they could be used for the initial and further training of head teachers and school administrators.
Experimental and Theoretical Study of the Thermoformability of Industrial Polymers
Authors: Laroche D. , Erchiqui F.
Published: July 2017

The processability of industrial polymers was experimentally and numerically investigated. The heating temperature of ABS and HIPS sheets was systematically varied in order to determine the minimum sheet temperature required for vacuum forming onto two different cavity moulds with acceptable thickness variations. Finite element simulations of the process using hyperelastic and viscoelastic constitutive equations were also performed in order to analyze the models' ability to predict thermoformability of polymers. Prediction of minimum required sheet temperature as well as the part thickness distribution were compared to experimental measurements.