bluuebunny/crossref_metadata_2025_split huggingface dataset:
Murine Syngeneic Graft-Versus-Host Disease Is Responsive to Broad-Spectrum Antibiotic Therapy
Authors: Brandon J. Anthony , Jennings C. Darrell , Kaplan Alan M. , Bryson J. Scott 
Published: February 2011

AbstractMurine syngeneic graft-versus-host disease (SGVHD) initiates colon and liver inflammation following lethal irradiation, reconstitution with syngeneic bone marrow transplantation, and therapy with the immunosuppressive agent cyclosporine A. Previous studies have demonstrated that the inducible disease is mediated by CD4+ T cells with increased reactivity of peripheral and liver-associated lymphocytes against intestinal microbial Ags. In the current report, studies were performed to analyze the specificity of the CD4+ T cell response of T cells isolated from diseased animals and to determine the in vivo role of the microbiota to the development of SGVHD. Increased major histocompatibility Ag (MHC) class II-restricted responsiveness of SGVHD CD4+ T cells against microbial Ags isolated from the ceca of normal animals was observed. The enhanced proliferative response was observed in the CD62L− memory population of CD4+ T cells. To determine the role of the bacterial microbiota in the development of murine SGVHD, control and CsA-treated bone marrow transplantation animals were treated with broad-spectrum antibiotics (metronidazole, ciprofloxacin) after transplantation. Cyclosporine A-treated animals that were given antibiotic therapy failed to develop clinical symptoms and pathological lesions in the target tissues characteristic of SGVHD. Furthermore, the reduction in intestinal bacteria resulted in the elimination of the enhanced antimicrobial CD4+ T cell response and significantly reduced levels of the inflammatory cytokines, IFN-γ, IL-17, and TNF-α. The elimination of the disease-associated inflammatory immune responses and pathology by treatment with broad-spectrum antibiotics definitively links the role of the microbiota and microbial-specific immunity to the development of murine SGVHD.
Granulysin Delivered by Cytotoxic Cells Damages Endoplasmic Reticulum and Activates Caspase-7 in Target Cells
Authors: Saini Reena V. , Wilson Christine , Finn Michael W. , Wang Tianhong , Krensky Alan M. , Clayberger Carol 
Published: February 2011

AbstractGranulysin is a human cytolytic molecule present in cytotoxic granules with perforin and granzymes. Recombinant 9-kDa granulysin kills a variety of microbes, including bacteria, yeast, fungi, and parasites, and induces apoptosis in tumor cells by causing intracellular calcium overload, mitochondrial damage, and activation of downstream caspases. Reasoning that granulysin delivered by cytotoxic cells may work in concert with other molecules, we crossed granulysin transgenic (GNLY+/−) mice onto perforin (perf)- or granzyme B (gzmb)-deficient mice to examine granulysin-mediated killing in a more physiologic whole-cell system. Splenocytes from these animals were activated in vitro with IL-15 to generate cytolytic T cells and NK cells. Cytotoxic cells expressing granulysin require perforin, but not granzyme B, to cause apoptosis of targets. Whereas granzyme B induces mitochondrial damage and activates caspases-3 and -9 in targets, cytotoxic cell-delivered granulysin induces endoplasmic reticulum stress and activates caspase-7 with no effect on mitochondria or caspases-3 and -9. In addition, recombinant granulysin and cell-delivered granulysin activate distinct apoptotic pathways in target cells. These findings suggest that cytotoxic cells have evolved multiple nonredundant cell death pathways, enabling host defense to counteract escape mechanisms employed by pathogens or tumor cells.
The Role of Heat Shock Protein 70 in Mediating Age-Dependent Mortality in Sepsis
Authors: McConnell Kevin W. , Fox Amy C. , Clark Andrew T. , Chang Nai-Yuan Nicholas , Dominguez Jessica A. , Farris Alton B. , Buchman Timothy G. , Hunt Clayton R. , Coopersmith Craig M. 
Published: February 2011

AbstractSepsis is primarily a disease of the aged, with increased incidence and mortality occurring in aged hosts. Heat shock protein (HSP) 70 plays an important role in both healthy aging and the stress response to injury. The purpose of this study was to determine the role of HSP70 in mediating mortality and the host inflammatory response in aged septic hosts. Sepsis was induced in both young (6- to 12-wk-old) and aged (16- to 17-mo-old) HSP70−/− and wild-type (WT) mice to determine whether HSP70 modulated outcome in an age-dependent fashion. Young HSP70−/− and WT mice subjected to cecal ligation and puncture, Pseudomonas aeruginosa pneumonia, or Streptococcus pneumoniae pneumonia had no differences in mortality, suggesting HSP70 does not mediate survival in young septic hosts. In contrast, mortality was higher in aged HSP70−/− mice than aged WT mice subjected to cecal ligation and puncture (p = 0.01), suggesting HSP70 mediates mortality in sepsis in an age-dependent fashion. Compared with WT mice, aged septic HSP70−/− mice had increased gut epithelial apoptosis and pulmonary inflammation. In addition, HSP70−/− mice had increased systemic levels of TNF-α, IL-6, IL-10, and IL-1β compared with WT mice. These data demonstrate that HSP70 is a key determinant of mortality in aged, but not young hosts in sepsis. HSP70 may play a protective role in an age-dependent response to sepsis by preventing excessive gut apoptosis and both pulmonary and systemic inflammation.
COMPARISON OF SINE VERSUS PULSE WAVEFORM EFFECTS ON FATIGUE CRACK GROWTH BEHAVIOR OF NR, SBR, AND BR COMPOUNDS
Authors: Andreini G. , Straffi P. , Cotugno S. , Gallone G. , Polacco G. 
Published: February 2011

Abstract
Fatigue crack growth experiments on carbon black-filled rubber compounds have been carried out to evaluate the influence of testing conditions over different compound formulations. Investigations on the influence of waveform, data acquisition, and compound formulation have been performed on strip-tensile specimens reproducing the mode I of crack opening. The response of three different compound formulations (based on either natural rubber, butadiene rubber, or styrene-butadiene rubber) to the application of two different waveforms, pulse and sine, has been analyzed, showing significant differences in fatigue behavior and ranking of the various compounds. Compared to the sinusoidal waveform, the use of a pulse waveform provided an improved correlation of the tearing energy with the crack propagation speed. This difference was particularly evident in the case of natural rubber and butadiene rubber, while it resulted negligible in the case of styrene-butadiene rubber. Such a different behavior could be attributed to differences in macromolecular chains orientation. Fine-tuning of video acquisition parameters provided an accurate observation of the crack growth process, as confirmed by the low standard deviation of the estimated tearing energy and crack growth rate.
Spinodal Decomposition of Blends of Semiconducting and Ferroelectric Polymers
Authors: Asadi Kamal , Wondergem Harry J. , Moghaddam Reza Saberi , McNeill Christopher R. , Stingelin Natalie , Noheda Beatriz , Blom Paul W. M. , de Leeuw Dago M. 
Published: February 2011

AbstractThe operation of resistive switches based on phase‐separated blends of organic ferroelectrics and semiconductors depends significantly on the microstructure of such systems. A wide range of analysis techniques are used to characterize spin‐coated films of the ferroelectric random copolymer poly(vinylidene fluoride‐trifluoroethylene) [P(VDF‐TrFE)], and the semiconducting polymer, regio‐irregular poly(3‐hexylthiophene) (rir‐P3HT). The blend separates into amorphous rir‐P3HT domains embedded in a crystalline P(VDF‐TrFE) matrix. The rir‐P3HT domains are continuous throughout the film, from the substrate/blend interface to the blend/air interface. We also investigate the rir‐P3HT domain size and number as a function of composition and find – unexpectedly – a rather mono‐disperse domain size distribution for a given rir‐P3HT:P(VDF‐TrFE) ratio. The domain size increases with rir‐P3HT content, indicating that the solidification is not dominated by nucleation processes. Spinodal decomposition is therefore more likely to be responsible for the microstructure induced in the rir‐P3HT:P(VDF‐TrFE) blends. Since spinodal decomposition occurs spontaneously without the presence of a nucleation step, this can facilitate processing considerably, since the intricate control of nucleation processes (homogenous or heterogenous) is rendered unnecessary. Measurement of the lateral conductivity of the blends demonstrates that the rir‐P3HT domains are electrically not connected, supporting the microstructural evidence. A perpendicular current through the film is measured using both Au and Ag electrodes as a function of blend composition. A model was used to interpret the electrical transport. The injection for Ag diodes poled into the ON‐state preferentially occurs at the circumference of the rir‐P3HT domains. An accumulation width over which the injection occurs is estimated to be of the order of a few hundred nm.
Errichtung und Zurechnung von Ressortforschungseinrichtungen. Eine Frage des Bedarfs an wissenschaftlicher Expertise?
Authors: Philipps Axel 
Published: February 2011

AbstractThe Constitution and Attribution of Government Research Agencies. A Matter of Need for Science‐generated Policy Knowledge? Government research agencies are a form of extra‐university research institutions. In contrast to other extra‐university research facilities they are subordinate to and financed by respective German governmental departments. As their mission they provide science‐generated information, services, and monitoring to support the governmental departments. In science studies researchers proclaim a rigid association between the installation, attribution, and development of government research agencies and the increasing need for science‐generated policy knowledge. The article examines this assumed association based on the personal, institutional, financial, and mission specific development of government research agencies between the years 1965 and 2005. According to the results the expansion of government research agencies stagnates – like science in general.
Elastic phantoms generated by microfluidics technology: Validation of an imaged‐based approach for accurate measurement of the growth rate of lung nodules
Authors: El‐Baz Ayman , Sethu Palaniappan , Gimel'farb Georgy , Khalifa Fahmi , Elnakib Ahmed , Falk Robert , El‐Ghar Mohamed Abo 
Published: February 2011

AbstractThis paper focuses on validating our approach for monitoring the development of lung nodules detected in successive chest low‐dose computed tomography (LDCT) scans of a patient. Our methodology for monitoring detected lung nodules includes 3D LDCT data registration, which is a non‐rigid technique and involves two steps: (i) global target‐to‐prototype alignment of one scan to another using the experience gained from a prior appearance model, followed by (ii) local alignment to correct for intricate relative deformations. We propose a new approach for validating the accuracy of our algorithm for elastic lung phantoms constructed with state‐of‐the‐art microfluidics technology and in vivo data. Fabricated from a flexible transparent polymer, i.e. polydimethylsiloxane (PDMS), the phantoms mimic the contractions and expansions of the lung and nodules as seen during normal breathing. The in vivo data in our study had been collected from a small control group of four subjects and a larger test group of 27 subjects with known ground truth (biopsy diagnosis. The growth rate and diagnostic results for both phantoms and in vivo data confirm the high accuracy of our algorithm.
Metabolic engineering of Corynebacterium glutamicum for production of 1,5‐diaminopentane from hemicellulose
Authors: Buschke Nele , Schröder Hartwig , Wittmann Christoph 
Published: February 2011

AbstractIn the present work, the bio‐based production of 1,5‐diaminopentane (cadaverine), an important building block for bio‐polyamides, was extended to hemicellulose a non‐food raw material. For this purpose, the metabolism of 1,5‐diaminopentane‐producing Corynebacterium glutamicum was engineered to the use of the C5 sugar xylose. This was realized by heterologous expression of the xylA and xylB genes from Escherichia coli, mediating the conversion of xylose into xylulose 5‐phosphate (an intermediate of the pentose phosphate pathway), in a defined diaminopentane‐producing C. glutamicum strain, recently obtained by systems metabolic engineering. The created mutant, C. glutamicum DAP‐Xyl1, exhibited efficient production of the diamine from xylose and from mixtures of xylose and glucose. Subsequently, the novel strain was tested on industrially relevant hemicellulose fractions, mainly containing xylose and glucose as carbon source. A two‐step process was developed, comprising (i) enzymatic hydrolysis of hemicellulose from dried oat spelts, and (ii) biotechnological 1,5‐diaminopentane production from the obtained hydrolysates with the novel C. glutamicum strain. This now opens a future avenue towards bio‐based 1,5‐diaminopentane and bio‐polyamides thereof from non‐food raw materials.
Atomic layer deposition of titanium dioxide on cellulose acetate for enhanced hemostasis
Authors: Hyde G. Kevin , Stewart S. Michael , Scarel Giovanna , Parsons Gregory N. , Shih Chun‐Che , Shih Chun‐Ming , Lin Shing‐Jong , Su Yea‐Yang , Monteiro‐Riviere Nancy A. , Narayan Roger J. 
Published: February 2011

AbstractTiO2 films may be used to alter the wettability and hemocompatibility of cellulose materials. In this study, pure and stoichiometric TiO2 films were grown using atomic layer deposition on both silicon and cellulose substrates. The films were grown with uniform thicknesses and with a growth rate in agreement with literature results. The TiO2 films were shown to profoundly alter the water contact angle values of cellulose in a manner dependent upon processing characteristics. Higher amounts of protein adsorption indicated by blurry areas on images generated by scanning electron microscopy were noted on TiO2‐coated cellulose acetate than on uncoated cellulose acetate. These results suggest that atomic layer deposition is an appropriate method for improving the biological properties of hemostatic agents and other blood‐contacting biomaterials.
Miniaturized lensless imaging systems for cell and microorganism visualization in point‐of‐care testing
Authors: Gurkan Umut Atakan , Moon Sangjun , Geckil Hikmet , Xu Feng , Wang Shuqi , Lu Tian Jian , Demirci Utkan 
Published: February 2011

AbstractLow‐cost, robust, and user‐friendly diagnostic capabilities at the point‐of‐care (POC) are critical for treating infectious diseases and preventing their spread in developing countries. Recent advances in micro‐ and nanoscale technologies have enabled the merger of optical and fluidic technologies (optofluidics) paving the way for cost‐effective lensless imaging and diagnosis for POC testing in resource‐limited settings. Applications of the emerging lensless imaging technologies include detecting and counting cells of interest, which allows rapid and affordable diagnostic decisions. This review presents the advances in lensless imaging and diagnostic systems, and their potential clinical applications in developing countries. The emerging technologies are reviewed from a POC perspective considering cost effectiveness, portability, sensitivity, throughput and ease of use for resource‐limited settings.
Synthesis, Receptor Binding, and CNS Pharmacological Studies of New Thyrotropin‐Releasing Hormone (TRH) Analogues
Authors: Monga Vikramdeep , Meena Chhuttan L. , Rajput Satyendra , Pawar Chandrashekhar , Sharma Shyam S. , Lu Xinping , Gershengorn Marvin C. , Jain Rahul 
Published: February 2011

AbstractAs part of our search for selective and CNS‐active thyrotropin‐releasing hormone (TRH) analogues, we synthesized a set of 44 new analogues in which His and pGlu residues were modified or replaced. The analogues were evaluated as agonists at TRH‐R1 and TRH‐R2 in cells in vitro, and in vivo in mice for analeptic and anticonvulsant activities. Several analogues bound to TRH‐R1 and TRH‐R2 with good to moderate affinities, and are full agonists at both receptor subtypes. Specifically, analogue 21 a (R=CH3) exhibited binding affinities (Ki values) of 0.17 μM for TRH‐R1 and 0.016 μM for TRH‐R2; it is 10‐fold less potent than TRH in binding to TRH‐R1 and equipotent with TRH in binding to TRH‐R2. Compound 21 a, the most selective agonist, activated TRH‐R2 with a potency (EC50 value) of 0.0021 μM, but activated TRH‐R1 at EC50=0.05 μM, and exhibited 24‐fold selectivity for TRH‐R2 over TRH‐R1. The newly synthesized TRH analogues were also evaluated in vivo to assess their potencies in antagonism of barbiturate‐induced sleeping time, and several analogues displayed potent analeptic activity. Specifically, analogues 21 a,b and 22 a,b decreased sleeping time by nearly 50 % more than TRH. These analogues also displayed potent anticonvulsant activity and provided significant protection against PTZ‐induced seizures, but failed to provide any protection in MES‐induced seizures at 10 μmol kg−1. The results of this study provide evidence that TRH analogues that show selectivity for TRH‐R2 over TRH‐R1 possess potent CNS activity.
Comparison of a Pair of Synthetic Tea‐Catechin‐Derived Epimers: Synthesis, Antifolate Activity, and Tyrosinase‐Mediated Activation in Melanoma
Authors: Sáez‐Ayala Magalí , Sánchez‐del‐Campo Luis , Montenegro María F. , Chazarra Soledad , Tárraga Alberto , Cabezas‐Herrera Juan , Rodríguez‐López José Neptuno 
Published: February 2011

AbstractDespite bioavailability issues, tea catechins have emerged as promising chemopreventive agents because of their efficacy in various animal models. We synthesized two catechin‐derived compounds, 3‐O‐(3,4,5‐trimethoxybenzoyl)‐(−)‐catechin (TMCG) and 3‐O‐(3,4,5‐trimethoxybenzoyl)‐(−)‐epicatechin (TMECG), in an attempt to improve the stability and cellular absorption of tea polyphenols. The antiproliferative and pro‐apoptotic activities of both compounds were analyzed with various cancer cell systems, and TMCG, which was easily synthesized in excellent yield, was more active than TMECG in both melanoma and non‐melanoma cell lines. TMCG was also a better inhibitor of dihydrofolate reductase and was more efficiently oxidized by tyrosinase, potentially explaining the difference in activity between these epimers.
Aurones as Modulators of ABCG2 and ABCB1: Synthesis and Structure–Activity Relationships
Authors: Sim Hong May , Loh Ker Yun , Yeo Wee Kiang , Lee Chong Yew , Go Mei Lin 
Published: February 2011

AbstractThe ability of aurones to modulate the efflux activities of ABCG2 and ABCB1 was investigated by quantifying their effects on the accumulation of pheophorbide A (PhA) in ABCG2‐overexpressing MDA‐MB‐231/R cells and calcein AM in ABCB1‐overexpressing MDCKII/MDR1 cells. Key structural features for interactions at both ABCG2 and ABCB1 are a methoxylated ring A, an intact exocyclic double bond, and the location of the carbonyl bond on ring C. Modifications on rings B and C were less critical and served primarily to moderate activity and selectivity for one or both transporters. These SAR trends were quantified by Free–Wilson analyses and are reflected in a pharmacophore model for PhA accumulation. Several compounds were found to be equipotent with fumitremorgin C (FTC) in promoting PhA accumulation, and they also demonstrated strong affinities for ABCB1. These compounds were disubstituted on ring B with methoxy or a combination of methoxy and hydroxy groups. Taken together, our findings highlight the versatility of the aurone template as a lead scaffold for the design of dual‐targeting ABCG2 and ABCB1 modulators.
Continuous Synthesis of tert‐Butyl Peroxypivalate using a Single‐Channel Microreactor Equipped with Orifices as Emulsification Units
Authors: Illg Tobias , Hessel Volker , Löb Patrick , Schouten Jaap C. 
Published: February 2011

AbstractThe two‐step synthesis of tert‐butyl peroxypivalate is performed in a single‐channel microreactor. The first step, the deprotonation of tert‐butyl hydroperoxide, is done in a simple mixer tube setup. The residence time section for the second reaction step is equipped with orifices for interfacial area renewal, needed for ensuring mass transfer between the two immiscible phases. The strong dependence of the reaction performance on the size of the interfacial area is demonstrated by using a setup with 4 orifices (distance of 52 cm), giving a HPLC yield of 71 % at a residence time of 8 s and a reaction temperature of 23 °C. A further shortening of orifice distances helped to shorten the residence time down to 1.5 s and 0.5 s (using 9 orifices and 3 orifices with a distance of 5 cm). When using these setups, the produced heat could not be removed from the system sufficiently quickly (ΔT=38 K). The achieved yields (ca. 70 % by HPLC) are close to the state of the art (cascaded batch processing) and provide an indication that the tert‐butyl peroxypivalate synthesis can be performed at higher temperatures or at least, a more flexible process control can be allowed compared to high‐volume batch reactors. Processing at higher reaction temperatures up to 70 °C shows a slight optimum at reaction temperatures between 40 °C to 50 °C, depending on the setup used. Knowing this novel process window as well as the optimum orifice geometry and distance will allow for tailored design of the microreactor. For the processing in the single‐channel microreactor setup using 9 orifices (distance of 5 cm) and a reaction temperature of 40 °C a space‐time‐yield of 420 000 g L−1 h−1 was reached which is higher than the space‐time‐yield for the industrial 3 cascaded batch reactor process (190 g L−1 h−1).
Spin Crossover and Solvate Effects in 1D FeII Chain Compounds Containing Bis(dipyridylamine)‐Linked Triazine Ligands
Authors: Ross Tamsyn M. , Moubaraki Boujemaa , Turner David. R. , Halder Gregory J. , Chastanet Guillaume , Neville Suzanne M. , Cashion John D. , Létard Jean‐François , Batten Stuart R. , Murray Keith S. 
Published: February 2011

AbstractA series of 1D polymeric FeII spin crossover (SCO) compounds of type trans‐[FeII(NCX)2(L)]·Solvent has been synthesised {L = DPPyT = 1‐[4,6‐bis(dipyridin‐2‐ylamino)‐1,3,5‐triazin‐2‐yl]pyridin‐4(1H)‐one for 1–4; NCX = NCS– for 1 and 2, NCSe– for 3 and 4; Solvent = 2.5CH2Cl2 for 1, 2CHCl3·0.5CH3OH for 2 and 4, CH2Cl2 for 3; L = DPT (6‐phenoxy‐N2,N2,N4,N4‐tetra‐2‐pyridinyl‐1,3,5‐triazine‐2,4‐diamine) for 5; NCX = NCS– for 5; Solvent = 2CH3OH·H2O for 5; L = DQT {4‐[4,6‐bis(dipyridin‐2‐ylamino)‐1,3,5‐triazin‐2‐yloxy]phenol} for 6–8; NCX– = NCS– for 6; Solvent = 2CH2Cl2 for 6; NCX– = NCSe– for 7; Solvent = CH2Cl2·CH2ClCH2Cl for 7; NCX– = NCSe– for 8; Solvent = 1.5CH2Cl2·0.5CH3OH for 8}. Two mononuclear complexes, trans‐[FeII(NCS)2(DPT)2]·2CH3OH (9) and trans‐[FeII(NCSe)2(DPT)2]·2CH3OH (10), contained the L ligand in a terminal bidentate coordination mode. As well as variations made in the NCX– ligands, variations were also made in substituent groups on the s‐triazine “core” of L to investigate their intermolecular/supramolecular role in crystal packing and, thus, their influence on SCO properties. All the complexes crystallised as solvates, and the influence of the latter on the magnetism and spin transitions was explored. A wide range of physical methods was employed, as a function of temperature, viz. crystallography, PXRD (synchrotron), susceptibilities, LIESST and Mössbauer effect, in order to probe magnetostructural correlations in these 1D families. New examples of half‐crossovers, with ordered –LS–HS–LS–HS– intrachain states existing below T1/2, have been observed and comparisons made to related one‐ or two‐step systems. All the observed transitions are gradual and non‐hysteretic, and brief comments are made in relation to recent theoretical models for cooperativity, developed elsewhere.