bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of sterility testing of cord blood: challenges and results
Authors: Ramirez‐Arcos Sandra , Kou Yuntong , Yang Lin , Perkins Heather , Taha Mariam , Halpenny Mike , Elmoazzen Heidi
Published: March 2015

BACKGROUND

Sterility testing for cord blood (CB) products is mandatory to prevent transplantation‐transmitted microbial infections. Here, the automated BacT/ALERT (bioMérieux) culture system was validated to detect microbial contamination in CB units processed at the Canadian National Public Cord Blood Bank.

STUDY DESIGN AND METHODS

A three‐phase validation was developed. CB units were prepared with pentastarch (Phases 1 and 2) or hetastarch (Phase 3). In Phase 1, CB was spiked with approximately 100 colony‐forming units/mL of Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Bacteroides fragilis, and Candida albicans. Plasma (8 mL) and buffy coat (BC; 0.5 and 8 mL) were inoculated into culture bottles. In Phases 2 and 3, a mix of red blood cells (RBCs) and plasma (4 mL each) was used as the inoculant. In Phase 3, Aspergillus brasiliensis was added as a test organism and microbial concentrations in the by‐product RBCs and plasma were determined. The BC fractions were cryopreserved and tested 3 months later.

RESULTS

In Phase 1, bacteria failed to grow in CB units containing antibiotics. Thus, antibiotic‐free units were used for the other phases. C. albicans was not always captured in plasma, but using a mix of RBCs and plasma, all organisms were detected. The use of pentastarch or hetastarch did not affect microbial recovery. C. albicans and A. brasiliensis were preferentially recovered in RBCs and BC. Cryopreservation did not affect microbial survival during CB processing.

CONCLUSIONS

A mix of plasma and RBCs is appropriate for CB sterility testing. Interestingly, fungi preferentially segregate to cellular fractions. The clinical significance of the bactericidal /or bacteriostatic effect of antibiotics in CB merits further investigation.
Dinotefuran/pyriproxyfen/permethrin pemphigus‐like drug reaction in three dogs
Authors: Bizikova Petra , Moriello Karen A. , Linder Keith E. , Sauber Leslie
Published: March 2015

Background

Pemphigus foliaceus (PF) can occur spontaneously or as a reaction pattern associated with cutaneous adverse drug reactions.

Hypothesis/Objectives

To provide clinical, histological and immunological assessments of three dogs that developed cutaneous adverse drug reactions following application of a topical flea and tick control product, which contained dinotefuran, pyriproxyfen and permethrin.

Animals

Three client‐owned dogs.

Results

The dogs exhibited rapid onset of papules, pustules and crusts at the site of application of the flea control product. In two dogs, the lesions became generalized, while the third exhibited a localized phenotype. Both dogs with generalized lesions required immunosuppressive treatment; one achieved remission after 1 year of treatment and one was euthanized due to adverse effects of glucocorticoids. The dog with a localized phenotype was treated with topical glucocorticoids exclusively and achieved remission after 10 months. Histology revealed subcorneal pustular dermatitis, with acantholysis of keratinocytes and focal to multifocal full‐thickness epidermal necrosis. These features are similar to those previously reported for pesticide‐triggered and spontaneous PF. Tissue‐bound IgG was detected in two of three dogs, and autoantibodies targeting canine desmocollin‐1 were identified in the serum of the one dog from which a sample was available.

Conclusions and clinical importance

Cutaneous adverse drug reaction caused by a flea control product containing dinotefuran, pyriproxyfen and permethrin closely resembled those reported for other pesticide‐associated PF‐like cutaneous adverse drug reactions. Although it appears to be a rare entity, clinicians and pathologists should be aware of the potential for flea and tick control products to trigger PF‐like reactions.
The application of cultured epithelial autografts improves survival in burns
Authors: Kym Dohern , Yim Haejun , Yoon Jaechul , Yang Hyeong‐Tae , Cho Yong Suk , Hur Jun , Chun Wook , Kim Jong‐Hyun
Published: March 2015

This prospective observational study was performed to analyze the clinical outcomes of patients with massive burns treated using cultured epithelial autografts (CEAs) and to determine the association of this treatment with survival outcomes. During 2006–2013, total 177 massive‐burns subjects treated with (96 subjects) or without (81 subjects) CEAs. Data were analyzed using the independent t test or chi‐square test. Multivariate logistic regression, Kaplan–Meier survival, and Cox regression analyses were performed to evaluate the factors that influenced mortality. Age, percentage of total body surface area burned, incidence of inhalation injury, allograft‐application rate, Abbreviated Burn Severity Index score, length of hospital stay, and mortality significantly differed between the CEA and noncultured epithelial autograft groups. Mortality and other clinical parameters did not differ between the sheet‐type and spray‐type CEA groups. Allograft application (odds ratio, 4.44; p < 0.01) significantly influenced CEA application. The CEA group showed significantly higher survival rates (p = 0.05). Cultured epithelial autografting had a hazard ratio of 0.55 (p = 0.02) and 0.59 (p = 0.05) according to the uni‐ and multivariate Cox regression analysis, respectively. In conclusion, early and aggressive allograft application is required to facilitate CEA application. Furthermore, the use of CEAs was associated with a lower mortality, but this result should be interpreted with caution as the groups were not randomized.
Surface Wrinkling Patterns of Film–Substrate Systems With a Structured Interface
Authors: Wang Jia-Wen , Li Bo , Cao Yan-Ping , Feng Xi-Qiao
Published: March 2015

Wrinkling of thin films resting on compliant substrates has emerged as a facile means to create well-ordered surface patterns. In this paper, both theoretical analysis and numerical simulations are presented to study the surface wrinkling of a film–substrate system with periodic interfacial structures. It is demonstrated that a variety of novel surface wrinkling patterns can be generated through the introduction of interfacial architectures. These surface patterns can be easily tuned by adjusting two geometric parameters: the lengths of the thin films in the thick and the thin regions. A phase diagram is established for the onset of different wrinkling morphologies with respect to the two geometric dimensions. This study offers a promising route for engineering the surfaces of materials endowed with tunable properties and functions.
The Contribution of the Acetabular Labrum to Hip Joint Stability: A Quantitative Analysis Using a Dynamic Three-Dimensional Robot Model
Authors: Bonner Tara F. , Colbrunn Robb W. , Bottros John J. , Mutnal Amar B. , Greeson Clay B. , Klika Alison K. , van den Bogert Antonie J. , Barsoum Wael K.
Published: March 2015

The acetabular labrum provides mechanical stability to the hip joint in extreme positions where the femoral head is disposed to subluxation. We aimed to quantify the isolated labrum's stabilizing value. Five human cadaveric hips were mounted to a robotic manipulator, and subluxation potential tests were run with and without labrum. Three-dimensional (3D) kinematic data were quantified using the stability index (Colbrunn et al., 2013, “Impingement and Stability of Total Hip Arthroplasty Versus Femoral Head Resurfacing Using a Cadaveric Robotics Model,” J. Orthop. Res., 31(7), pp. 1108–1115). Global and regional stability indices were significantly greater with labrum intact than after total labrectomy for both anterior and posterior provocative positions. In extreme positions, the labrum imparts significant overall mechanical resistance to hip subluxation. Regional stability contributions vary with joint orientation.
Design and Analysis of a Novel Centrifugal Braking Device for a Mechanical Antilock Braking System
Authors: Yang Cheng-Ping , Yang Ming-Shien , Liu Tyng
Published: March 2015

A new concept for a mechanical antilock braking system (ABS) with a centrifugal braking device (CBD), termed a centrifugal ABS (C-ABS), is presented and developed in this paper. This new CBD functions as a brake in which the output braking torque adjusts itself depending on the speed of the output rotation. First, the structure and mechanical models of the entire braking system are introduced and established. Second, a numerical computer program for simulating the operation of the system is developed. The characteristics of the system can be easily identified and can be designed with better performance by using this program to studying the effects of different design parameters. Finally, the difference in the braking performance between the C-ABS and the braking system with or without a traditional ABS is discussed. The simulation results indicate that the C-ABS can prevent the wheel from locking even if excessive operating force is provided while still maintaining acceptable braking performance.
Gradient Span Analysis Method: Application to the Multipoint Aerodynamic Shape Optimization of a Turbine Cascade
Authors: Montanelli Hadrien , Montagnac Marc , Gallard François
Published: March 2015

This paper presents the application of the gradient span analysis (GSA) method to the multipoint optimization of the two-dimensional LS89 turbine distributor. The cost function (total pressure loss) and the constraint (mass flow rate) are computed from the resolution of the Reynolds-averaged Navier–Stokes equations. The penalty method is used to replace the constrained optimization problem with an unconstrained problem. The optimization process is steered by a gradient-based quasi-Newton algorithm. The gradient of the cost function with respect to design variables is obtained with the discrete adjoint method, which ensures an efficient computation time independent of the number of design variables. The GSA method gives a minimal set of operating conditions to insert into the weighted sum model to solve the multipoint optimization problem. The weights associated to these conditions are computed with the utopia point method. The single-point optimization at the nominal condition and the multipoint optimization over a wide range of conditions of the LS89 blade are compared. The comparison shows the strong advantages of the multipoint optimization with the GSA method and utopia-point weighting over the traditional single-point optimization.
Modeling of Response Amplitude Operator for Coupled Sway, Roll and Yaw Motions of a Floating Body in Sinusoidal Waves Using Frequency Based Analysis
Authors: Das Samir K. , Baghfalaki Masoud
Published: March 2015

The paper investigates the characteristics of response amplitude operators (RAO) or transfer function of a floating body in frequency domain for coupled sway, roll and yaw motions in sinusoidal waves. The floating body is considered to be initially at rest and waves act as beam to the floating body with varying frequency (ω) between 0.3 rad/s and 1.2 rad/s. The hydrodynamic coefficients (HC) are computed using strip theory formulation and the general expression of RAO is derived. The behavior of RAO under coupled conditions is examined by considering two asymptotic cases, corresponding to ω→0 and ω→∞. For the intermediate frequency range, analytical expression for system frequency is derived. The effects of viscous damping for uncoupled and coupled transfers have been compared with the result of nonviscous case. A mathematical analogy with respect to Mathieu and Hill equations has been established using frequency based classifications of governing equations. This modeling approach can provide useful guidelines to determine RAO for coupled motions and computing of wave loads and sensitivity analysis with respect to initial conditions of a floating body for the wide range of frequencies.
Analysis of Integrated Coal Gasification System/Compressed-Air Energy Storage Power Plant Concepts
Authors: Nakhamkin M. , Patel M. , Andersson L. , Abitante P. , Cohn A.
Published: March 2015

This paper presents the results of a project targeted at developing cost effective power plant concept with integrated Coal Gasification System (CGS) and with Compressed Air Energy Storage (CAES) plant. The developed concepts, denoted as CGS/CAES, provide for continuous operation of CGS and the reheat turboexpander train which are high temperature components, thus improving their operation and extending life resource. A parametric thermodynamic analysis is performed for several CGS/CAES concepts differentiated by their turbomachinery parameters, CGS arrangements, operating cycles, and hours of daily generation. A qualitative cost estimate is made using a variety of sources including published EPRI reports and extensive in-house cost data. A technical and cost comparison is made to the Integrated Gasification Combined Cycle (IGCC) plant.
Application of Air Saturation to Integrated Coal Gasification/CAES Power Plants
Authors: Nakhamkin M. , Patel M. , Swensen E. , Cohn Arthur , Louks Bert
Published: March 2015

Several studies have recently been conducted with the objective of finding cost-effective applications of coal gasification technology for intermediate load electrical power generation, e.g. 4000 hours per year.
Repowering of a Combined Cycle Plant
Authors: Walder Karen A. , D’Alessio Steven
Published: March 2015

Demand for power in the United States is projected to increase between 2 and 4 percent per year for the next 10 years based on various studies. At the same time, the rise in environmental regulatory restrictions has made it increasingly difficult and expensive for utilities to meet these growing power demands with traditional power sources.

During the 1960’s and 70’s hundreds of gas turbine electric generating units were installed in the United States. Many are now approaching the end of their useful economic lives owing to increased maintenance and fuel costs. With the major advances in both fuel efficiency and exhaust gas emission quality power producers are looking toward the repowering of existing plants with modern gas turbines such as the FT8. (Day and Koehler, 1988)

This paper describes the design of Turbo Power and Marine Systems’ (Turbo Power) FT8® repowering package for the present FT4 powered plant at Public Service Electric and Gas Company’s (PSE&G) Burlington Generating Station. Given the objectives of minimum design effort and minimum field construction time, the retrofit package provides an optimal blending of existing FT4 and standard FT8 equipment. Performance, impact on operation, reliability, and availability of the FT8 industrial gas turbine were also important considerations in the retrofit design.
Developmental Changes in Coordination of Infant Arm and Leg Movements and the Emergence of Function
Authors: Hsu Wen-Hao , Miranda Daniel , Young Diana , Cakert Kelly , Qureshi Mona , Goldfield Eugene
Published: March 2015

We conducted a longitudinal kinematic study of spontaneous arm and leg motions in 4 supine infants at 3, 4½, and 6 months of age. The study addressed two questions: (a) whether there was a longitudinal change in the synchronization of joint rotations at the hips, knees, shoulders, and elbows, indicating that the arms and legs were moving more independently of each other; and (b) whether, during this period, the spatial location of the hands relative to the shoulders was different from that of the feet relative to the hips, indicating that the infants were beginning to use their upper limbs differently than their lower limbs. We found that, in general, the arms and legs were moving more independently of each other by 6 months of age. At the same time, the infants were more likely to hold their hands away from the body in preparation for making contact with an object in the midline, but they brought their feet close to the body to maximize propulsive kicks. Thus, a reorganization of the relative timing of joint rotations appears to be related to the emergence of different arm and leg functions.
Evaluating the Effectiveness of Peer-Scheduled Practice on Motor Learning
Authors: Karlinsky April , Hodges Nicola J.
Published: March 2015

Giving learners a choice over how to schedule practice benefits motor learning. Here we studied peer scheduling to determine whether this benefit is related to the adaptive nature of practice or decisions about how to switch between skills. Forty-eight participants were paired and assigned to self- or peer-scheduled groups. Within each pair, one person (Actor) physically practiced 3 keystroke sequences, each with different timing goals. Self-scheduled Actors chose the sequence before each practice trial while their Partner watched. Peer-scheduled Actors had their practice directed by their Partner. Both peer schedulers and self-schedulers showed performance-dependent practice, making decisions to switch based on timing error. However, peer schedulers generally chose to switch more than self-schedulers although this was not related to retention for either group. Importantly, self-scheduled Actors did not differ in retention from peer-scheduled Actors, but the Actors generally performed with lower error in retention than that of their partners. Peer-scheduled practice was rated as more motivating and enjoyable than self-scheduled practice. In view of the lack of difference in retention and the positive ratings of peer-scheduled practice, we conclude that it is the adaptive nature of practice that is important for learning and that peer-directed practice is an effective alternative practice method to self-directed practice.
Is There an Optimal Age for Learning to Swim?
Authors: Anderson David I. , Rodriguez Alicia
Published: March 2015

Longitudinal records were examined for 272 children who started formal swimming lessons at 3, 4, 5, 6, 7, or 8 years of age. The groups of children were compared on the number of lessons and number of months required to reach three levels of swimming proficiency and the ages at which these levels were reached. Significant differences were found in the ages at which each proficiency level was attained. The younger the age at which children started lessons, the younger they were when they attained Level 1 proficiency. In contrast, the ages at which Level 2 and Level 3 proficiency were attained were more similar, particularly for the younger starters. Significant differences were found for the number of lessons and number of months required to reach Level 1 proficiency and to progress from Level 1 to Level 2 proficiency. The younger the starting age the more lessons and months required to reach each proficiency level. The pattern of findings suggests that the optimum age to begin formal swimming lessons is between 5 and 7 years of age. The findings are discussed relative to the literature on readiness and sensitive periods for learning.
Virus-specific T lymphocytes home to the skin during natural dengue infection
Authors: Rivino Laura , Kumaran Emmanuelle A. , Thein Tun-Linn , Too Chien Tei , Hao Gan Victor Chih , Hanson Brendon J. , Wilder-Smith Annelies , Bertoletti Antonio , J. Gascoigne Nicholas R. , Lye David Chien , Leo Yee Sin , Akbar Arne N. , Kemeny David M. , MacAry Paul A.
Published: March 2015

Circulating virus-specific T lymphocytes may contribute to immune surveillance against dengue in the skin.
Characterization of a Novel Small Molecule That Potentiates β-Lactam Activity against Gram-Positive and Gram-Negative Pathogens
Authors: Nair Dhanalakshmi R. , Monteiro João M. , Memmi Guido , Thanassi Jane , Pucci Michael , Schwartzman Joseph , Pinho Mariana G. , Cheung Ambrose L.
Published: March 2015

In a loss-of-viability screen using small molecules against methicillin-resistant
Staphylococcus aureus
(MRSA) strain USA300 with a sub-MIC of a β-lactam, we found a small molecule, designated DNAC-1, which potentiated the effect of oxacillin (i.e., the MIC of oxacillin decreased from 64 to 0.25 μg/ml). Fluorescence microscopy indicated a disruption in the membrane structures within 15 min of exposure to DNAC-1 at 2× MIC. This permeabilization was accompanied by a rapid loss of membrane potential, as monitored by use of the DiOC
2
(3,3′-diethyloxacarbocyanine iodide) dye. Macromolecular analysis showed the inhibition of staphylococcal cell wall synthesis by DNAC-1. Transmission electron microscopy of treated MRSA USA300 cells revealed a slightly thicker cell wall, together with mesosome-like projections into the cytosol. The exposure of USA300 cells to DNAC-1 was associated with the mislocalization of FtsZ accompanied by the localization of penicillin-binding protein 2 (PBP2) and PBP4 away from the septum, as well as mild activation of the
vraRS
-mediated cell wall stress response. However, DNAC-1 does not have any generalized toxicity toward mammalian host cells. DNAC-1 in combination with ceftriaxone is also effective against an assortment of Gram-negative pathogens. Using a murine subcutaneous coinjection model with 10
8
CFU of USA300 as a challenge inoculum, DNAC-1 alone or DNAC-1 with a sub-MIC of oxacillin resulted in a 6-log reduction in bacterial load and decreased abscess formation compared to the untreated control. We propose that DNAC-1, by exerting a bimodal effect on the cell membrane and cell wall, is a viable candidate in the development of combination therapy against many common bacterial pathogens.
Activities of
N
,
N
′-Diarylurea MMV665852 Analogs against Schistosoma mansoni
Authors: Cowan Noemi , Dätwyler Philipp , Ernst Beat , Wang Chunkai , Vennerstrom Jonathan L. , Spangenberg Thomas , Keiser Jennifer
Published: March 2015

There is an unmet need to discover and develop novel antischistosomal drugs. As exemplified by MMV665852,
N
,
N
′-diarylureas have recently emerged as a promising antischistosomal chemotype. In this study, we evaluated the structure-activity relationships of 46 commercially available analogs of MMV665852 on newly transformed schistosomula (NTS) and adult
Schistosoma mansoni
worms
in vitro
. Active compounds were evaluated with a cytotoxicity assay,
in silico
calculations, metabolic stability studies, and an
in vivo
assay with mice harboring adult
S. mansoni
worms. Of the 46 compounds tested at 33.3 μM, 13 and 14 compounds killed NTS and adult worms, respectively, within 72 h. Nine compounds had 90% inhibitory concentrations (IC
90
s) of ≤10 μM against adult worms, with selectivity indexes of ≥2.8. Their physicochemical properties and permeation through an artificial membrane indicated good to moderate intestinal absorption. Their metabolic stabilities ranged from low to high. Despite satisfactory
in vitro
results and
in silico
predictions, only one compound resulted in a statistically significant worm burden reduction (66%) after administration of a single oral dose of 400 mg/kg of body weight to
S. mansoni
-infected mice. Worm burden reductions of 0 to 43% were observed for the remaining eight compounds tested. In conclusion, several analogs of the
N
,
N
′-diarylurea MMV665852 had high efficacy against
S. mansoni
in vitro
and favorable physicochemical properties for permeation through the intestinal wall. To counteract the low efficacy observed in the mouse model, further investigations should focus on identifying compounds with improved solubility and pharmacokinetic properties.
Simian-Tropic HIV as a Model To Study Drug Resistance against Integrase Inhibitors
Authors: Wares Melissa , Hassounah Said , Mesplède Thibault , Sandstrom Paul A. , Wainberg Mark A.
Published: March 2015

Drug resistance represents a key aspect of human immunodeficiency virus (HIV) treatment failure. It is important to develop nonhuman primate models for studying issues of drug resistance and the persistence and transmission of drug-resistant viruses. However, relatively little work has been conducted using either simian immunodeficiency virus (SIV) or SIV/HIV recombinant viruses for studying resistance against integrase strand transfer inhibitors (INSTIs). Here, we used a T-cell-tropic SIV/HIV recombinant virus in which the capsid and
vif
regions of HIV-1 were replaced with their SIV counterparts (simian-tropic HIV-1 [stHIV-1]
(SCA,SVIF)
) to study the impact of a number of drug resistance substitutions in the integrase coding region at positions E92Q, G118R, E138K, Y143R, S153Y, N155H, and R263K on drug resistance, viral infectivity, and viral replication capacity. Our results show that each of these substitutions exerted effects that were similar to their effects in HIV-1. Substitutions associated with primary resistance against dolutegravir were more detrimental to stHIV-1
(SCA,SVIF)
infectiousness than were resistance substitutions associated with raltegravir and elvitegravir, consistent with data that have been reported for HIV-1. These findings support the role of stHIV-1
(SCA,SVIF)
as a useful model with which to evaluate the role of INSTI resistance substitutions on viral persistence, transmissibility, and pathogenesis in a nonhuman primate model.
Biofilm Formation and Quorum-Sensing-Molecule Production by Clinical Isolates of Serratia liquefaciens
Authors: Remuzgo-Martínez Sara , Lázaro-Díez María , Mayer Celia , Aranzamendi-Zaldumbide Maitane , Padilla Daniel , Calvo Jorge , Marco Francesc , Martínez-Martínez Luis , Icardo José Manuel , Otero Ana , Ramos-Vivas José
Published: March 2015

Serratia
spp. are opportunistic human pathogens responsible for an increasing number of nosocomial infections. However, little is known about the virulence factors and regulatory circuits that may enhance the establishment and long-term survival of
Serratia liquefaciens
in the hospital environment. In this study, two reporter strains,
Chromobacterium violaceum
CV026 and VIR24, and high-resolution triple-quadrupole liquid chromatography–mass spectrometry (LC-MS) were used to detect and to quantify
N
-acyl-homoserine lactone (AHL) quorum-sensing signals in 20
S. liquefaciens
strains isolated from clinical samples. Only four of the strains produced sufficient amounts of AHLs to activate the sensors. Investigation of two of the positive strains by high-performance liquid chromatography (HPLC)-MS confirmed the presence of significant amounts of short-acyl-chain AHLs (
N
-butyryl-
l
-homoserine lactone [C
4
-HSL] and
N
-hexanoyl-
l
-homoserine lactone [C
6
-HSL]) in both strains, which exhibited a complex and strain-specific signal profile that included minor amounts of other short-acyl-chain AHLs (
N
-octanoyl-
l
-homoserine lactone [C
8
-HSL] and
N
-3-oxohexanoyl-
l
-homoserine lactone [OC
6
-HSL]) and long-acyl-chain (C
10
, C
12
, and C
14
) AHLs. No correlation between biofilm formation and the production of large amounts of AHLs could be established. Fimbria-like structures were observed by transmission electron microscopy, and the presence of the type 1 fimbrial adhesin gene
fimH
in all strains was confirmed by PCR. The ability of
S. liquefaciens
to adhere to abiotic surfaces and to form biofilms likely contributes to its persistence in the hospital environment, increasing the probability of causing nosocomial infections. Therefore, a better understanding of the adherence properties of this species will provide greater insights into the diseases it causes.
Analysis of the Candida albicans Phosphoproteome
Authors: Willger S. D. , Liu Z. , Olarte R. A. , Adamo M. E. , Stajich J. E. , Myers L. C. , Kettenbach A. N. , Hogan D. A.
Published: March 2015

Candida albicans
is an important human fungal pathogen in both immunocompetent and immunocompromised individuals.
C. albicans
regulation has been studied in many contexts, including morphological transitions, mating competence, biofilm formation, stress resistance, and cell wall synthesis. Analysis of kinase- and phosphatase-deficient mutants has made it clear that protein phosphorylation plays an important role in the regulation of these pathways. In this study, to further our understanding of phosphorylation in
C. albicans
regulation, we performed a deep analysis of the phosphoproteome in
C. albicans
. We identified 19,590 unique peptides that corresponded to 15,906 unique phosphosites on 2,896 proteins. The ratios of serine, threonine, and tyrosine phosphosites were 80.01%, 18.11%, and 1.81%, respectively. The majority of proteins (2,111) contained at least two detected phosphorylation sites. Consistent with findings in other fungi, cytoskeletal proteins were among the most highly phosphorylated proteins, and there were differences in Gene Ontology (GO) terms for proteins with serine and threonine versus tyrosine phosphorylation sites. This large-scale analysis identified phosphosites in protein components of Mediator, an important transcriptional coregulatory protein complex. A targeted analysis of the phosphosites in Mediator complex proteins confirmed the large-scale studies, and further
in vitro
assays identified a subset of these phosphorylations that were catalyzed by Cdk8 (Ssn3), a kinase within the Mediator complex. These data represent the deepest single analysis of a fungal phosphoproteome and lay the groundwork for future analyses of the
C. albicans
phosphoproteome and specific phosphoproteins.
Structure and Dynamics of the Native HIV-1 Env Trimer
Authors: Munro James B. , Mothes Walther
Published: March 2015

HIV-1/AIDS remains one of the worst pandemics in human history. Despite tremendous efforts, no effective vaccine has been found. Recent reports give new insights into the structure and dynamics of the HIV-1 Env trimer and renew hopes that a better understanding of Env will translate into new vaccine candidates and more-effective antiretroviral therapies.
Vaccination with Adjuvanted Recombinant Neuraminidase Induces Broad Heterologous, but Not Heterosubtypic, Cross-Protection against Influenza Virus Infection in Mice
Authors: Wohlbold Teddy John , Nachbagauer Raffael , Xu Haoming , Tan Gene S. , Hirsh Ariana , Brokstad Karl A. , Cox Rebecca J. , Palese Peter , Krammer Florian
Published: March 2015

In an attempt to assess the cross-protective potential of the influenza virus neuraminidase (NA) as a vaccine antigen, different subtypes of recombinant NA were expressed in a baculovirus system and used to vaccinate mice prior to lethal challenge with homologous, heterologous, or heterosubtypic viruses. Mice immunized with NA of subtype N2 were completely protected from morbidity and mortality in a homologous challenge and displayed significantly reduced viral lung titers. Heterologous challenge with a drifted strain resulted in morbidity but no mortality. Similar results were obtained for challenge experiments with N1 NA. Mice immunized with influenza B virus NA (from B/Yamagata/16/88) displayed no morbidity when sublethally infected with the homologous strain and, importantly, were completely protected from morbidity and mortality when lethally challenged with the prototype Victoria lineage strain or a more recent Victoria lineage isolate. Upon analyzing the NA content in 4 different inactivated-virus vaccine formulations from the 2013-2014 season via Western blot assay and enzyme-linked immunosorbent assay quantification, we found that the amount of NA does indeed vary across vaccine brands. We also measured hemagglutinin (HA) and NA endpoint titers in pre- and postvaccination human serum samples from individuals who received a trivalent inactivated seasonal influenza vaccine from the 2004-2005 season; the induction of NA titers was statistically less pronounced than the induction of HA titers. The demonstrated homologous and heterologous protective capacity of recombinant NA suggests that supplementing vaccine formulations with a standard amount of NA may offer increased protection against influenza virus infection.

IMPORTANCEDespite the existence of vaccine prophylaxis and antiviral therapeutics, the influenza virus continues to cause morbidity and mortality in the human population, emphasizing the continued need for research in the field. While the majority of influenza vaccine strategies target the viral hemagglutinin, the immunodominant antigen on the surface of the influenza virion, antibodies against the viral neuraminidase (NA) have been correlated with less severe disease and decreased viral shedding in humans. Nevertheless, the amount of NA is not standardized in current seasonal vaccines, and the exact breadth of NA-based protection is unknown. Greater insight into the cross-protective potential of influenza virus NA as a vaccine antigen may pave the way for the development of influenza vaccines of greater breadth and efficacy.
Malignant peripheral nerve sheath tumour (MPNST) of mandible: solving the perplexity.
Authors: Patel Shilpa , Pathak Jigna , Dekate Kamlesh , Mohanty Neeta
Published: March 2015

We present an extremely rare case of malignant peripheral nerve sheath tumour (MPNST) in a 30-year-old woman without associated neurofibromatosis 1. The patient presented with an 8 cm×4 cm lesion extending from 46 to the retro molar region involving the ramus of the right mandible associated with regional paraesthesia. Incisional biopsy revealed spindle cells with vesicular nuclei arranged in fascicles leading to a diagnosis of spindle cell lesion. Posterior segmental mandibulectomy was performed under general anaesthesia. On excisional biopsy, a definitive diagnosis of low-grade MPNST was established on the basis of immunohistochemistry. The patient was then lost to follow-up.
A case of endometriosis presenting as an inguinal hernia
Authors: Husain Fahd , Siddiqui Zain Ahmed , Siddiqui Midhat
Published: March 2015

Endometriosis is a common clinical presentation for gynaecologists. Occasionally it can present to general surgeons as a swelling in the groin or abdominal wall. This condition should be included in the differential diagnosis in female patients. A 32-year-old woman with a 2-year history of a painful persistent lump in her right groin was referred to the general surgeons by her general practitioner. She was referred with a diagnosis of a suspected inguinal hernia. MRI excluded a hernia and exploration of the groin and subsequent histology confirmed the lesion to be an endometrial deposit.
Study protocol for a randomised, double-blinded, placebo-controlled, clinical trial ofS-ketamine for pain treatment in patients with chronic pancreatitis (RESET trial)
Authors: Juel Jacob , Olesen Søren Schou , Olesen Anne Estrup , Poulsen Jakob Lykke , Dahan Albert , Wilder-Smith Oliver , Madzak Adnan , Frøkjær Jens Brøndum , Drewes Asbjørn Mohr
Published: March 2015

Introduction

Chronic pancreatitis (CP) is an inflammatory disease that causes irreversible damage to pancreatic tissue. Pain is its most prominent symptom. In the absence of pathology suitable for endoscopic or surgical interventions, pain treatment usually includes opioids. However, opioids often have limited efficacy. Moreover, side effects are common and bothersome. Hence, novel approaches to control pain associated with CP are highly desirable. Sensitisation of the central nervous system is reported to play a key role in pain generation and chronification. Fundamental to the process of central sensitisation is abnormal activation of theN-methyl-d-aspartate receptor, which can be antagonised byS-ketamine. The RESET trial is investigating the analgaesic and antihyperalgesic effect ofS-ketamine in patients with CP.

Methods and analysis

40 patients with CP will be enrolled. Patients are randomised to receive 8 h of intravenousS-ketamine followed by oralS-ketamine, or matching placebo, for 4 weeks. To improve blinding, 1 mg of midazolam will be added to active and placebo treatment. The primary end point is clinical pain relief as assessed by a daily pain diary. Secondary end points include changes in patient-reported outcome measures, opioid consumption and rates of side effects. The end points are registered through the 4-week medication period and for an additional follow-up period of 8 weeks to investigate long-term effects. In addition, experimental pain measures also serves as secondary end points, and neurophysiological imaging parameters are collected. Furthermore, experimental baseline recordings are compared to recordings from a group of healthy controls to evaluate general aspects of pain processing in CP.

Ethics and dissemination

The protocol is approved by the North Denmark Region Committee on Health Research Ethics (N-20130040) and the Danish Health and Medicines Authorities (EudraCT number: 2013-003357-17). The results will be disseminated in peer-reviewed journals and at scientific conferences.

Trial registration number

The study is registered athttp://www.clinicaltrialsregister.eu(EudraCT number 2013-003357-17).
Mindfulness-based stress reduction in patients with interstitial lung diseases: a pilot, single-centre observational study on safety and efficacy
Authors: Sgalla Giacomo , Cerri Stefania , Ferrari Roberto , Ricchieri Maria Pia , Poletti Stefano , Ori Margherita , Garuti Martina , Montanari Gloria , Luppi Fabrizio , Petropulacos Kyriakoula , Richeldi Luca
Published: March 2015

Background

Chronic, progressive respiratory symptoms are associated with great psychological and emotional impact in patients suffering from interstitial lung disease (ILD). This single-centre pilot study evaluated for the first time the safety, feasibility and efficacy of a Mindfulness Based Stress Reduction Program (MBSR) in a group of patients with ILD.

Methods

Prospective observational study set in a university hospital ILD outpatient clinic. Nineteen patients with different ILDs were recruited 2 months prior to the start of the 8-week MBSR program and followed up for 12 months. Primary outcomes were program safety and feasibility, while secondary outcomes were changes in moods and stress (assessed by Profile Of Mood State (POMS) and Perceived Stress Scale (PSS) questionnaires), symptoms (Shortness Of Breath (SOB) and Cough And Sputum Assessment (CASA-Q) questionnaires), lung function and exercise tolerance at 12 months.

Results

Two patients (10.5%) dropped out in the observational period before the start of the MBSR intervention because of non-respiratory causes. All 17 patients who entered the 8-week MBSR program managed to complete it with an adherence average of eight sessions of nine. No adverse events related to the mindfulness training were reported. Statistically significant improvements in the POMS total score and in several individual items of POMS and PSS were observed throughout the study. However, respiratory questionnaire scores, lung function and exercise tolerance did not show a significant difference over time.

Conclusions

An MBSR program appears to be safe and feasible in patients with ILD, and might affect perceived moods and stress producing a positive and lasting improvement in several stress-related negative domains. These findings pave the way to larger (possibly multicentre), randomised, controlled confirmatory trials.
Combination of tumour markers CEA and CA19-9 improves the prognostic prediction in patients with pancreatic cancer
Authors: Reitz Daniel , Gerger Armin , Seidel Julia , Kornprat Peter , Samonigg Hellmut , Stotz Michael , Szkandera Joanna , Pichler Martin
Published: March 2015

Aims

Tumour markers including carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA19-9) are frequently determined at the time of diagnosis in patients with pancreatic cancer. Several studies indicate a prognostic relevance of these markers in pancreatic cancer, but space for improvement with regard to the predictive accuracy and ability is given. In this work, the main focus is on mathematical combinations of these two tumour markers in order to validate an improvement of prognostic test results in terms of sensitivity and specificity.

Methods

This retrospective study includes 393 patients with pancreatic cancer, who were treated between the years 2005 and 2012 at the Division of Oncology, Medical University of Graz, Austria. The goal of this study was to explore whether an appropriate combination of two tumour markers leads to a statistically significant improvement of the prognostic prediction.

Results

Receiver operating characteristic curves comparison analyses with the classification variable cancer-specific survival showed that the mathematical product of two tumour markers (TMproduct= (CEA×CA19-9); area under the curve (AUC)=0.727; 95% CI 0.680 to 0.770) is significantly better than CEA alone (AUC=0.644; 95% CI 0.594 to 0.691; p=0.003) but not significant compared with CA19-9 (AUC=0.710; 95% CI 0.662 to 0.754; p=0.1215). A linear combination of CEA and CA19-9 (TMlinear=(85×CEA+CA19-9); AUC=0.748; 95% CI 0.702 to 0.790) is significantly better than CEA (p<0.0001) as well as CA19-9 alone (p=0.0304).

Conclusions

Mathematical combinations of pretherapeutic tumour markers CEA and CA19-9 are feasible and can significantly improve the prognostic prediction in patients with pancreatic cancer.
Evidence-informed strategies for undergraduate nutrition education: a review
Authors: Newton Genevieve , Bettger William , Buchholz Andrea , Kulak Verena , Racey Megan
Published: March 2015

This review focuses on evidence-informed strategies to enhance learning in undergraduate nutrition education. Here, we describe the general shift in undergraduate education from a teacher-centered model of teaching to a student-centered model and present approaches that have been proposed to address the challenges associated with this shift. We further discuss case-based, project-based, and community-based learning, patient simulation, and virtual clinical trials as educational strategies to improve students’ critical thinking and problem-solving skills; these strategies are well suited to the teaching of undergraduate nutrition. The strategies are defined, and we discuss the potential benefits to students and how they can be applied specifically to the teaching of undergraduate nutrition. Finally, we provide a critical analysis of the limitations associated with these techniques and propose several directions for future research, including research methodologies that may best evaluate teaching strategies in terms of both teaching and learning outcomes. Consideration of these evidence-informed strategies is warranted, given their ability to encourage students to develop relevant skills that will facilitate their transition beyond the university classroom.
Self-pacing increases critical power and improves performance during severe-intensity exercise
Authors: Black Matthew I. , Jones Andrew M. , Bailey Stephen J. , Vanhatalo Anni
Published: March 2015

The parameters of the power-duration relationship for severe-intensity exercise (i.e., the critical power (CP) and the curvature constant (W′)) are related to the kinetics of pulmonary O2 uptake, which may be altered by pacing strategy. We tested the hypothesis that the CP would be higher when derived from a series of self-paced time-trials (TT) than when derived from the conventional series of constant work-rate (CWR) exercise tests. Ten male subjects (age, 21.5 ± 1.9 years; mass, 75.2 ± 11.5 kg) completed 3–4 CWR and 3–4 TT prediction trial protocols on a cycle ergometer for the determination of the CP and W′. The CP derived from the TT protocol (265 ± 44 W) was greater (P < 0.05) than the CP derived from the CWR protocol (250 ± 47 W), while the W′ was not different between protocols (TT: 18.1 ± 5.7 kJ, CWR: 20.6 ± 7.4 kJ, P > 0.05). The mean response time of pulmonary O2 uptake was shorter during the TTs than the CWR trials (TT: 34 ± 16, CWR: 39 ± 19 s, P < 0.05). The CP was correlated with the total O2 consumed in the first 60 s across both protocols (r = 0.88, P < 0.05, n = 20). These results suggest that in comparison with the conventional CWR exercise protocol, a self-selected pacing strategy enhances CP and improves severe-intensity exercise performance. The greater CP during TT compared with CWR exercise has important implications for performance prediction, suggesting that TT completion times may be overestimated by CP and W′ parameters derived from CWR protocols.
A possible molecular mechanism of hearing loss during cerebral ischemia in mice
Authors: Kamat Pradip Kumar , Kalani Anuradha , Metreveli Naira , Tyagi Suresh C. , Tyagi Neetu
Published: March 2015

Ischemic brain stroke is a leading cause of disability and includes hearing loss. Clinical reports have also suggested that there is hearing loss in stroke patients but the mechanism was not determined. Therefore, we hypothesized that hearing loss after cerebral ischemia may be associated with changes to the synapse, gap junction, and sodium channel (NaC) proteins. Ischemia–reperfusion injury was induced in wild-type mice (I/R group). The lesion volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining of the brain sections. BBB disruption was confirmed by Evans blue staining and leakage of bovine serum albumin labeled with fluorescein isothiocyanate (BSA-FITC). We found that brain edema, infarct size, and permeability were increased in ischemic mice as compared with the sham-operated group. Caspase-3, caspase-9, and TUNEL-positive cells were increased in I/R mice, indicating neuronal apoptosis. Moreover, there were increased expressions of matrix metalloprotease’s (MMP-2, -3, -9, and -13), interleukin (IL)-6, and decreased expressions of tight junction proteins (TJP) in the I/R group, as compared with the sham group, which signifies inflammation and BBB disruption. We also observed decreased levels of post-synaptic density protein-95 (PSD-95), synapse-associated protein 97 (SAP-97), connexin-43, NaC-α, and NaC-β, and increased expression of connexin-45, whereas no substantial change was observed in connexin-26 expression in the I/R group. Interestingly, auditory response was reduced in the I/R mice, indicating hearing loss. These data suggest that hearing loss in ischemic mice was primarily due to alterations in connexin, synapses, and NaC channels.
Analysis of acetohydroxyacid synthase1 gene in chickpea conferring resistance to imazamox herbicide
Authors: Jain Parul , Tar’an Bunyamin
Published: March 2015

Chickpea (Cicer arietinum L.) production in the Canadian prairies is challenging due to a lack of effective weed management mainly because of poor competition ability of the crop and limited registered herbicide options. Chickpea genotype with resistance to imidazolinone (IMI) herbicides has been identified. A point mutation in the acetohydroxyacid synthase1 (AHAS1) gene at C581 to T581, resulting in an amino acid substitution from Ala194 to Val194 (position 205, standardized to arabidopsis), confers the resistance to imazamox in chickpea. However, the molecular mechanism leading to the resistance is not fully understood. In many plant species, contrasting transcription levels of AHAS gene has been implicated in the resistant and susceptible genotypes in response to IMI. The objectives of this research were to compare the AHAS gene expression and AHAS enzyme activity in resistant and susceptible chickpea cultivars in response to imazamox herbicide treatment. Results from RT–qPCR indicated that there is no significant change in the transcript levels of AHAS1 between the susceptible and the resistant genotypes in response to imazamox treatment. Protein hydrophobic cluster analysis, protein-ligand docking analysis, and AHAS enzyme activity assay all indicated that the resistance to imazamox in chickpea is due to the alteration of interaction of the AHAS1 enzyme with the imazamox herbicide.
Crossed products by actions of finite groups with the Rokhlin property
Authors: Santiago Luis
Published: March 2015

We introduce and study a Rokhlin-type property for actions of finite groups on (not necessarily unital) C*-algebras. We show that the corresponding crossed product C*-algebras can be locally approximated by C*-algebras that are stably isomorphic to closed two-sided ideals of the given algebra. We then use this result to prove that several classes of C*-algebras are closed under crossed products by finite group actions with this Rokhlin property.