bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ubiquitin proteasome system and efficacy of proteasome inhibitors in diseases
Authors: Chitra Selvarajan , Nalini Ganesan , Rajasekhar Gopalakrishnan 
Published: May 2012

AbstractIn eukaryotes the ubiquitin proteasome pathway plays an important role in cellular homeostasis and also it exerts a critical role in regulating a wide variety of cellular pathways, including cell growth and proliferation, apoptosis, DNA repair, transcription and immune response. Defects in these pathways have been implicated in a number of human pathologies. Inhibition of the ubiquitin proteasome pathway by proteasome inhibitors may be a rational therapeutic approach for various diseases, such as cancer and inflammatory diseases. Many of the critical cytokine and chemokine mediators of the progression of rheumatoid arthritis are regulated by nuclear factor kappa B (NF‐κB). In peptidoglycan/polysaccharide‐induced polyarthritis, proteasome inhibitors limit the overall inflammation, reduce NF‐κB activation, decrease cellular adhesion molecule expression, inhibit nitric oxide synthase, attenuate circulating levels of proinflammatory cytokine interleukin‐6 and reduce the arthritis index and swelling in the joints of the animals. Since proteasome inhibitors exhibit anti‐inflammatory and anti proliferative effects, diseases characterized by both of these processes such as rheumatoid arthritis might also represent clinical opportunities for such drugs. The regulation of the proteasomal complex by proteasome inhibitors also has implications and potential benefits for the treatment of rheumatoid arthritis. This review summarizes the ubiquitin proteasome pathway, the structure of 26S proteasomes and types of proteasome inhibitors, with their actions, and clinical applications of proteasome inhibitors in various diseases.
Oral Histories in Meteoritics and Planetary Science – XVII: Joseph Goldstein
Authors: SEARS Derek W. G. 
Published: May 2012

Abstract– In this interview, Joseph Goldstein (Fig. 1) recounts how he became interested in meteorites during his graduate studies working with Robert Ogilvie at MIT. By matching the Ni profiles observed across taenite fields in the Widmanstätten structure of iron meteorites with profiles he computed numerically he was able to determine cooling rates as the meteorites cooled through 650–400 °C. Upon graduating, he worked with a team of meteorite researchers led by Lou Walter at Goddard Space Flight Center where for 4 years he attempted to understand metallographic structures by reproducing them in the laboratory. Preferring an academic environment, Joe accepted a faculty position in the rapidly expanding metallurgy department at Lehigh University where he was responsible for their new electron microprobe. He soon became involved in studying the metal from lunar soils and identifying the metallic component from its characteristic iron and nickel compositions. Over the next two decades he refined these studies of Ni diffusion in iron meteorites, particularly the effect of phosphorus in the process, which resulted in superior Fe‐Ni‐P phase diagrams and improved cooling rates for the iron meteorites. After a period as vice president for research at Lehigh, in 1993 he moved to the University of Massachusetts to serve as dean of engineering, but during these administrative appointments Joe produced a steady stream of scientific results. Joe has served as Councilor, Treasurer, Vice President, and President of the Meteoritical Society. He received the Leonard Medal in 2005, the Sorby Award in 1999, and the Dumcumb Award for in 2008. Joseph Goldstein.image
Prevalence of oral mucosal lesions in adults undergoing highly active antiretroviral therapy in Hong Kong
Authors: Perera Mahendra , Tsang Peter Chiu Shun , Samaranayake Lakshman , Lee Man Po , Li Patrick 
Published: May 2012

AbstractAim: Highly active antiretroviral therapy (HAART) has altered the prevalence and incidence of oral mucosal lesions of HIV infection. Recent reports show a variation in the prevalence of oral mucosal lesions in different population groups. Understanding the prevalence of these lesions is of paramount importance in the efficient delivery of dental care to such cohorts. The aim of the present study was to investigate the prevalence of oral mucosal lesions and salivary parameters during HAART in an ethnic Chinese cohort in Hong Kong.Methods:  A cross‐sectional estimation of the prevalence of oral mucosal lesions was carried out in 101 HIV‐infected ethnic Chinese in Hong Kong using the European Community–Clearinghouse classification.Results:  The prevalence of oral mucosal lesions was more common in patients who were classified at baseline as Centers for Disease Control (CDC) C3 category than CDC A2, A3, B2, and B3 (P < 0.05). An overall prevalence of 1.98% was observed for oral Kaposi’s sarcoma. Additionally, the HIV group on HAART (0.37 ± 0.23 mL/min) had significantly lower salivary flow rates (P < 0.01) compared with the healthy group (0.49 ± 0.15 mL/min).Conclusions:  Although HAART appears to markedly reduce the prevalence of oral mucosal lesions during the course of HIV disease, regular systematic oral screening is still warranted for such populations for the early diagnosis and management of pathologies, such as Kaposi’s sarcoma.
Simapse – simulation maps for ecological niche modelling
Authors: Tarroso Pedro , Carvalho Sílvia B. , Brito José Carlos 
Published: May 2012

Summary1. Artificial neural networks (ANNs) are known for their powerful predictive power in the analysis of both linear and nonlinear relationships. They have been successfully applied to several fields including ecological modelling and predictive species’ distributions.2. Here we present Simapse – Simulation Maps for Ecological Niche Modelling, a free and open‐source application written in Python and available to the most common platforms. It uses ANNs with back‐propagation to build spatially explicit distribution models from species data (presence/absence, presence‐only and abundance).3. The main features include the automatic production of replicates with different sub‐sampling methods and total control of ANN structure and learning parameters.4. Simapse uses common text formats as main input and output and provides assessment of variable importance and behaviour and measurement of model fitness.
Characterising surface energy of pharmaceutical powders by inverse gas chromatography at finite dilution
Authors: Das Shyamal C , Stewart Peter J 
Published: May 2012

Abstract

Objectives
The objectives of this project were the use of surface energy distributions in: distinguishing the effects of magnesium stearate on the surface energy of lactose processed by two methods: mixing in a Turbula and mechanofusion; characterising surface energy of materials before and after micronisation; and understanding surface energy changes of micronised lactose before and after storage at high relative humidity (RH).

Methods
Heptane, octane and nonane were used to determine nonpolar surface energy, and dichloromethane and ethyl acetate were used to determine polar surface energy in inverse gas chromatography at finite dilution.

Key findings
The total surface energy of lactose decreased more after mechanofusion with magnesium stearate than mixing in Turbula. The nonpolar surface energy of indometacin increased while polar and total surface energies decreased after micronisation. The nonpolar, polar and total surface energies and work of cohesion of micronised lactose decreased after storage at 75%RH for three months.

Conclusions
The surface energy distributions determined at finite dilution successfully distinguished and revealed more information than infinite dilution on surface energy changes in materials undergoing different pharmaceutical processes such as mixing, mechanofusion, micronisation and storage at high RH.
Osteocalcin is independently associated with body mass index in adolescent girls
Authors: Dubnov‐Raz G. , Ish‐Shalom S. , Chodick G. , Rozen G. S. , Giladi A. , Constantini N. W. 
Published: May 2012

SummaryObjectiveOsteocalcin is a bone‐related protein, recently found to correlate with body mass index (BMI), waist circumference, fat percentage and metabolic syndrome in adults. The aim of this study was to determine the relationship between osteocalcin and BMI in adolescence, a time of significant bone accrual, while considering possible confounders related to bone and body composition.MethodsWe analyzed data from 160 female adolescents (mean age 15.1 ± 0.7 years), which were divided into tertiles by osteocalcin levels. Across these three groups, we examined the differences in BMI with relation to age, total daily energy intake, calcium intake, physical activity (PA), total body bone mineral density, parathyroid hormone (PTH), 25(OH)‐vitamin D, bone alkaline phosphatase and body fat percentage.ResultsMean BMI values differed significantly between participants in the three osteocalcin tertiles, including after adjustment for age, PA, PTH, energy and calcium intakes. Post‐hoc analysis revealed that girls in the highest osteocalcin tertile, had a significantly lower BMI than those in the two lower ones (19.3 ± 2.2 vs. 20.6 ± 3.0 and 20.7 ± 2.9 kg m−2, respectively, P = 0.018). There was no significant difference in energy and calcium intakes, bone mineral density, 25(OH)‐vitamin D levels and PTH between study groups.ConclusionsIn female adolescents, BMI is inversely related to osteocalcin, even after consideration of several factors that may affect bone and fat mass. As bone mineral density, 25(OH)D and PTH did not differ between groups, it is possible that the relation between osteocalcin and BMI could be unrelated to bone tissue itself.
Ultrasound‐guided identification of cardiac imaging windows
Authors: Liu Garry , Qi Xiu‐Ling , Robert Normand , Dick Alexander J. , Wright Graham A. 
Published: May 2012

Purpose:Currently, the use of cine magnetic resonance imaging (MRI) to identify cardiac quiescent periods relative to the electrocardiogram (ECG) signal is insufficient for producing submillimeter‐resolution coronary MR angiography (MRA) images. In this work, the authors perform a time series comparison between tissue Doppler echocardiograms of the interventricular septum (IVS) and concurrent biplane x‐ray angiograms. Our results indicate very close agreement between the diastasis gating windows identified by both the IVS and x‐ray techniques.Methods:Seven cath lab patients undergoing diagnostic angiograms were simultaneously scanned during a breath hold by ultrasound and biplane x‐ray for six to eight heartbeats. The heart rate of each patient was stable. Dye was injected into either the left or right‐coronary vasculature. The IVS was imaged using color tissue Doppler in an apical four‐chamber view. Diastasis was estimated on the IVS velocity curve. On the biplane angiograms, proximal, mid, and distal regions were identified on the coronary artery (CA). Frame by frame correlation was used to derive displacement, and then velocity, for each region. The quiescent periods for a CA and its subsegments were estimated based on velocity. Using Pearson's correlation coefficient and Bland–Altman analysis, the authors compared the start and end times of the diastasis windows as estimated from the IVS and CA velocities. The authors also estimated the vessel blur across the diastasis windows of multiple sequential heartbeats of each patient.Results:In total, 17 heartbeats were analyzed. The range of heart rate observed across patients was 47–79 beats per minute (bpm) with a mean of 57 bpm. Significant correlations (R > 0.99; p < 0.01) were observed between the IVS and x‐ray techniques for the identification of the start and end times of diastasis windows. The mean difference in the starting times between IVS and CA quiescent windows was −12.0 ms. The mean difference in end times between IVS and CA quiescent windows was −3.5 ms. In contrast, the correlation between RR interval and both the start and duration of the x‐ray gating windows were relatively weaker: R = 0.63 (p = 0.13) and R = 0.86 (p = 0.01). For IVS gating windows, the average estimated vessel blurs during single and multiple heartbeats were 0.5 and 0.66 mm, respectively. For x‐ray gating windows, the corresponding values were 0.26 and 0.44 mm, respectively.Conclusions:In this study, the authors showed that IVS velocity can be used to identify periods of diastasis for coronary arteries. Despite variability in mid‐diastolic rest positions over multiple steady rate heartbeats, vessel blurring of 0.5–1 mm was found to be achievable using the IVS gating technique. The authors envision this leading to a new cardiac gating system that, compared with conventional ECG gating, provides better resolution and shorter scan times for coronary MRA.
High Titer and Avidity of Nonneutralizing Antibodies against Influenza Vaccine Antigen Are Associated with Severe Influenza
Authors: To Kelvin K. W. , Zhang Anna J. X. , Hung Ivan F. N. , Xu Ting , Ip Whitney C. T. , Wong Rebecca T. Y. , Ng Joseph C. K. , Chan Jasper F. W. , Chan Kwok-Hung , Yuen Kwok-Yung 
Published: May 2012

ABSTRACTThe importance of neutralizing antibody in protection against influenza virus is well established, but the role of the early antibody response during the initial stage of infection in affecting the severity of disease is unknown. The 2009 influenza pandemic provided a unique opportunity for study because most patients lacked preexisting neutralizing antibody. In this study, we compared the antibody responses of 52 patients with severe or mild disease, using sera collected at admission. A microneutralization (MN) assay was used to detect neutralizing antibody. We also developed an enzyme-linked immunosorbent assay (ELISA) which detects both neutralizing and nonneutralizing antibodies against viral antigens from a split-virion inactivated monovalent influenza virus vaccine. While the MN titers were not significantly different between the two groups (P= 0.764), the ELISA titer and ELISA/MN titer ratio were significantly higher for patients with severe disease than for those with mild disease (P= 0.004 andP= 0.011, respectively). This finding suggested that in patients with severe disease, a larger proportion of serum antibodies were antibodies with no detectable neutralizing activity. The antibody avidity was also significantly higher in patients with severe disease than in those with mild disease (P< 0.05). Among patients with severe disease, those who required positive pressure ventilation (PPV) had significantly higher ELISA titers than those who did not require PPV (P< 0.05). Multivariate analysis showed that the ELISA titer and antibody avidity were independently associated with severe disease. Higher titers of nonneutralizing antibody with higher avidity at the early stage of influenza virus infection may be associated with worse clinical severity and poorer outcomes.
Immunobiotic Lactobacillus jensenii Modulates the Toll-Like Receptor 4-Induced Inflammatory Response via Negative Regulation in Porcine Antigen-Presenting Cells
Authors: Villena Julio , Suzuki Rie , Fujie Hitomi , Chiba Eriko , Takahashi Takuya , Tomosada Yohsuke , Shimazu Tomoyuki , Aso Hisashi , Ohwada Shyuichi , Suda Yoshihito , Ikegami Shuji , Itoh Hiroyuki , Alvarez Susana , Saito Tadao , Kitazawa Haruki 
Published: May 2012

ABSTRACTPreviously, we demonstrated thatLactobacillus jenseniiTL2937 attenuates the inflammatory response triggered by activation of Toll-like receptor 4 (TLR-4) in porcine intestinal epithelial cells. In view of the critical importance of antigen-presenting cell (APC) polarization in immunoregulation, the objective of the present study was to examine the effect of strain TL2937 on the activation patterns of APCs from swine Peyer's patches (PPs). We demonstrated that direct exposure of porcine APCs toL. jenseniiin the absence of inflammatory signals increased expression of interleukin-10 (IL-10) and transforming growth factor β in CD172a+APCs and caused them to display tolerogenic properties. In addition, pretreatment of CD172a+APCs withL. jenseniiresulted in differential modulation of the production of pro- and anti-inflammatory cytokines in response to TLR4 activation. The immunomodulatory effect of strain TL2937 was not related to a downregulation of TLR4 but was related to an upregulation of the expression of three negative regulators of TLRs: single immunoglobulin IL-1-related receptor (SIGIRR), A20, and interleukin-1 receptor-associated kinase M (IRAK-M). Our results also indicated that TLR2 has an important role in the anti-inflammatory activity ofL. jenseniiTL2937, since anti-TLR2 antibodies blocked the upregulation of SIGIRR and IRAK-M in CD172a+APCs and the production of IL-10 in response to TLR4 activation. We performed, for the first time, a precise functional characterization of porcine APCs from PPs, and we demonstrated that CD172a+cells were tolerogenic. Our findings demonstrate that adherent cells and isolated CD172a+cells harvested from swine PPs were useful forin vitrostudy of the inflammatory responses in the porcine gut and the immunomodulatory effects of immunobiotic microorganisms.
Optimizing Outpatient Serial Sputum Colony Counting for Studies of Tuberculosis Treatment in Resource-Poor Settings
Authors: Sloan Derek J. , Corbett Elizabeth L. , Butterworth Anthony E. , Mwandumba Henry C. , Khoo Saye H. , Mdolo Aaron , Shani Doris , Kamdolozi Mercy , Allen Jenny , Mitchison Denis A. , Coleman David J. , Davies Geraint R. 
Published: May 2012

ABSTRACT

Serial Sputum Colony Counting (SSCC) is an important technique in clinical trials of new treatments for tuberculosis (TB). Quantitative cultures on selective Middlebrook agar are used to calculate the rate of bacillary elimination from sputum collected from patients at different time points during the first 2 months of therapy. However, the procedure can be complicated by high sample contamination rates. This study, conducted in a resource-poor setting in Malawi, assessed the ability of different antifungal drugs in selective agar to reduce contamination. Overall, 229 samples were studied and 15% to 27% were contaminated. Fungal organisms were particularly implicated, and samples collected later in treatment were at particular risk (
P
< 0.001). Amphotericin B (AmB) is the standard antifungal drug used on SSCC plates at a concentration of 10 mg/ml. On selective Middlebrook 7H10 plates, AmB at 30 mg/ml reduced sample contamination by 17% compared with AmB at 10 mg/ml. The relative risk of contamination using AmB at 10 mg/ml was 1.79 (95% confidence interval [CI], 1.25 to 3.55). On Middlebrook 7H11 plates, a combination of AmB at 10 mg/ml and carbendazim at 50 mg/ml was associated with 10% less contamination than AmB at 30 mg/ml. The relative risk of contamination with AmB at 30 mg/ml was 1.79 (95% CI, 1.01 to 3.17). Improved antifungal activity was accompanied by a small reduction in bacillary counts, but this did not affect modeling of bacillary elimination. In conclusion, a combination of AmB and carbendazim optimized the antifungal activity of selective media for growth of TB. We recommend this method to reduce contamination rates and improve SSCC studies in African countries where the burden of TB is highest.
First Report of Spontaneous Intrapartum Atopobium vaginae Bacteremia
Authors: Chan Jasper F. W. , Lau Susanna K. P. , Curreem Shirly O. T. , To Kelvin K. W. , Leung Sally S. M. , Cheng Vincent C. C. , Yuen Kwok-Yung , Woo Patrick C. Y. 
Published: May 2012

ABSTRACT

We report the first case of spontaneous intrapartum
Atopobium vaginae
bacteremia identified by 16S rRNA gene sequencing. The bacterium was misidentified by RapID ANA II, API Rapid ID 32A, and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). The likely source of bacteremia was the female genital tract. In invasive infections caused by
A. vaginae
, β-lactams and clindamycin are the antibiotics of choice, as most strains are resistant to metronidazole.
Resistance to Voriconazole Due to a G448S Substitution in Aspergillus fumigatus in a Patient with Cerebral Aspergillosis
Authors: Pelaez Teresa , Gijón Paloma , Bunsow Eleonora , Bouza Emilio , Sánchez-Yebra Waldo , Valerio Maricela , Gama Beatriz , Cuenca-Estrella Manuel , Mellado Emilia 
Published: May 2012

ABSTRACT

A voriconazole-resistant isolate of
Aspergillus fumigatus
was recovered from an immunocompetent patient receiving long-term antifungal therapy for cerebral aspergillosis. A G448S amino acid substitution in the azole target (Cyp51A) was identified as the cause of the resistance phenotype. This article describes the first isolation of a voriconazole-resistant
A. fumigatus
isolate from an immunocompetent patient in Spain.
Identification of Bacterial Pathogens in Ascitic Fluids from Patients with Suspected Spontaneous Bacterial Peritonitis by Use of Broad-Range PCR (16S PCR) Coupled with High-Resolution Melt Analysis
Authors: Hardick Justin , Won Helen , Jeng Kevin , Hsieh Yu-Hsiang , Gaydos Charlotte A. , Rothman Richard E. , Yang Samuel 
Published: May 2012

ABSTRACT
Spontaneous bacterial peritonitis (SBP) can be a severe complication occurring in patients with cirrhosis and ascites, with associated mortality often as high as 40%. Traditional diagnostics for SBP rely on culture techniques for proper diagnosis, although recent reports suggest that the presence of bacterial DNA in peritoneal fluid in patients with cirrhosis and ascites is an indicator of SBP. A previously published broad-range PCR (16S PCR) coupled with high-resolution melt analysis (HRMA) was compared with standard culture techniques for diagnosis of SBP in 106 peritoneal fluid samples from patients with suspected SBP. The sensitivity and specificity for 16S PCR for detecting eubacterial DNA compared with those of standard culture techniques were 100% (17/17) and 91.5% (85/89), respectively. Overall, HRMA concordance with species identification was 70.6% (12/17), although the 5 samples that were discordant at the species level were SBP resulting from a polymicrobial infection, and species-level identification for polymicrobial infections is outside the capability of HRMA. Both the broad-range 16S PCR and HRMA analysis provide useful diagnostic adjunctive assays for clinicians in detecting and identifying pathogens responsible for SBP.
Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry-Based Method for Discrimination between Molecular Types of Cryptococcus neoformans and Cryptococcus gattii
Authors: Posteraro Brunella , Vella Antonietta , Cogliati Massimo , De Carolis Elena , Florio Ada Rita , Posteraro Patrizia , Sanguinetti Maurizio , Tortorano Anna Maria 
Published: May 2012

ABSTRACT

We evaluated the usefulness of matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) for
Cryptococcus
identification at the species and subspecies levels by using an in-house database of 25 reference cryptococcal spectra. Eighty-one out of the 82
Cryptococcus
isolates (72
Cryptococcus neoformans
and 10
Cryptococcus gattii
) tested were correctly identified with respect to their molecular type designations. We showed that MALDI-TOF MS is a practicable alternative to conventional mycology or DNA-based methods.
Promise versus Reality: Optimism Bias in Package Inserts for Tuberculosis Diagnostics
Authors: Denkinger Claudia M. , Grenier Jasmine , Minion Jessica , Pai Madhukar 
Published: May 2012

ABSTRACT
Laboratorians and clinicians often rely on package inserts of diagnostic tests to assess their accuracy. We compared test accuracy for tuberculosis diagnostics reported in 19 package inserts against estimates in published meta-analyses and found that package inserts generally report overoptimistic accuracy estimates. However, package inserts of most tests approved by the U.S. Food and Drug Administration (FDA) or endorsed by the World Health Organization provide more realistic estimates that agree with meta-analyses.