bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent biomedical advances with polyampholyte polymers
Authors: Zurick Kevin M. , Bernards Matthew 
Published: October 2013

ABSTRACTPolyampholyte polymer systems are composed of varying mixtures of charged monomer subunits. These polymeric systems have gained increasing attention because it is possible to design the final material properties through careful selection of the charged monomer subunits and controlling the polymer architecture. Characteristics that have been manipulated include the hydration, mechanical properties, pH responsive swelling, temperature responsive swelling, resistance to nonspecific protein adsorption, and protein conjugation capability. This had led researchers to propose the use of polyampholyte polymers as biosensor platforms, fouling release membranes, drug delivery vehicles, and tissue engineering scaffolds. This review is focused on advances that have been made over the last 5 years to develop polyampholyte polymers for these biomedical applications. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 40069.
Fatigue in Ankylosing Spondylitis Is Associated With the Brain Networks of Sensory Salience and Attention
Authors: Wu Qi , Inman Robert D. , Davis Karen D. 
Published: October 2013

ObjectiveFatigue is one of the cardinal features of ankylosing spondylitis (AS) and contributes substantially to the disability associated with this disease. The mechanisms underlying fatigue in AS remain poorly understood, and this has hampered the development of targeted, effective treatment of this disabling feature of AS. The current study was undertaken, therefore, to investigate the brain networks underlying fatigue in AS.MethodsTwenty patients with back pain secondary to AS (15 men and 5 women; mean ± SD age 34.8 ± 11.9 years) and 20 age‐ and sex‐matched controls consented to participate in the study. Patients underwent clinical assessment of AS using the Fatigue Severity Scale, the Affect Intensity Measure, and the McGill Pain Questionnaire. Brain gray matter and white matter connectivity was assessed using 3T magnetic resonance imaging.ResultsThe patients with AS had significant fatigue that correlated with measures of their emotional strength and spinal mobility. Individual fatigue scores were negatively correlated with the amount of gray matter in areas of the dorsal and ventral attention networks, the somatosensory cortices, and the caudate nucleus, but were positively correlated with gray matter within the executive control network and putamen. Moreover, in patients with high fatigue scores, white matter tracts connecting these brain structures (e.g., inferior fronto‐occipital fasciculi, superior/inferior longitudinal fasciculi, and corticothalamic tracts) exhibited low fractional anisotropy (indicative of decreased white matter tract integrity).ConclusionThese data indicate that fatigue in AS involves sensory salience and attention brain networks.
Laquinimod Delays and Suppresses Nephritis in Lupus‐Prone Mice and Affects Both Myeloid and Lymphoid Immune Cells
Authors: Lourenço Elaine V. , Wong Maida , Hahn Bevra H. , Palma‐Diaz M. Fernando , Skaggs Brian J. 
Published: October 2013

ObjectiveLupus nephritis depends on autoantibody deposition and activation of multiple immune cell types that promote kidney inflammation, including lymphocytes and monocyte/macrophages. Laquinimod, currently in clinical trials for multiple sclerosis and lupus nephritis, reduces infiltration of inflammatory cells into the spinal cord in experimental autoimmune encephalomyelitis. Activated monocyte/macrophages infiltrate the kidneys during nephritis in systemic lupus erythematosus (SLE). We undertook this study to determine whether using laquinimod to reduce monocyte/macrophage‐driven tissue damage as well as to alter lymphocytes in SLE nephritis could have greater therapeutic benefit than current treatments that primarily affect lymphocytes, such as mycophenolate mofetil (MMF).MethodsTo test laquinimod efficacy, we used the (NZB × NZW)F1 mouse model of SLE, in which disease manifests as nephritis. Preventive and therapeutic studies were performed to determine whether laquinimod could prevent or delay nephritis, as measured by proteinuria, serum creatinine, survival, and renal pathology. Spleen and kidney leukocyte populations and suppression assays were analyzed by flow cytometry.ResultsLaquinimod prevented or delayed lupus manifestations at levels equal to or better than MMF. Laquinimod treatment was associated with reduced numbers of monocyte/macrophages, dendritic cells, and lymphocytes, as well as with induction of myeloid‐derived suppressor cells in spleens and kidneys. Laquinimod suppressed macrophage‐secreted tumor necrosis factor α and induced production of interleukin‐10 (IL‐10). In addition, laquinimod suppressed interferon‐γ and IL‐17 production by lymphocytes and down‐regulated expression of activation/costimulatory markers on antigen‐presenting cells.ConclusionThe effects of laquinimod on myeloid and lymphoid cells may contribute to improvements in (NZB × NZW)F1 mouse survival, proteinuria, and glomerulonephritis. Future development of laquinimod as a therapeutic agent for lupus nephritis is promising.
Efficacy and Safety of Abatacept in Lupus Nephritis: A Twelve‐Month, Randomized, Double‐Blind Study
Authors: Furie Richard , Nicholls Kathy , Cheng Tien‐Tsai , Houssiau Frederic , Burgos‐Vargas Ruben , Chen Shun‐Le , Hillson Jan L. , Meadows‐Shropshire Stephanie , Kinaszczuk Michael , Merrill Joan T. 
Published: October 2013

ObjectiveTo compare the efficacy and safety of intravenous (IV) abatacept, a selective T cell costimulation modulator, versus placebo for the treatment of active class III or IV lupus nephritis, when used on a background of mycophenolate mofetil and glucocorticoids.MethodsThis was a 12‐month, randomized, phase II/III, multicenter, international, double‐blind study. A total of 298 patients were treated in 1 of 3 IV treatment arms: placebo, abatacept at the standard weight‐tiered dose (approximating 10 mg/kg), or abatacept at 30 mg/kg for 3 months, followed by the standard weight‐tiered dose (abatacept 30/10). The primary end point, time to confirmed complete response, was a composite measure that required maintenance of glomerular filtration rate, minimal proteinuria, and inactive urinary sediment over the 52‐week treatment period.ResultsThere were no differences among treatment arms in the time to confirmed complete response or in the proportion of subjects with confirmed complete response following 52 weeks of treatment. Treatment with abatacept was associated with greater improvements from baseline in anti–double‐stranded DNA antibody, C3, and C4 levels. Among 122 patients with nephrotic‐range proteinuria, treatment with abatacept resulted in an ∼20–30% greater reduction in mean urinary protein‐to‐creatinine ratio compared with placebo. Abatacept was well tolerated; rates of deaths, serious adverse events, and serious infections were similar across treatment arms. Gastroenteritis and herpes zoster occurred more frequently with abatacept treatment.ConclusionAlthough the primary end point was not met, abatacept showed evidence of biologic activity and was well tolerated in patients with active class III or IV lupus nephritis.
Brief Report: Autologous Stem Cell Transplantation Restores Immune Tolerance in Experimental Arthritis by Renewal and Modulation of the Teff Cell Compartment
Authors: Delemarre Eveline M. , Roord Sarah T. A. , van den Broek Theo , Zonneveld‐Huijssoon Evelien , de Jager Wilco , Rozemuller Henk , Martens Anton C. , Broere Femke , Wulffraat Nico M. , Glant Tibor T. , Prakken Berent J. , van Wijk Femke 
Published: October 2013

ObjectiveAutologous stem cell transplantation (ASCT) induces long‐term drug‐free disease remission in patients with juvenile idiopathic arthritis. This study was undertaken to further unravel the immunologic mechanisms underlying ASCT by using a mouse model of proteoglycan‐induced arthritis (PGIA).MethodsFor initiation of PGIA, BALB/c mice received 2 intraperitoneal injections of human PG in a synthetic adjuvant on days 0 and 21. Five weeks after the first immunization, the mice were exposed to total body irradiation (7.5 Gy) and received (un)manipulated bone marrow (BM) grafts from mice with PGIA. Clinical scores, T cell reconstitution, (antigen‐specific) T cell cytokine production, and intracellular cytokine expression were determined following autologous BM transplantation (ABMT).ResultsABMT resulted in amelioration and stabilization of arthritis scores. BM grafts containing T cells and T cell–depleted grafts provided the same clinical benefit, with similar reductions in PG‐induced T cell proliferation and the number of PG‐specific autoantibodies. In vivo reexposure to PG did not exacerbate disease. Following ABMT, basal levels of disease‐associated proinflammatory cytokines (interferon‐γ [IFNγ], interleukin‐17 [IL‐17], and tumor necrosis factor α [TNFα]) were reduced. In addition, restimulation of T cells with PG induced a strong reduction in disease‐associated proinflammatory cytokine production. Finally, although the remaining host T cells displayed a proinflammatory phenotype following ABMT, IFNγ, IL‐17, and TNFα production by the newly reconstituted donor‐derived T cells was significantly lower.ConclusionTaken together, our data suggest that ABMT restores immune tolerance by renewal and modulation of the Teff cell compartment, leading to a strong reduction in proinflammatory (self antigen–specific) T cell cytokine production.
Relationship between chain collapse and secondary structure formation in a partially folded protein
Authors: Nakagawa Kanako , Yamada Yoshiteru , Matsumura Yoshitaka , Tsukamoto Seiichi , Yamamoto‐Ohtomo Mio , Ohtomo Hideaki , Okabe Takahiro , Fujiwara Kazuo , Ikeguchi Masamichi 
Published: October 2013

ABSTRACTChain collapse and secondary structure formation are frequently observed during the early stages of protein folding. Is the chain collapse brought about by interactions between secondary structure units or is it due to polymer behavior in a poor solvent (coil‐globule transition)? To answer this question, we measured small‐angle X‐ray scattering for a series of β‐lactoglobulin mutants under conditions in which they assume a partially folded state analogous to the folding intermediates. Mutants that were designed to disrupt the secondary structure units showed the gyration radii similar to that of the wild type protein, indicating that chain collapse is due to coil‐globule transitions. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 651–658, 2014.
Age‐related differences in auditory evoked potentials as a function of task modulation during speech–nonspeech processing
Authors: Rufener Katharina Simone , Liem Franziskus , Meyer Martin 
Published: October 2013

AbstractBackgroundHealthy aging is typically associated with impairment in various cognitive abilities such as memory, selective attention or executive functions. Less well observed is the fact that also language functions in general and speech processing in particular seems to be affected by age. This impairment is partly caused by pathologies of the peripheral auditory nervous system and central auditory decline and in some part also by a cognitive decay.AimsThis cross‐sectional electroencephalography (EEG) study investigates temporally early electrophysiological correlates of auditory related selective attention in young (20–32 years) and older (60–74 years) healthy adults.Material and methodsIn two independent tasks, we systematically modulate the subjects' focus of attention by presenting words and pseudowords as targets and white noise stimuli as distractors.ResultsBehavioral data showed no difference in task accuracy between the two age samples irrespective of the modulation of attention. However, our work is the first to show that the N1‐ and the P2 component evoked by speech and nonspeech stimuli are specifically modulated in older adults and young adults depending on the subjects' focus of attention.ConclusionThis finding is particularly interesting in that the age‐related differences in AEPs may be reflecting levels of processing that are not mirrored by the behavioral measurements.
BRD4 associates with p53 in DNMT3A‐mutated leukemia cells and is implicated in apoptosis by the bromodomain inhibitor JQ1
Authors: Stewart Helen Jayne Susan , Horne Gillian Abigail , Bastow Sarah , Chevassut Timothy James Telfer 
Published: October 2013

AbstractThe bromodomain and extra terminal (BET) family protein bromodomain containing protein 4 (BRD4) is an epigenetic regulator recently identified as a therapeutic target for several hematological cancers, notably mixed lineage leukemia‐fusion acute myeloid leukemia (MLL‐AML). Here, we show that the BRD4 bromodomain inhibitor JQ1 is highly active against the p53‐wild‐type Ontario Cancer Institute (OCI)‐AML3 cell line which carries mutations in nucleophosmin (NPM1) and DNA methyltransferase 3 (DNMT3A) genes commonly associated with poor prognostic disease. We find that JQ1 causes caspase 3/7‐mediated apoptosis and DNA damage response in these cells. In combination studies, we show that histone deacetylase (HDAC) inhibitors, the HDM2 inhibitor Nutlin‐3, and the anthracycline daunorubicin all enhance the apoptotic response of JQ1. These compounds all induce activation of p53 suggesting that JQ1 might sensitize AML cells to p53‐mediated cell death. In further experiments, we show that BRD4 associates with acetylated p53 but that this association is not inhibited by JQ1 indicating that the protein–protein interaction does not involve bromodomain binding of acetylated lysines. Instead, we propose that JQ1 acts to prevent BRD4‐mediated recruitment of p53 to chromatin targets following its activation in OCI‐AML3 cells resulting in cell cycle arrest and apoptosis in a c‐MYC‐independent manner. Our data suggest that BET bromodomain inhibition might enhance current chemotherapy strategies in AML, notably in poor‐risk DNMT3A/NPM1‐mutated disease.
Strain‐Promoted Azide–Alkyne Cycloaddition with Ruthenium(II)–Azido Complexes
Authors: Cruchter Thomas , Harms Klaus , Meggers Eric 
Published: October 2013

AbstractThe reactivity of an exemplary ruthenium(II)–azido complex towards non‐activated, electron‐deficient, and towards strain‐activated alkynes at room temperature and low millimolar azide and alkyne concentrations has been investigated. Non‐activated terminal and internal alkynes failed to react under such conditions, even under copper(I) catalysis conditions. In contrast, as expected, rapid cycloaddition was observed with electron‐deficient dimethyl acetylenedicarboxylate (DMAD) as the dipolarophile. Since DMAD and related propargylic esters are excellent Michael acceptors and thus unsuitable for biological applications, we investigated the reactivity of the azido complex towards cycloaddition with derivatives of cyclooctyne (OCT), bicyclo[6.1.0]non‐4‐yne (BCN), and azadibenzocyclooctyne (ADIBO). While no reaction could be observed in the case of the less strained cyclooctyne OCT, the highly strained cyclooctynes BCN and ADIBO readily reacted with the azido complex, providing the corresponding stable triazolato complexes, which were amenable to purification by conventional silica gel column chromatography. An X‐ray crystal structure of an ADIBO cycloadduct was obtained and verified that the formed 1,2,3‐triazolato ligand coordinates the metal center through the central N2 atom. Importantly, the determined second‐order rate constant for the ADIBO cycloaddition with the azido complex (k2=6.9 × 10−2 M−1 s−1) is comparable to the rate determined for the ADIBO cycloaddition with organic benzyl azide (k2=4.0 × 10−1 M−1 s−1). Our results demonstrate that it is possible to transfer the concept of strain‐promoted azide–alkyne cycloaddition (SPAAC) from purely organic azides to metal‐coordinated azido ligands. The favorable reaction kinetics for the ADIBO‐azido‐ligand cycloaddition and the well‐proven bioorthogonality of strain‐activated alkynes should pave the way for applications in living biological systems.
Functionalized Polymer‐Based Spherical Activated Carbon for Liquid and Gas Phase Applications
Authors: Schrage Christian , Modrow Antje , Fichtner Sven , Giebelhausen Jann Michael , Böhringer Bertram 
Published: October 2013

AbstractPolymerbasierte sphärische Aktivkohle (PBSAK) kann durch die Integration von reaktiven Komponenten in das Porensystem funktionalisiert werden. Dadurch erschließen sich neue Anwendungsbereiche für diese Adsorbentien. So kann imprägnierte PBSAK als Breitbandsorbens für Atemschutzanwendungen und zur Entfernung von Metallen aus belastetem Wasser eingesetzt werden, während stickstofffunktionalisierte PBSAK für die Reinigung von Gasströmen gut geeignet ist. Außerdem können oberflächenmodifizierte PBSAK zur Gewinnung von Wertstoffen wie Gold oder Uran eingesetzt werden.
Kinetic Separation of Methane Containing Gas Mixtures via Carbon Molecular Sieves
Authors: Möller Andreas , Guderian Joachim , Möllmer Jens , Lange Marcus , Hofmann Jörg , Gläser Roger 
Published: October 2013

AbstractDie Erzeugung von Biomethan in Erdgasqualität aus methanhaltigen Gasgemischen ist ein wichtiger Beitrag im Rahmen der Nutzung erneuerbarer Energien. Hierzu können thermische Trennverfahren wie Gaswäschen, Adsorptions‐ und Membrantrennverfahren eingesetzt werden. Bei Verwendung des Adsorptionsverfahrens werden die Hauptkomponenten Methan und Kohlendioxid unter Ausnutzung des kinetischen Effektes an Kohlenstoffmolekularsieben separiert. Hierbei adsorbiert CO2 an der inneren Oberfläche der Kohlenstoffmolekularsiebe, während CH4 aufgrund der sehr langsamen Kinetik in der Gasphase verbleibt. Für die Bewertung der Materialien und der Effektivität des Gesamtprozesses müssen sowohl die Gleichgewichtsbeladungen als auch die kinetischen Kenngrößen bekannt sein.
Effects of metoprolol on heart rate in patients with digitalis treated chronic atrial fibrillation
Authors: Khalsa A. , Edvardsson N. , Olsson S. B. 
Published: October 2013

AbstractAdequate control of ventricular rate in patients with chronic atrial fibrillation (AF) may not be achieved with digitalis alone. In the present study the additional effect of two different doses (50 mg and 50 + 50 mg) of oral metoprolol, a new selective β‐blocking agent, on ventricular rate in patients with longstanding AF has been studied. A decrease in the mean ventricular rate during rest and during exercise at various work loads was observed after both doses. The effect was more pronounced at the highest work load of 80 W, both after 50 mg (p < 0.002) and after 50 + 50 mg (p < 0.01) of the drug. A high initial heart rate at rest or during exercise was reduced more by the drug than a lower one. Exercise tolerance was reduced in 2 patients. These results suggest that patients with AF in whom satisfactory control of heart rate cannot be achieved with digitalis alone may benefit from addition of individualized metoprolol therapy.
Evaluation of sinus node automaticity and sinoatrial conduction in children with normal and abnormal sinus node function
Authors: Yabek S. M. 
Published: October 2013

AbstractSinus node recovery time (SNRT) and sinoatrial conduction time (SACT) were determined in each of 28 children. Eighteen children (ages 2 to 14 years) had electrocardiographically normal sinus node function and served as controls. Ten children (ages 4 to 13 years) had electrocardiographic evidence of sinus node dysfunction, consisting of inappropriate sinus bradycardia, periods of sinus arrest or sinoatrial exit block. Mean control SNRT was 133% of the sinus cycle length with an upper normal limit of 151% (mean + 2 SD). Control SACTs ranged from 45‐105 ms with mean and mean + 2 SD values of 71 ms und 105 ms.In the patients with SND, SNRTs averaged 168% and five patients had abnormally prolonged values of 158 to 256%. Mean SACT was 101 ms with four children having values greater than 105 ms. Seven of the 10 patients with SND had at least one electrophysiologic abnormality.This study defines normal sinoatrial conduction in children and validates the data by demonstrating a close correlation with similar data obtained from adult populations. Although abnormal electrophysiologic data confirms the presence of sinus node dysfunction, normal values for SNRT and SACT do not insure normal sinus node function.
Angiographic restudy of coronary artery bypass grafts simplified by a marker
Authors: Halseth W. L. , Elliott D. P. , Walker E. L. , Meza F. 
Published: October 2013

AbstractThis study was done to examine the benefit of utilizing a stainless steel circumferential aorta‐saphenous vein anastomosis marker.Cardiac catheterization was performed in 87 patients following coronary artery bypass surgery. The exact aorta saphenous anastomotic site was quickly identified and successfully injected in 100% of the patients. During operation stainless steel circumferential markers were placed around the anastomotic site in 1,061 consecutive patients with 3,367 grafts. There was no early or late morbidity or complication from the circumferential markers.
Significance of the negative exercise test in evaluation of patients with chest pain
Authors: Weisburst M. R. , Most A. S. , Williams D. O. 
Published: October 2013

AbstractFifty‐three patients with chest pain and a negative exercise test at greater than 85% predicted maximal heart rate underwent coronary arteriography. Twenty‐one patients (40%) had significant luminal narrowing in one or two vessels. No patient had left main disease. Pathologic electrocardiographic Q waves were present in only coronary heart disease patients (p < 0.001). There was no difference (p > 0.05) in prevalence of T wave abnormalities, chest pain or ventricular beats during exercise in patients with or without coronary disease. Analysis of sex distribution revealed that typical angina pectoris was uncommon in the women (p < 0.001) and all twenty‐one coronary patients were men (p < 0.001). We conclude that in patients with chest pain and a negative exercise test, three vessel or left main coronary artery disease is unlikely. Also, women with atypical chest pain and a negative exercise test are unlikely to have a fixed coronary obstruction.
Prodromal characteristics as indicators of cardiac events in patients hospitalized for chest pain
Authors: Schroeder J. S. , Lamb I. H. , Hu M. 
Published: October 2013

AbstractIn an effort to determine the usefulness of prodromata for predicting a myocardial infarction, a prospective analysis was made of 211 consecutive patients with chest pain who were admitted to the Stanford University Medical Center Coronary Care Unit. In their subsequent course, 91 patients had a myocardial infarction, 102 had a myocardial infarction ruled‐out, and 18 had a noncardiac etiology for their chest pain. Prodromal chest pain in the previous six months had occurred in 65% of patients and unstable angina in 61%. Infarction versus noninfarction patient groups could not be identified on the basis of prodromal ill health, chest pain, unstable angina, typical versus atypical nature of the chest pain, or activity at the onset of pain. Complaints of preceding fatigue and increased perceived stress were common in both groups. Activity at the onset of the admission chest pain was strenuous in 15% of the infarction patients and 12% of the noninfarction patients. We conclude that prodromal symptoms are common in both infarction and noninfarction patients. Although chest pain probably remains the single most frequent identifier of a new cardiac event, it is common in noninfarction patients and cannot be used alone to predict infarction or death.