bluuebunny/crossref_metadata_2025 huggingface dataset:
Theory and validation of the motion resistance mechanism of four-caster manual vehicles
Authors: Abraham Brian B , Davidson Robert I , Johnson Garth R
Published: July 2013

The four-caster manually manoeuvred vehicle is a crucial device for goods movement and disability transport. While there are manual handling related health and safety concerns, no dynamical theoretical-empirical investigation exists. Theoretical examination demonstrates that, in loose terms, the motion resistance effects are affected by vehicle-frame translational velocity direction: the proportion of the moment effect to translational effect produced by motion resistance varies in a highly non-linear way depending on the vehicle-frame velocity direction. An empirical study is devised from the theory. As the intention was to investigate the presence of this phenomenon in real use, human operators were used: they made planar manoeuvres from static equilibrium with a self-selected load while attempting to maintain 11 (maximum) different centres of zero velocity which related to the velocity directions. Results demonstrate that (1) the proportion of moment motion resistance effect to translational motion resistance effect does vary and (2) it is motion resistance rather than inertial forces which are the first-order effect. These results are an essential first step in understanding the manoeuvring difficulties and health and safety issues which arise with these vehicles.
The commonplace journey methodology: exploring outdoor recreation activities through theoretically-informed reflective practice
Authors: Mullins Philip M
Published: July 2013

This paper describes the foundations, introduces a conceptual model, and discusses uses of the commonplace journey methodology, an innovative and mobile qualitative research and pedagogical approach based on existential hermeneutic phenomenology. Using this mobile methodology, the researcher placed a theoretical approach to human–environment relations from outside the scholarly field of outdoor recreation and education in dialogue with travellers’ lived experience, activities, and understandings during an extended canoe expedition. Examples from the data and findings are used to further describe the processes, benefits, and challenges of this phenomenological methodology. Finally, the author describes four analytical techniques used to anchor interpretation and written theoretical accounts in lived practice and physical context.
Disclosure of Intimate Partner Violence to Informal Social Support Network Members
Authors: Sylaska Kateryna M. , Edwards Katie M.
Published: July 2013

This article presents a review of the published literature to date on rates, experiences, and correlates of victims’ disclosure of or help seeking for intimate partner violence to informal social support network members (e.g., friends, family, classmates, and coworkers). Research indicates that the majority of individuals disclose to at least one informal support and that victims’ disclosure is associated with a number of demographic (e.g., victims’ sex, age, race), intrapersonal (e.g., victims’ feelings of shame/embarrassment, perception of control over abuse), and situational (e.g., violence frequency and severity, if abuse is witnessed) factors. Following disclosure, victims experience a wide range of positive (e.g., believing the victim’s reports, validating the victim’s experiences) and negative (e.g. disbelieving, blaming the victim) social reactions, with positive reactions rated as the most common and most helpful forms of support by victims. Finally, a review of psychological correlates associated with reactions to disclosure indicates that positive social reactions are associated with more psychological health benefits and fewer negative health symptoms, whereas negative social reactions were associated with increased negative psychological health symptoms. Future research methodologies and implications for violence prevention, intervention, and policy are discussed.
Using Text-to-Speech Reading Support for an Adult With Mild Aphasia and Cognitive Impairment
Authors: Harvey Judy , Hux Karen , Snell Jeffry
Published: July 2013

This single case study served to examine text-to-speech (TTS) effects on reading rate and comprehension in an individual with mild aphasia and cognitive impairment. Findings showed faster reading, given TTS presented at a normal speaking rate, but no significant comprehension changes. TTS may support reading in people with aphasia when time limitations exist.
Redefining Individual Growth and Development Indicators
Authors: Bradfield Tracy A. , Besner Amanda C. , Wackerle-Hollman Alisha K. , Albano Anthony D. , Rodriguez Michael C. , McConnell Scott R.
Published: July 2013

Language skills developed during preschool contribute strongly to later reading and academic achievement. Effective preschool assessment and intervention should focus on core components of language development, specifically oral language skills. The Early Language and Literacy Individual Growth and Development Indicators (IGDIs) are a set of measures that have demonstrated utility in language and early literacy assessment, evaluation, and intervention studies. The purpose of this article is to describe two studies conducted to build on the existing oral language IGDI, Picture Naming, to increase utility for instructional decision making, particularly within an early childhood Response to Intervention framework. Study 1 outlines the initial development and piloting of potential measures and Study 2 describes the revision and continued analysis of the most promising measures. Results of Study 1 and Study 2 indicate that Picture Naming has continued utility as a measure of oral language skill development and that one newly developed oral language IGDI, Definitional Vocabulary, has potential utility.
Randomized Trial of Observation and Execution of Upper Extremity Actions Versus Action Alone in Children With Unilateral Cerebral Palsy
Authors: Sgandurra Giuseppina , Ferrari Adriano , Cossu Giuseppe , Guzzetta Andrea , Fogassi Leonardo , Cioni Giovanni
Published: July 2013

Background. The properties of the mirror neuron system suggest a new type of upper limb (UL) rehabilitation in children with unilateral cerebral palsy (UCP), based on observation of action therapy followed by execution of a variety of observed movements (AOT). Objective. We tested the effects of AOT in the Upper Limb Children Action Observation Training (UP-CAT) trial. Methods. In a randomized, evaluator-blinded, block-designed trial, 24 UCP children with mild to moderate hand impairment were assigned to 2 groups. The experimental group observed, 1 hour per day for 3 consecutive weeks, video sequences of unimanual or bimanual goal-directed actions and subsequently executed observed actions with the hemiparetic UL or both ULs. The control group performed the same actions in the same order as the experimental sample, but had watched computer games. The Assisting Hand Assessment (AHA) scale was the primary outcome measure; the Melbourne assessment and ABILHAND-Kids were secondary ones. Outcomes were assessed at 1 week (T1), 8 weeks (T2), and 24 weeks (T3) after the end of the training. Results. The experimental group improved more ( P = .008) in score changes for the AHA at the primary endpoints T1 ( P = .008), T2 ( P = .019), and T3 ( P = .049). No between-group significant changes were found for ABILHAND-Kids or Melbourne assessment. Conclusions. UP-CAT improved daily UL activities in UCP children, suggesting a new rehabilitation approach based on a neurophysiological model of motor learning.
Treatment of complex neurovascular lesions: an interdisciplinary angio suite approach
Authors: Dammann Philipp , Breyer Tobias , Wrede Karsten H. , Stein Klaus-Peter , Wanke Isabel , Grams Astrid E. , Gizewski Elke R. , Schlamann Marc , Forsting Michael , Sandalcioglu I. Erol , Sure Ulrich
Published: July 2013

Objective:

The objective of this study was to analyse our initial experience using an interdisciplinary angio suite approach to neurosurgical treatment of complex neurovascular lesions and expound technical feasibility and possible applications.

Subjects:

Six out of 451 patients with cranial or spinal neurovascular lesions were surgically treated in the angio suite (biplane angiographic system) during a 28-month observation period. Clinical baseline data, radiological and intraoperative findings as well as clinical and radiological outcome were assessed.

Results:

A ventral spinal perimedullary arteriovenous malformation, a ventral spinal perimedullary fistula, two diffuse frontal dural arteriovenous fistulas, a multifocal temporal arteriovenous malformation and a partially embolized fronto-temporo-basal dural arteriovenous fistula were successfully treated with angiographically confirmed complete occlusion and unimpaired neurological condition of the patients at the 12-month follow up.

Conclusion:

This study demonstrates the feasibility of this approach and points out possible indications, namely ventrally located spinal lesions and diffuse, deep seated cranial lesions.
Acts, Persons, and Intuitions
Authors: Uhlmann Eric Luis , Zhu Luke [Lei]
Published: July 2013

Negative gut reactions to harmless-but-offensive transgressions can be driven by inferences about the moral character of the agent more so than condemnation of the act itself. Dissociations between moral judgments of acts and persons emerged, such that participants viewed a harmless-but-offensive transgression to be a less immoral act than a harmful act, yet more indicative of poor moral character. Participants were more likely to become “morally dumbfounded” when asked to justify their judgments of a harmless-but-offensive act relative to a harmful act. However, they were significantly less likely to become morally dumbfounded when asked to justify character judgments of persons who engaged in the harmless-but-offensive transgression, an effect based in part on the information-rich nature of such behaviors. Distinguishing between evaluations of acts and persons helps account for both moral outrage over harmless transgressions and when individuals are (and are not) at a loss to explain their own judgments.
Genetic predispositions to childhood leukemia
Authors: Stieglitz Elliot , Loh Mignon L.
Published: July 2013

While the majority of leukemia cases occur in the absence of any known predisposing factor, there are germline mutations that significantly increase the risk of developing hematopoietic malignancies in childhood. In this review article, we describe a number of these mutations and their clinical features. These predispositions can be broadly classified as those leading to bone marrow failure, those involving tumor suppressor genes, DNA repair defects, immunodeficiencies or other congenital syndromes associated with transient myeloid disorders. While leukemia can develop as a secondary event in the aforementioned syndromes, there are also several syndromes that specifically lead to the development of leukemia as their primary phenotype. Many of the genes discussed in this review can also be somatically mutated in other cancers, highlighting the importance of understanding shared alterations and mechanisms underpinning syndromic and sporadic leukemia.
Comparison of the effects of Sertindole and Olanzapine on Cognition (SEROLA): a double-blind randomized 12-week study of patients diagnosed with schizophrenia
Authors: Ernst Nielsen René , Odur Florence , Østergaard Torben , Munk-Jørgensen Povl , Nielsen Jimmi
Published: July 2013

Objective:

To assess the cognitive effects of sertindole and olanzapine in patients diagnosed with schizophrenia. Cognition was the primary outcome of the study.

Method:

This was a 12-week double-blinded randomized clinical controlled trial. Participants were randomized to either 16–24 mg of sertindole or 10–20 mg of olanzapine.

Results:

The study had a low recruitment rate ( N = 9) and was terminated before the expected number of patients was reached. No significant differences between groups were found at study end on any of the 32 cognitive subtests. A simple sign test did not show any of the comparator drugs trending towards being superior on the majority of tests. Mean change on Positive and Negative Syndrome Scale (PANSS) total and PANSS subscales from baseline to end of study were not significantly different between treatment groups. Similar results on cognition and PANSS was seen on completers and last observation carried forward analysis.

Conclusion:

In this study we did not find any significant differences between sertindole or olanzapine on PANSS subscales or neurocognitive tests in a population consisting of patients diagnosed with schizophrenia.
Pain, Sleep Disturbances, and Functional Limitations in People Living with HIV/AIDS-Associated Distal Sensory Peripheral Neuropathy
Authors: Sandoval Roberto , Roddey Toni , Giordano Thomas P. , Mitchell Katy , Kelley Carolyn
Published: July 2013

Background:

Pain, sleep, and functional disturbances are a common occurrence in people living with HIV/AIDS-related distal sensory peripheral neuropathy (PLWHA-DSPN) yet lack group classification and quantification.

Methods:

A total of 46 PLWHA-DSPN were recruited, as part of a 2-group intervention study, to complete the Neuropathic Pain Scale and the Pittsburgh Sleep Quality Index (PSQI) questionnaires. The participant’s performance during a forward reach task and walking distance in 6 minutes was recorded as a measure of function.

Results:

The pain (60.77 ± 17.85) and sleep (14.62 ± 4.28) scores denote marked pain and sleep disturbances, compared to sero-negative, age-matched individuals. The ambulation distance was limited (243.99 ± 141.04 m) and inversely associated with the PSQI-sleep efficiency subscale ( rs = −.35, P < .05). The average reaching distances measured (36.07 ± 7.37 cm) were similar to sero-negative, age-matched individuals. Pain, sleep, and functional measures exhibited significant associations.

Conclusions:

The data collected suggest that PLWHA-DSPN report moderate-to-severe pain and significant sleep disturbances and exhibit limited ambulation distances.
Gait Asymmetries Persist 1 Year After Anterior Cruciate Ligament Reconstruction
Authors: White Kathleen , Logerstedt David , Snyder-Mackler Lynn
Published: July 2013

Background:

After anterior cruciate ligament reconstruction (ACLR), motivation to return to previous levels of activity is high. Very few studies have used return-to-activity criteria to determine when to permit athletic play. Return-to-activity measures objectively evaluate functional limb symmetry; however, previous biomechanical studies have found gait deviations in these individuals that persist up to 2 years after surgery.

Purpose:

To evaluate gait biomechanics in a specific cohort of ACL patients 1 year after surgery and retrospectively compare individuals who pass return-to-activity criteria 6 months after surgery with those who fail.

Study Design:

Prospective analysis.

Methods:

A total of 40 athletes who participated regularly (>50 h/y) in cutting, jumping, and pivoting activities and who sustained an isolated, unilateral ACL rupture were included in this study. All participants underwent reconstruction by the same surgeon and received individualized postoperative rehabilitation. Performance-based and self-report data were measured 6 months after surgery to assess readiness to return to activity (90% outcome required to pass); 20 subjects passed return-to-activity criteria and 20 subjects did not. Motion analysis was performed 1 year after surgery, and knee flexion angles, moments, and excursions were measured during gait and evaluated for all subjects.

Results:

There was no limb × group interaction or effect of group for all measures. Decreased knee measures were seen on the involved limb compared with the uninvolved limb for all subjects, and failed subjects demonstrated larger differences between limbs.

Conclusion:

Patients continued to demonstrate biomechanical limb asymmetries 1 year after ACLR, regardless of performance-based measures at 6 months. Early return to activity did not ensure limb symmetry at 1 year.

Clinical Relevance:

Gait asymmetries were seen in all subjects 1 year after surgery regardless of status at 6 months. Potentially prolonging athlete’s timelines for returning to activity may prove beneficial for a successful return to activity as well as for long-term knee function.
Smectite clay from the Sabga deposit (Cameroon): mineralogical and physicochemical properties
Authors: Mache J. R. , Signing P. , Njoya A. , Kunyukubundo F. , Mbey J. A. , Njopwouo D. , Fagel N.
Published: July 2013

The physicochemical and mineralogical characterization of the <250 μm particle-size fraction from six clay-rich samples from the Sabga deposit (north-west, Cameroon) were carried out to evaluate their potential applications. The major clay mineral is dioctahedral smectite and minor kaolinite is present in three of the clay samples. Cristobalite, feldspars, ilmenite and heulandite are accessory minerals. Application of the Greene-Kelly test revealed that the smectite present is montmorillonite. The chemical composition (wt.%) of the bulk clays consists of (66–70%) SiO2, (13–16%) Al2O3and (2–7%) Fe2O3. Physico-chemical characterization of the clays showed that the cation exchange capacity (CEC) and the specific surface area range from 38 to 46 meq/100 g and from 33 to 90 m2/g respectively. The physical and chemical properties are fully compatible with potential uses in environmental applications. After purification and chemical modification, these materials could also be used in refining edible oil as adsorbent, waste water treatment and wine technology.
Rasip1 regulates vertebrate vascular endothelial junction stability through Epac1-Rap1 signaling
Authors: Wilson Christopher W. , Parker Leon H. , Hall Christopher J. , Smyczek Tanya , Mak Judy , Crow Ailey , Posthuma George , De Mazière Ann , Sagolla Meredith , Chalouni Cecile , Vitorino Philip , Roose-Girma Merone , Warming Søren , Klumperman Judith , Crosier Philip S. , Ye Weilan
Published: July 2013

Key Points

RASIP1 is required for stabilizing nascent patent blood vessels in both mice and zebrafish. RASIP1 is a dynamic effector of EPAC1-RAP1 signaling that controls actin bundling and restricts junction remodeling in vitro and in vivo.
Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes
Authors: Dubovsky Jason A. , Beckwith Kyle A. , Natarajan Gayathri , Woyach Jennifer A. , Jaglowski Samantha , Zhong Yiming , Hessler Joshua D. , Liu Ta-Ming , Chang Betty Y. , Larkin Karilyn M. , Stefanovski Matthew R. , Chappell Danielle L. , Frissora Frank W. , Smith Lisa L. , Smucker Kelly A. , Flynn Joseph M. , Jones Jeffrey A. , Andritsos Leslie A. , Maddocks Kami , Lehman Amy M. , Furman Richard , Sharman Jeff , Mishra Anjali , Caligiuri Michael A. , Satoskar Abhay R. , Buggy Joseph J. , Muthusamy Natarajan , Johnson Amy J. , Byrd John C.
Published: July 2013

Key Points

Ibrutinib is the first clinically viable irreversible ITK inhibitor. Ibrutinib inhibits the formation of Th2 but not Th1 immunity.
Boundedness of the maximal operator in the local Morrey-Lorentz spaces
Authors: Aykol Canay , Guliyev Vagif S , Serbetci Ayhan
Published: July 2013

In this paper we define a new class of functions called local Morrey-Lorentz spaces

M

p
,
q
;
λ

loc

(

R
n

)

,

0
<
p
,
q
≤
∞

and

0
≤
λ
≤
1

. These spaces generalize Lorentz spaces such that

M

p
,
q
;
0

loc

(

R
n

)
=

L

p
,
q

(

R
n

)

. We show that in the case

λ
<
0

or

λ
>
1

, the space

M

p
,
q
;
λ

loc

(

R
n

)

is trivial, and in the limiting case

λ
=
1

, the space

M

p
,
q
;
1

loc

(

R
n

)

is the classical Lorentz space

Λ

∞
,

t

1
p

−

1
q

(

R
n

)

. We show that for

0
<
q
≤
p
<
∞

and

0
<
λ
≤

q
p

, the local Morrey-Lorentz spaces

M

p
,
q
;
λ

loc

(

R
n

)

are equal to weak Lebesgue spaces

W

L

1
p

−

λ
q

(

R
n

)

. We get an embedding between local Morrey-Lorentz spaces and Lorentz-Morrey spaces. Furthermore, we obtain the boundedness of the maximal operator in the local Morrey-Lorentz spaces.

MSC:42B20, 42B25, 42B35, 47G10.
Discovery of structural alterations in solid tumor oligodendroglioma by single molecule analysis
Authors: Ray Mohana , Goldstein Steve , Zhou Shiguo , Potamousis Konstantinos , Sarkar Deepayan , Newton Michael A , Esterberg Elizabeth , Kendziorski Christina , Bogler Oliver , Schwartz David C
Published: July 2013

Background

Solid tumors present a panoply of genomic alterations, from single base changes to the gain or loss of entire chromosomes. Although aberrations at the two extremes of this spectrum are readily defined, comprehensive discernment of the complex and disperse mutational spectrum of cancer genomes remains a significant challenge for current genome analysis platforms. In this context, high throughput, single molecule platforms like Optical Mapping offer a unique perspective.

Results

Using measurements from large ensembles of individual DNA molecules, we have discovered genomic structural alterations in the solid tumor oligodendroglioma. Over a thousand structural variants were identified in each tumor sample, without any prior hypotheses, and often in genomic regions deemed intractable by other technologies. These findings were then validated by comprehensive comparisons to variants reported in external and internal databases, and by selected experimental corroborations. Alterations range in size from under 5 kb to hundreds of kilobases, and comprise insertions, deletions, inversions and compound events. Candidate mutations were scored at sub-genic resolution and unambiguously reveal structural details at aberrant loci.

Conclusions

The Optical Mapping system provides a rich description of the complex genomes of solid tumors, including sequence level aberrations, structural alterations and copy number variants that power generation of functional hypotheses for oligodendroglioma genetics.
Sequence polymorphisms of rfbT among the Vibrio cholerae O1 strains in the Ogawa and Inaba serotype shifts
Authors: Liang Weili , Wang Luxi , Liang Pu , Zheng Xiao , Zhou Haijian , Zhang Jingyun , Zhang Lijuan , Kan Biao
Published: July 2013

Background

Vibrio cholerae serogroup O1 has two major serotypes, Ogawa and Inaba, which may alternate among cholera epidemics. The rfbT gene is responsible for the conversion between the two serotypes. In this study, we surveyed the sequence variance of rfbT in the Ogawa and Inaba strains in China over a 48-year (1961-2008) period in which serotype shifts occurred among epidemic years.

Results

Various mutation events including single nucleotide, short fragment insertions/deletions and transposases insertions, were found in the rfbT gene of the Inaba strains. Ectopically introducing an intact rfbT could overcome the mutations by converting the Inaba serotype to the Ogawa serotype, suggesting the effects of these mutations on the function of RfbT. Characteristic rfbT mutations were recognized in the Inaba strains among Inaba serotype dominant epidemic years which were separate from the Ogawa dominant epidemics. Three distinguishable mutation sites in rfbT between the classical and the El Tor biotype strains were identified and could serve as biotype-specific biomarkers.

Conclusions

Our results provide a comprehensive picture of the rfbT gene mutations among the V. cholerae O1 strains in different epidemic periods, which could be further used as the tracing markers in clonality analysis and dissemination surveillance of the epidemic strains.
Characterization of temperature and light effects on the defense response phenotypes associated with the maize Rp1-D21autoactive resistance gene
Authors: Negeri Adisu , Wang Guan-Feng , Benavente Larissa , Kibiti Cromwell M , Chaikam Vijay , Johal Guri , Balint-Kurti Peter
Published: July 2013

Background

Rp1 is a complex locus of maize, which carries a set of genes controlling race-specific resistance to the common rust fungus, Puccinia sorghi. The resistance response includes the “Hypersensitive response” (HR), a rapid response triggered by a pathogen recognition event that includes localized cell death at the point of pathogen penetration and the induction of pathogenesis associated genes. The Rp1-D21gene is an autoactive allelic variant at the Rp1 locus, causing spontaneous activation of the HR response, in the absence of pathogenesis. Previously we have shown that the severity of the phenotype conferred by Rp1-D21 is highly dependent on genetic background.

Results

In this study we show that the phenotype conferred by Rp1-D21 is highly dependent on temperature, with lower temperatures favoring the expression of the HR lesion phenotype. This temperature effect was observed in all the 14 genetic backgrounds tested. Significant interactions between the temperature effects and genetic background were observed. When plants were grown at temperatures above 30°C, the spontaneous HR phenotype conferred by Rp1-D21 was entirely suppressed. Furthermore, this phenotype could be restored or suppressed by alternately reducing and increasing the temperature appropriately. Light was also required for the expression of this phenotype. By examining the expression of genes associated with the defense response we showed that, at temperatures above 30°C, the Rp1-D21 phenotype was suppressed at both the phenotypic and molecular level.

Conclusions

We have shown that the lesion phenotype conferred by maize autoactive resistance gene Rp1-D21 is temperature sensitive in a reversible manner, that the temperature-sensitivity phenotype interacts with genetic background and that the phenotype is light sensitive. This is the first detailed demonstration of this phenomenon in monocots and also the first demonstration of the interaction of this effect with genetic background. The use of temperature shifts to induce a massive and synchronous HR in plants carrying the Rp1-D21 genes will be valuable in identifying components of the defense response pathway.
Selection of an adjuvant for seasonal influenza vaccine in elderly people: modelling immunogenicity from a randomized trial
Authors: Rümke Hans C , Richardus Jan Hendrik , Rombo Lars , Pauksens Karlis , Plaßmann Georg , Durand Christelle , Devaster Jeanne-Marie , Dewé Walthère , Oostvogels Lidia
Published: July 2013

Background

Improved influenza vaccines are needed to reduce influenza-associated complications in older adults. The aim of this study was to identify the optimal formulation of adjuvanted seasonal influenza vaccine for use in elderly people.

Methods

This observer-blind, randomized study assessed the optimal formulation of adjuvanted seasonal influenza vaccine based on immunogenicity and safety in participants aged ≥65 years. Participants were randomized (~200 per group) to receive one dose of non-adjuvanted vaccine or one of eight formulations of vaccine formulated with a squalene and tocopherol oil-in-water emulsion-based Adjuvant System (AS03C, AS03B or AS03A, with 2.97, 5.93 and 11.86 mg tocopherol, respectively) together with the immunostimulant monophosphoryl lipid A (MPL, doses of 0, 25 or 50 mg). Hemagglutination-inhibition (HI) antibody responses and T-cell responses were assessed on Day 0 and 21 days post-vaccination. The ratio of HI-based geometric mean titers in adjuvanted versus non-adjuvanted vaccine groups were calculated and the lower limit of the 90% confidence interval was transformed into a desirability index (a value between 0 and 1) in an experimental domain for each vaccine strain, and plotted in relation to the AS03 and MPL dose combination in the formulation. This model was used to assess the optimal formulation based on HI antibody titers. Reactogenicity and safety were also assessed. The immunogenicity and safety analyses were used to evaluate the optimal formulation of adjuvanted vaccine.

Results

In the HI antibody-based model, an AS03 dose–response was evident; responses against the A/H1N1 and A/H3N2 strains were higher for all adjuvanted formulations versus non-adjuvanted vaccine, and for the AS03A-MPL25, AS03B-MPL25 and AS03B-MPL50 formulations against the B strain. Modelling using more stringent criteria (post hoc) showed a clear dose-range effect for the AS03 component against all strains, whereas MPL showed a limited effect. Higher T-cell responses for adjuvanted versus non-adjuvanted vaccine were observed for all except two formulations (AS03C and AS03B-MPL25). Reactogenicity increased with increasing AS03 dosage, and with MPL. No safety concerns were raised.

Conclusions

Five formulations containing AS03A or AS03B were identified as potential candidates to improve immune responses to influenza vaccination; AS03B without MPL showed the best balance between improved immunogenicity and acceptable reactogenicity.

Trial registration

This trial is registered at ClinicalTrials.gov, NCT00540592
Sequence variants in oxytocin pathway genes and preterm birth: a candidate gene association study
Authors: Kim Jinsil , Stirling Kara J , Cooper Margaret E , Ascoli Mario , Momany Allison M , McDonald Erin L , Ryckman Kelli K , Rhea Lindsey , Schaa Kendra L , Cosentino Viviana , Gadow Enrique , Saleme Cesar , Shi Min , Hallman Mikko , Plunkett Jevon , Teramo Kari A , Muglia Louis J , Feenstra Bjarke , Geller Frank , Boyd Heather A , Melbye Mads , Marazita Mary L , Dagle John M , Murray Jeffrey C
Published: July 2013

Background

Preterm birth (PTB) is a complex disorder associated with significant neonatal mortality and morbidity and long-term adverse health consequences. Multiple lines of evidence suggest that genetic factors play an important role in its etiology. This study was designed to identify genetic variation associated with PTB in oxytocin pathway genes whose role in parturition is well known.

Methods

To identify common genetic variants predisposing to PTB, we genotyped 16 single nucleotide polymorphisms (SNPs) in the oxytocin (OXT), oxytocin receptor (OXTR), and leucyl/cystinyl aminopeptidase (LNPEP) genes in 651 case infants from the U.S. and one or both of their parents. In addition, we examined the role of rare genetic variation in susceptibility to PTB by conducting direct sequence analysis of OXTR in 1394 cases and 1112 controls from the U.S., Argentina, Denmark, and Finland. This study was further extended to maternal triads (maternal grandparents-mother of a case infant, N=309). We also performed in vitro analysis of selected rare OXTR missense variants to evaluate their functional importance.

Results

Maternal genetic effect analysis of the SNP genotype data revealed four SNPs in LNPEP that show significant association with prematurity. In our case–control sequence analysis, we detected fourteen coding variants in exon 3 of OXTR, all but four of which were found in cases only. Of the fourteen variants, three were previously unreported novel rare variants. When the sequence data from the maternal triads were analyzed using the transmission disequilibrium test, two common missense SNPs (rs4686302 and rs237902) in OXTR showed suggestive association for three gestational age subgroups. In vitro functional assays showed a significant difference in ligand binding between wild-type and two mutant receptors.

Conclusions

Our study suggests an association between maternal common polymorphisms in LNPEP and susceptibility to PTB. Maternal OXTR missense SNPs rs4686302 and rs237902 may have gestational age-dependent effects on prematurity. Most of the OXTR rare variants identified do not appear to significantly contribute to the risk of PTB, but those shown to affect receptor function in our in vitro study warrant further investigation. Future studies with larger sample sizes are needed to confirm the findings of this study.
Nuclear factor kappa B modulates apoptosis in the brain endothelial cells and intravascular leukocytes of fatal cerebral malaria
Authors: Punsawad Chuchard , Maneerat Yaowapa , Chaisri Urai , Nantavisai Kwannan , Viriyavejakul Parnpen
Published: July 2013

Background

Cerebral malaria (CM) caused byPlasmodium falciparumis known to be associated with the sequestration of parasitized red blood cells (PRBCs) in the microvasculature and the release of soluble cytokines. In addition, the involvement of signaling molecules has gained wide interest in the pathogenesis of CM. An important signaling factor, nuclear factor kappa B (NF-κB) is known to regulate apoptosis. This work aimed to study the expression of NF-κB p65 and its correlation with apoptosis in the brain of fatal CM.

Methods

The expression of NF-κB p65 and cleaved caspase-3 in the brain of fatalP. falciparummalaria cases was investigated by immunohistochemistry. Histopathological features were analysed together with the correlations of NF-κB p65 and cleaved caspase-3 expression.

Results

NF-κB p65 activation and cleaved caspase-3 expression were significantly increased in the neurons, glial cells, vascular endothelial cells (ECs) and intravascular leukocytes of the brain in fatal CM, compared with the control brain (p< 0.001) and non-cerebral malaria (NCM) (p= 0.034). The percentage of neurons that expressed nuclear NF-κB p65 showed a positive correlation with the total score of histopathological changes (rs= 0.678;p= 0.045). Significant positive correlations were established between vascular ECs NF-κB index and ECs apoptotic index (rs= 0.717;p= 0.030) and between intravascular leukocytes NF-κB index and leukocytes apoptotic index (rs= 0.696;p= 0.037) in fatal CM.

Conclusions

This study documented that NF-κB p65 is one of the signaling factors that modulates apoptosis in the brain ECs and intravascular leukocytes of fatal CM.
Prevalence of drug resistance associated mutations in Plasmodium vivax against sulphadoxine-pyrimethamine in southern Pakistan
Authors: Raza Afsheen , Ghanchi Najia K , Khan Muhammad Shahzeb , Beg Mohammad Asim
Published: July 2013

Background

In Pakistan, Plasmodium vivax and Plasmodium falciparum co-exist and usage of sulphadoxine-pyrimethamine (SP) against P. falciparum exposes P. vivax to the drug leading to generation of resistant alleles. The main aim of this study was to investigate frequency distribution of drug resistance associated mutations in pvdhfr, pvdhps genes and provide baseline molecular epidemiological data on SP-associated resistance in P. vivax from southern Pakistan.

Methods

From January 2008 to May 2009, a total of 150 samples were collected from patients tested slide-positive for P. vivax, at the Aga Khan University Hospital, Karachi, or its collection units located in Baluchistan and Sindh Province. Nested PCR using pvdhfr and pvdhps specific primers was performed for all samples.91.3% (137/150) of the samples were tested PCR positive of which 87.3% (131/137) were successfully sequenced. Sample sequencing data was analysed and compared against wild type reference sequences.

Results

In dhfr, mutations were observed at codons F57L, S58R and S117N/T. Novel non-synonymous mutations were observed at codon positions N50I, G114R and E119K while a synonymous mutation was observed at codon position 69Y. In dhps, mutations were observed at codon position A383G and A553G while novel non-synonymous mutations were observed at codon positions S373T, E380K, P384L, N389T, V392D, T393P, D459A, M601I, A651D and A661V.

Conclusion

This is the first report from southern Pakistan on SP resistance in clinical isolates of P. vivax. Results from this study confirm that diverse drug resistant alleles are circulating within this region.
Alterations in neuronal morphology and synaptophysin expression in the rat brain as a result of changes in dietary n-6: n-3 fatty acid ratios
Authors: Hajjar Toktam , Goh Yong Meng , Rajion Mohamed Ali , Vidyadaran Sharmili , Li Tan Ai , Ebrahimi Mahdi
Published: July 2013

Background

Polyunsaturated fatty acids (PUFA) play important roles in brain fatty acid composition and behavior through their effects on neuronal properties and gene expression. The hippocampus plays an important role in the formation of memory, especially spatial memory and navigation. This study was conducted to examine the effects of PUFA and specifically different dietary n-6: n-3 fatty acid ratios (FAR) on the number and size of hippocampal neurons and the expression of synaptophysin protein in the hippocampus of rats.

Methods

Forty 3-week old male Sprague–Dawley rats were allotted into 4 groups. The animals received experimental diets with different n-6: n-3 FAR of either 65:1, 26.5:1, 22:1 or 4.5:1 for 14 weeks.

Results

The results showed that a lowering dietary n-6: n-3 FAR supplementation can increase the number and size of neurons. Moreover, lowering the dietary n-6: n-3 FAR led to an increase in the expression of the pre-synaptic protein synaptophysin in the CA1 hippocampal subregion of the rat brain.

Conclusions

These findings support the notion that decreasing the dietary n-6: n-3 FAR will lead to an intensified hippocampal synaptophysin expression and increased neuron size and proliferation in the rat brain.
Probing the orientation of electrostatically immobilized cytochrome C by time of flight secondary ion mass spectrometry and sum frequency generation spectroscopy
Authors: Baio Joe E , Weidner Tobias , Ramey Dennis , Pruzinsky Leah , Castner David G
Published: July 2013

By taking advantage of the electron pathway through the heme group in cytochrome c (CytoC) electrochemists have built sensors based upon CytoC immobilized onto metal electrodes. Previous studies have shown that the electron transfer rate through the protein is a function of the position of this heme group with respect to the electrode surface. In this study a detailed examination of CytoC orientation when electrostatically immobilized onto both amine (NH3+) and carboxyl (COO-) functionalized gold is presented. Protein coverage, on both surfaces, was monitored by the change in the atomic % N, as determined by x-ray photoelectron spectroscopy. Spectral features within the in situ sum frequency generation vibrational spectra, acquired for the protein interacting with positively and negatively charged surfaces, indicates that these electrostatic interactions do induce the protein into a well ordered film. Time of flight secondary ion mass spectrometry data demonstrated a clear separation between the two samples based on the intensity differences of secondary ions stemming from amino acids located asymmetrically within CytoC (cysteine: C2H6NS+; glutamic acid: C4H6NO+ and C4H8NO2+; leucine: C5H12N+). For a more quantitative examination of orientation, we developed a ratio comparing the sum of the intensities of secondary-ions stemming from the amino acid residues at either end of the protein. The 50 % increase in this ratio, observed between the protein covered NH3+ and COO- substrates, indicates opposite orientations of the CytoC on the two different surfaces.
Effects of exercise and diet interventions on obesity-related sleep disorders in men: study protocol for a randomized controlled trial
Authors: Tan Xiao , Saarinen Antti , Mikkola Tuija M , Tenhunen Jarkko , Martinmäki Samu , Rahikainen Aki , Cheng Shumei , Eklund Niklas , Pekkala Satu , Wiklund Petri , Munukka Eveliina , Wen Xinfei , Cong Fengyu , Wang Xi , Zhang Yajun , Tarkka Ina , Sun Yining , Partinen Markku , Alen Markku , Cheng Sulin
Published: July 2013

Background

Sleep is essential for normal and healthy living. Lack of good quality sleep affects physical, mental and emotional functions. Currently, the treatments of obesity-related sleep disorders focus more on suppressing sleep-related symptoms pharmaceutically and are often accompanied by side effects. Thus, there is urgent need for alternative ways to combat chronic sleep disorders. This study will investigate underlying mechanisms of the effects of exercise and diet intervention on obesity-related sleep disorders, the role of gut microbiota in relation to poor quality of sleep and day-time sleepiness, as well as the levels of hormones responsible for sleep-wake cycle regulation.

Methods/design

Participants consist of 330 (target sample) Finnish men aged 30 to 65 years. Among them, we attempt to randomize 180 (target sample) with sleep disorders into exercise and diet intervention. After screening and physician examination, 101 men with sleep disorders are included and are randomly assigned into three groups: exercise (n = 33), diet (n = 35), and control (n = 33). In addition, we attempt to recruit a target number of 150 healthy men without sleep disorders as the reference group. The exercise group undergoes a six-month individualized progressive aerobic exercise program based on initial fitness level. The diet group follows a six month specific individualized diet program. The control group and reference group are asked to maintain their normal activity and diet during intervention. Measurements are taken before and after the intervention. Primary outcomes include objective sleep measurements by polysomnography and a home-based non-contact sleep monitoring system, and subjective sleep evaluation by questionnaires. Secondary outcome measures include anthropometry, body composition, fitness, sleep disorder-related lifestyle risk factors, composition of gut microbiota and adipose tissue metabolism, as well as specific hormone and neurotranmitter levels and inflammatory biomarkers from venous blood samples.

Discussion

It is expected that the improvement of sleep quality after exercise and diet intervention will be evident both in subjective and objective measures of quality of sleep. Additionally, the change of sleep quality induced by exercise and diet intervention is expected to be related to the changes in specific hormones and inflammatory biomarkers, and in the composition of gut microbiota.

Trial registration

Current Controlled Trials ISRCTN77172005
A practical strategy for responding to a case of lymphatic filariasis post-elimination in Pacific Islands
Authors: Harrington Humpress , Asugeni James , Jimuru Christopher , Gwalaa John , Ribeyro Elmer , Bradbury Richard , Joseph Hayley , Melrose Wayne , MacLaren David , Speare Rick
Published: July 2013

Background

Lymphatic filariasis (LF) due to Wuchereria bancrofti is being eliminated from Oceania under the Pacific Elimination of Lymphatic Filariasis Programme. LF was endemic in Solomon Islands but in the 2010-2020 Strategic Plan of the Global Programme to Eliminate LF, Solomon Islands was listed as non-endemic for LF. In countries now declared free of LF an important question is what monitoring strategy should be used to detect any residual foci of LF?

This paper describes how a new case of elephantiasis in a post-elimination setting may be used as a trigger to initiate a local survey for LF.

Methods

The index case, a 44 year old male, presented to Atoifi Adventist Hospital, Malaita, Solomon Islands in April 2011 with elephantiasis of the lower leg. Persistent swelling had commenced 16 months previously. He was negative for antigen by TropBio Og4C3 ELISA and for microfilaria. A week later a survey of 197 people aged from 1 year to 68 years was conducted at Alasi, the index case’s village, by a research team from Atoifi Adventist Hospital and Atoifi College of Nursing. This represented 66.3% of the village population. Blood was collected between 22:00 and 03:00 by finger-prick and made into thick smears to detect microfilaria and collected onto filter paper for W. bancrofti antigen tests. A second group of 110 specimens was similarly collected from residents of the Hospital campus and inpatients. W. bancrofti antigen was tested for using the Trop-Bio Og4C3 test.

Results

One sample (1/307) from an 18 year old male from Alsai was positive for W. bancrofti antigen. No samples were positive for microfilaria. Although antigen-positivity indicated a live worm, the case was regarded as having been acquired some years previously.

Conclusions

We propose that when LF has been eliminated from a country, a case of elephantiasis should be a trigger to conduct a survey of the case’s community using a decision pathway. W. bancrofti antigen should be tested for with screening for microfilariae in antigen positive cases. The field survey was designed and conducted by local researchers, highlighting the value of local research capacity in remote areas.
Differential expression of PTEN gene correlates with phenotypic heterogeneity in three cases of patients showing clinical manifestations of PTEN hamartoma tumour syndrome
Authors: Paparo Lorella , Rossi Giovanni Battista , Delrio Paolo , Rega Daniela , Duraturo Francesca , Liccardo Raffaella , Debellis Mario , Izzo Paola , De Rosa Marina
Published: July 2013

Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS) and proteus syndrome are disorders known as PTEN hamartoma tumour syndrome (PHTS), that can show remarkable clinical overlap and are all caused by germline PTEN mutations.

We here present two families, one affected by CS and the other affected by BRRS, both carriers of specific pathogenetic missense mutation in exon 5 of PTEN gene, within the catalitic domain. Both PHTS families exhibited extremely variable phenotypes, showing inter- and intra- familial variability. One of the two characterised mutations, the c.320A- > T; p.107Asp- > Val, identified in the CS family, was not previously described in the literature. Furthermore, the BRRS family, carrier of the c.406 T- > C; p.136Cys- > Arg mutation, shows a substantial alteration of PTEN protein expression that well correlates with intra-familial phenotypic variability.

Finally, we describe an apparently sporadic case of an 80-year-old man, with a very low level of PTEN mRNA and protein expression, both in healthy and tumour colon mucosa, associated with a very atypical phenotype. He developed a metastatic colorectal carcinoma, macrocephaly and pheochromocytoma.

According to literature data, our observations confirm that PTEN mutations of catalytic domain can cause different syndromes. We suggest that PTEN expression could represent one of the mechanisms involved in the remarkable heterogeneity of the clinical PHTS manifestations within affected families. Furthermore, constitutive strong decrease of PTEN expression in colon normal mucosa could be associated with late onset of colorectal cancer.
Increasing protein production by directed vector backbone evolution
Authors: Jakob Felix , Lehmann Christian , Martinez Ronny , Schwaneberg Ulrich
Published: July 2013

Recombinant protein production in prokaryotic and eukaryotic organisms was a key enabling technology for the rapid development of industrial and molecular biotechnology. However, despite all progress the improvement of protein production is an ongoing challenge and of high importance for cost-effective enzyme production. With the epMEGAWHOP mutagenesis protocol for vector backbone optimization we report a novel directed evolution based approach to increase protein production levels by randomly introducing mutations in the vector backbone. In the current study we validate the epMEGAWHOP mutagenesis protocol for three different expression systems. The latter demonstrated the general applicability of the epMEGAWHOP method. Cellulase and lipase production was doubled in one round of directed evolution by random mutagenesis of pET28a(+) and pET22b(+) vector backbones. Protease production using the vector pHY300PLK was increased ~4-times with an average of ~1.25 mutations per kb vector backbone. The epMEGAWHOP does not require any rational understanding of the expression machinery and can generally be applied to enzymes, expression vectors and related hosts. epMEGAWHOP is therefore from our point of view a robust, rapid and straight forward alternative for increasing protein production in general and for biotechnological applications.