bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of soil compaction and tire mobility with finite element method
Authors: Li Hao , Schindler Christian
Published: May 2013

Soil compaction, as a form of soil degradation, accounts for the increase of soil strength and the reduction of soil production capability. Two finite element tire models were developed based on the real geometry and structure of a Bridgestone bias tire. With a single wheel tester, field experiments were performed to validate the finite element tire–soil interaction models. The influence of axle load and inflation pressure on the soil compaction was studied with a finite element tire model using coarse meshes, which improves the computation efficiency without degrading the simulation accuracy. Tire mobility such as drawbar pull, rolling resistance and lateral force generated inside the tire–soil contact patch is an important index for the performance of off-road vehicles. The relationship between the slip ratio, the slip angle and the tire mobility was investigated through the simulations carried out with the other finite element tire model using fine meshes.
Monitoring of a civil structure’s state based on noncontact measurements
Authors: Kohut Piotr , Holak Krzysztof , Uhl Tadeusz , Ortyl Łukasz , Owerko Tomasz , Kuras Przemysław , Kocierz Rafał
Published: May 2013

In this article, the comparison of two noncontact measurement methods dedicated to civil engineering structures’ state examination is presented. The vision-based method computes the displacement field of the analyzed structure by means of the digital image correlation coefficient. The system consists of one or more high-resolution digital cameras mounted on a head or on portable tripods. The developed methodology and created software application embedded in an MS-Windows operating system are presented. The second system measures the deflection of the structures by means of a radar interferometer. In both cases, it is possible to measure many points on the structure simultaneously. This article presents a comparison of the displacement field measurement performed on a field setup, as well as the span of a steel bridge designed for tram traffic. Both systems are described, with special attention given to their application in measurements of civil engineering structures. This article demonstrates a preliminary test performed to verify both of the noncontact systems in relation to high-accuracy measurement devices, the precise surveying level, and the electronic dial indicator of displacement. The experiment was designed intentionally to simulate the geometric conditions of the real structure, but the displacement values were generated and controlled by the operator. As a key study, a steel viaduct subjected to an operational load was measured, as a type of structure for which the observation is required in terms of structural health monitoring. It was subjected to the operational load caused by tram traffic. Both examined systems were applied. The accuracy analysis of both systems was investigated, and the obtained results were discussed.
Portraits of People With Dementia
Authors: Webster Gemma , Fels Deborah
Published: May 2013

Communication difficulties associated with late-stage dementia can make it difficult for care staff in residential environments to get to know people with dementia. This lack of knowledge can have a negative effect on the social environment of residential facilities, which can have a detrimental effect on the health and well-being of the residents and the job satisfaction of the staff. In this article, we discuss the creation of portraits of people with dementia to aid care staff in understanding the individual. The major findings of these case studies include that it is possible for families to create portraits of their relatives within a relatively short period of time and families found the process enjoyable and a good trigger for reminiscence.
Spontaneous and Induced Nontransgenic Animal Models of AD
Authors: Kaushal Alka , Wani Willayat Yousuf , Anand R. , Gill Kiran Dip
Published: May 2013

Alzheimer’s disease (AD), the most common neurodegenerative and dementing disorder, is characterized by extracellular amyloid deposition, intracellular neurofibrillary tangle formation, and neuronal loss. We are still behind in AD research in terms of knowledge regarding understanding its pathophysiology and designing therapeutics because of the lack of an accurate animal model for AD. A complete animal model of AD should imitate all the cognitive, behavioral, and neuropathological features of the disease. Partial models are currently in use, which only mimic specific and not all of the components of AD pathology. Currently the transgenic animals are the popular models for AD research, but different genetic backgrounds of these transgenic animals remain a major confounding factor. This review attempts to summarize the current literature on nontransgenic animal models of AD and to highlight the potential of exploiting spontaneous and induced animal models for neuropathological, neurochemical, neurobehavioral, and neuroprotective studies of AD.
Adaptive adjustment of the randomization ratio using historical control data
Authors: Hobbs Brian P , Carlin Bradley P , Sargent Daniel J
Published: May 2013

Background

Prospective trial design often occurs in the presence of ‘acceptable’ historical control data. Typically, these data are only utilized for treatment comparison in a posteriori retrospective analysis to estimate population-averaged effects in a random-effects meta-analysis.

Purpose

We propose and investigate an adaptive trial design in the context of an actual randomized controlled colorectal cancer trial. This trial, originally reported by Goldberg et al., succeeded a similar trial reported by Saltz et al., and used a control therapy identical to that tested (and found beneficial) in the Saltz trial.

Methods

The proposed trial implements an adaptive randomization procedure for allocating patients aimed at balancing total information (concurrent and historical) among the study arms. This is accomplished by assigning more patients to receive the novel therapy in the absence of strong evidence for heterogeneity among the concurrent and historical controls. Allocation probabilities adapt as a function of the effective historical sample size (EHSS), characterizing relative informativeness defined in the context of a piecewise exponential model for evaluating time to disease progression. Commensurate priors are utilized to assess historical and concurrent heterogeneity at interim analyses and to borrow strength from the historical data in the final analysis. The adaptive trial’s frequentist properties are simulated using the actual patient-level historical control data from the Saltz trial and the actual enrollment dates for patients enrolled into the Goldberg trial.

Results

Assessing concurrent and historical heterogeneity at interim analyses and balancing total information with the adaptive randomization procedure lead to trials that on average assign more new patients to the novel treatment when the historical controls are unbiased or slightly biased compared to the concurrent controls. Large magnitudes of bias lead to approximately equal allocation of patients among the treatment arms. Using the proposed commensurate prior model to borrow strength from the historical data, after balancing total information with the adaptive randomization procedure, provides admissible estimators of the novel treatment effect with desirable bias-variance trade-offs.

Limitations

Adaptive randomization methods in general are sensitive to population drift and more suitable for trials that initiate with gradual enrollment. Balancing information among study arms in time-to-event analyses is difficult in the presence of informative right-censoring.

Conclusions

The proposed design could prove important in trials that follow recent evaluations of a control therapy. Efficient use of the historical controls is especially important in contexts where reliance on preexisting information is unavoidable because the control therapy is exceptionally hazardous, expensive, or the disease is rare.
Active citizenship, education and service learning
Authors: Birdwell Jonathan , Scott Ralph , Horley Edward
Published: May 2013

This article explores how active citizenship can be encouraged through education and community action. It proposes that service learning and a renewed focus on voluntarism can both promote social cohesion between different ethnic and cultural groups while also fostering among the population a greater understanding of and commitment to civic culture. It reviews the international evidence on service programmes and the newly created National Citizen Service programme in the United Kingdom, arguing for a greater role for service learning in the citizen educational offer.
Atypical Presentation of Verrucous Carcinoma
Authors: Penera Keith E. , Manji Karim A. , Craig Alex B. , Grootegoed Rebecca A. , Leaming Troy R. , Wirth Garrett A.
Published: May 2013

Verrucous carcinoma is a slow-growing lesion that is most often found on the weight-bearing surface of the foot and should be considered in the differential diagnosis for chronic nonhealing wounds in the diabetic neuropathic population. Accurate diagnosis may be difficult initially and often requires repeat histopathologic evaluation by an experienced pathologist. Verrucous carcinoma can invade deeper tissues; however, extension to bone is a rare occurrence. The authors present a case report of an atypical verrucous carcinoma on the dorsal aspect of the foot and a review of the literature. Studies suggest that multiple therapies exist and recurrence does occur; however, this is less likely with wide excision and more so with Mohs’ surgery. With a high clinical suspicion and thorough histopathologic exam, bone involvement and amputation may be avoided.

Levels of Evidence: Therapeutic, Level IV
Absence of the Fourth Tendon of the Flexor Digitorum Brevis Muscle
Authors: Bernhard Andrew , Miller Josh , Keeler Jason , Siesel Kathy , Bridges Evan
Published: May 2013

This study was undertaken to help confirm the percentages concerning the presence or absence of the flexor digitorum brevis muscle tendon to the fifth toe. We also hope to be able to determine the presence based on gender and nationality. It is known to be absent occasionally; however, there is no definitive study dedicated to its prevalence. Using a pool of 60 cadavers, 97 total feet were included in our analysis. Of these feet, 47 (48%) lacked a flexor digitorum brevis tendon to the fifth toe at all. Furthermore, 25 (26%) had notably small tendons to the fifth toe. The final 25 (26%) had what the researchers deemed present tendons. This information could be helpful in surgical planning, including tendon transfer techniques, and biomechanical evaluations. Further research would need to be conducted as this was a cadaveric study.

Levels of Evidence: Cadaver/anatomy research, Level V
Body Mass Index and Achilles Tendonitis
Authors: Klein Erin E. , Weil Lowell , Weil Lowell Scott , Fleischer Adam E.
Published: May 2013

Introduction. High body mass index (BMI) has been implicated as an etiologic agent in Achilles tendonitis (AT) and may contribute to poorer treatment outcomes. The purpose of this study was to better elucidate the role of BMI in both the development and treatment of AT. Methods. A matched case–control (1:1) study design was used. Matching criteria were age, gender, and year of presentation. Consecutive patients who presented with a diagnosis of AT between 2002 and 2011 at a single foot and ankle specialty clinic were identified. Patients who presented with other foot pain at the same clinic served as controls (CG). The AT group was further stratified into treatment responders and nonresponders. The main effect measure for both analyses was an adjusted odds ratio. Results. A total of 944 patients (472 AT; 472 CG) were included. AT patients had higher BMI than those in the CG (30.2 ± 6.5 vs 25.9 ± 5.3, P < .001). Overweight and obese patients were 2.6 to 6.6 times more likely than those with a normal BMI to present with Achilles tendonitis ( P < .001). There was also elevated risk of presenting with AT at higher BMI categories (Mantel–Haenszel χ2 = 8.074, P = .004). However, only age, not BMI, correlated with having failed conservative treatment among the AT group, with patients older than 65 years at the greatest risk (odds ratio = 2.4, 95% confidence interval = 1.5 to 4.1, P < .001). Conclusion. BMI plays a role in the development of AT but does not appear to influence patient response to conservative treatment.

Levels of Evidence: Prognostic, Level II
The Correlation of Achilles Tendinopathy and Body Mass Index
Authors: Scott Ryan T. , Hyer Christopher F. , Granata Angela
Published: May 2013

With this study we intend to determine if there is a correlation between body mass index (BMI) and Achilles tendon pathology. A retrospective chart review of 197 patients was performed with CPT codes of Achilles tendinosis/tendonitis. These 197 patients were then compared with 100 random new patient encounters excluding Achilles pathology, plantar fasciitis, and surgical consults. Statistical analysis was then performed to identify correlation of BMI to incidence of Achilles tendinosis compared with patients without Achilles pathology. A total of 197 Achilles tendon pathology patients (113 male, 84 female) were analyzed and had a mean age of 52.77 ± 11.8 years (21-82) with a BMI of 34.69 ± 7.54 (17.9-75.9). The control group had a mean age of 42.74 ± 12.1 years (21-78) and mean BMI of 30.56 ± 7.55 (19.7-61.5). A significant difference was found in mean BMI between the Achilles tendinopathy group versus the control group ( P < .001). There was a very significant difference in age noted between the 2 cohorts (52.77 years vs 42.74 years, P < .001), perhaps reenforcing the involvement of age-related degenerative changes. In this study, patients with Achilles pathology exhibited a significantly higher BMI than non-Achilles patients ( P < .001) even after accounting for age.

Levels of Evidence: Prognostic Level II
Tinderet volcano, Kenya: an altered natrocarbonatite locality?
Authors: Zaitsev A. N. , Wenzel T. , Vennemann T. , Markl G.
Published: May 2013

The Tinderet volcano (19.9 to 5.5 Ma), located within the Kavirondo rift in Kenya, contains blocks of carbonatite lavas with calcite, minor apatite, fluorite, spinel-group minerals, accessory perovskite and 'plumbopyrochlore'; nyerereite is present as inclusions in the perovskite. At least four types of calcite are present in the carbonatite lavas; they differ in morphology, composition and origin. The dominant variety is secondary type-II calcite, which is enriched in sodium (up to 1.1 wt.% Na2O) and strontium (up to 1.3 wt.% SrO). The spinel-group minerals are manganese-bearing and include Mn-rich magnetite, magnesioferrite and jacobsite. Oxygen isotope data for bulk carbonatite samples (δ18O = +16.2 % to +22.6 % VSMOW) support a low crystallization temperature for the secondary calcite. Petrographic, mineralogical and isotopic data indicate that the Tinderet carbonatites are similar to natrocarbonatites from the Oldoinyo Lengai and Kerimasi volcanoes that have altered and recrystallized to form calcite carbonatites. These data support the hypothesis that some of the Tinderet carbonatites were originally alkali-rich rocks which contained primary nyerereite.
Crystal chemistry and formation mechanism of non-stoichiometric monoclinic K-jarosites
Authors: Grey I. E. , Scarlett N. V. Y. , Brand H. E. A.
Published: May 2013

Syntheses in acidified hydrothermal (HT) solutions (1 N H2SO4or stronger) produce monoclinic non-stoichiometric K-jarosites which contain Fe-site vacancies with long-range order. Syntheses in non-acidified HT solutions produce rhombohedral K-jarosites which contain relatively large numbers of Fe-site vacancies with no long-range order. Increasing the [Fe]/[K] ratio, reaction temperature and reaction time in non-acidified solutions promotes the formation of monoclinic jarosites which contain Fe-site vacancies with short-range order. A structural model including details of the ordering of the Fe-site vacancies was obtained by refinement of single-crystal synchrotron data from one of the HT synthesis products; this model was used to refine synchrotron powder X-ray diffraction data from products synthesized at different reaction times, temperatures and [Fe]/[K] ratios. Thermal and chemical analyses are consistent with a model for non-stoichiometry in which domains of stoichiometric jarosite are intergrown with butlerite-like iron-deficient domains with a composition [Fe2(SO4)2(OH)2(H2O)4]. It was found that heterogeneous nucleation of monoclinic jarosite on Si disks is preceded by the formation of an oriented film of Maus's Salt, K5Fe3O(SO4)6·10H2O, as a precursor phase, and that this transforms topotactically into oriented jarosite, which contains butlerite-like layers parallel to the disk surface. Structural models for the transformation of Maus's Salt into jarosite are proposed.
Kudryavtsevaite, Na3MgFe3+Ti4O12, a new kimberlitic mineral
Authors: Anashkin S. , Bovkun A. , Bindi L. , Garanin V. , Litvin Y.
Published: May 2013

Kudryavtsevaite, ideally Na3MgFe3+Ti4O12, is a new mineral from kimberlitic rocks of the Orapa area, Botswana. It occurs as rare prismatic crystals, up to 100 μm m across, associated with Mg-rich ilmenite, freudenbergite and ulvöspinel. Kudryavtsevaite is opaque with a vitreous lustre and shows a black streak. It is brittle; the Vickers hardness (VHN100) is 901 kg mm−2 (range: 876–925) (Mohs hardness ∼6). In reflected light, kudryavtsevaite is moderately bireflectant and very weakly pleochroic from dark grey to a slightly bluish grey. Under crossed polars, it is very weakly anisotropic with greyish-bluish rotation tints. Internal reflections are absent. Reflectance values (%), Rmin and Rmax, are: 21.3, 25.4 (471.1 nm), 20.6, 24.1 (548.3 nm), 20.0, 23.5 (586.6 nm) and 19.1, 22.4 (652.3 nm).

Kudryavtsevaite is orthorhombic, space group Pnma, with a = 27.714(1), b = 2.9881(3), c = 11.3564(6) Å, V = 940.5(1) Å3, and Z = 4. The crystal structure [R1 = 0.0168 for 819 reflections with I > 2σ(I)] consists of edge-sharing and corner-sharing chains composed of Mg, Fe3+ and Ti atoms coordinated by six atoms of oxygen and running along the b axis, with Na filling the tunnels formed by the chains. The eight strongest powder-diffraction lines [d in Å (I/I0) (hkl)] are: 7.17 (100) (301), 4.84 (70) (302), 2.973 (35) (901), 2.841 (50) (004), 2.706 (50) (902), 2.541 (50) (312), 2.450 (70) (611), and 2.296 (45) (612). The average results of 12 electron microprobe analyses gave (wt.%): Na2O 16.46(15), CaO 1.01(3), MgO 5.31(5), Fe2O3 22.24(32), Cr2O3 1.05(6), Al2O3 0.03(2), TiO2 53.81(50), total 99.91, corresponding to the empirical formula (Na2.89Ca0.10)Σ2.99(Ti3.67Fe1.523+Mg0.72Cr0.08)Σ5.99O12, or ideally Na3MgFe3+Ti4O12.

The new mineral has been approved by the IMA-CNMNC and named for Galina Kudryavtseva (1947–2006), a well known Russian mineralogist and founder of the Diamond Mineralogy Laboratory and scientific school for investigation of diamond mineralogy and geochemistry at the Lomonosov State University in Moscow, Russia.
Bond-valence constraints around the O1 site of tourmaline
Authors: Bosi F.
Published: May 2013

The stabilities of possible Y(R3+ + R2+ + Li+) clusters around the W anion (O1 site) of the tourmaline structure were checked using the bond-valence approach. Arrangements involving R3+ = Al3+ or Fe3+ and R2+ = (Fe, Mn, Mg)2+ were all found to be stable. Structural data show a strong linear correlation between the mean formal valence (MFV) of the Y cations and the long-range average bond valence sum (BVS) at the O1 site, as estimated from bond-valence parameters. This correlation is observed for all chemical compositions of tourmaline, except for fluor-buergerite where the O3 site is dominated by oxygen anions. Results show that the long-range site populations of the Y and O1 sites are related to each other by valence constraints described by the empirical and theoretical equations: BVS(O1) = [0.99 MFV(Y) − 1.20] and MFV(O1) = [1.00 MFV(Y) − 1.00], respectively. The systematic deviation of the empirical equation from the ideal one is ascribed to the occurrence of bond strain involving the O1 site. An important implication of the correlation between MFV(Y) and BVS(O1) is that the (OH) content at the O1 site may be estimated by the equation W(OH) = 2 − [1.01 BVS(O1)] − 0.21 − F.
NrasG12D/+ promotes leukemogenesis by aberrantly regulating hematopoietic stem cell functions
Authors: Wang Jinyong , Kong Guangyao , Liu Yangang , Du Juan , Chang Yuan-I , Tey Sin Ruow , Zhang Xinmin , Ranheim Erik A. , Saba-El-Leil Marc K. , Meloche Sylvain , Damnernsawad Alisa , Zhang Jingfang , Zhang Jing
Published: May 2013

Key Points

NrasG12D/+ induces proliferation and increases self-renewal and myeloid differentiation bias in HSCs. ERK1/2 is constitutively hyperactivated in NrasG12D/+ HSCs and downregulation of the MEK/ERK signaling attenuates NrasG12D/+ HSC phenotypes.
FLT3 inhibitor-induced neutrophilic dermatosis
Authors: Fathi Amir T. , Le Long , Hasserjian Robert P. , Sadrzadeh Hossein , Levis Mark , Chen Yi-Bin
Published: May 2013

Key Points

Infiltrating FLT3-ITD neutrophils identified in skin confirms terminal differentiation of FLT3-ITD blasts after FLT3 inhibitor therapy. Neutrophilic dermatosis after FLT3 inhibition may be a manifestation of a differentiation syndrome associated with this treatment.
Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia
Authors: Van Vlierberghe Pieter , Ambesi-Impiombato Alberto , De Keersmaecker Kim , Hadler Michael , Paietta Elisabeth , Tallman Martin S. , Rowe Jacob M. , Forne Carles , Rue Montserrat , Ferrando Adolfo A.
Published: May 2013

Key Points

Integrated genomic profiling identifies high-risk adult T-ALL patients with poor response to intensified chemotherapy.
Headache associated with cough: a review
Authors: Cordenier Ann , De Hertogh Willem , De Keyser Jacques , Versijpt Jan
Published: May 2013

Headache only triggered by coughing is a rather uncommon condition. The aim of the present review is to present an overview of the diagnosis, clinical characteristics, pathophysiology and treatment of both primary and symptomatic cough headache and discuss other relevant headache disorders affected by coughing. The diagnosis of primary cough headache is made when headache is brought on and occurs only in association with coughing, straining or a Valsalva manoeuvre and in the absence of any abnormalities on neuro-imaging. In case an underlying pathology is identified as a cause of the headache, the diagnosis of symptomatic cough headache is made. The vast majority of these patients present with a Chiari malformation type I. Other frequently reported causes include miscellaneous posterior fossa pathology, carotid or vertebrobasilar disease and cerebral aneurysms. Consequently, diagnostic neuroimaging is key in the diagnosis of cough-related headache and guides treatment. Besides primary and symptomatic cough headache, several other both primary and secondary headache disorders exist where coughing acts as a trigger or aggravator of headache symptomatology.
Zoonoses in pet birds: review and perspectives
Authors: Boseret Geraldine , Losson Bertrand , Mainil Jacques G , Thiry Etienne , Saegerman Claude
Published: May 2013

Pet birds are a not-so-well known veterinarian’s clientship fraction. Bought individually or in couples, as families often do (which is a lucrative business for pet shops or local breeders) or traded (sometimes illegally) for their very high genetic or exotic value, these birds, commonly canaries, parakeets or parrots, are regularly sold at high prices. These animals, however, are potential carriers and/or transmitters of zoonotic diseases. Some of them could have an important impact on human health, like chlamydophilosis, salmonellosis or even highly pathogenic avian influenza A H5N1. This review paper, although non exhaustive, aims at enlightening, by the description of several cases of bird-human transmission, the risks encountered by bird owners, including children. Public health consequences will be discussed and emphasis will be made on some vector-borne diseases, known to be emergent or which are underestimated, like those transmitted by the red mite Dermanyssus gallinae. Finally, biosecurity and hygiene, as well as prevention guidelines will be developed and perspectives proposed.
Chicken innate immune response to oral infection with Salmonella enterica serovar Enteritidis
Authors: Matulova Marta , Varmuzova Karolina , Sisak Frantisek , Havlickova Hana , Babak Vladimir , Stejskal Karel , Zdrahal Zbynek , Rychlik Ivan
Published: May 2013

The characterization of the immune response of chickens to Salmonella infection is usually limited to the quantification of expression of genes coding for cytokines, chemokines or antimicrobial peptides. However, processes occurring in the cecum of infected chickens are likely to be much more diverse. In this study we have therefore characterized the transcriptome and proteome in the chicken cecum after infection with Salmonella Enteritidis. Using a combination of 454 pyrosequencing, protein mass spectrometry and quantitative real-time PCR, we identified 48 down- and 56 up-regulated chicken genes after Salmonella Enteritidis infection. The most inducible gene was that coding for MMP7, exhibiting a 5952 fold induction 9 days post-infection. An induction of greater than 100 fold was observed for IgG, IRG1, SAA, ExFABP, IL-22, TRAP6, MRP126, IFNγ, iNOS, ES1, IL-1β, LYG2, IFIT5, IL-17, AVD, AH221 and SERPIN B. Since prostaglandin D2 synthase was upregulated and degrading hydroxyprostaglandin dehydrogenase was downregulated after the infection, prostaglandin must accumulate in the cecum of chickens infected with Salmonella Enteritidis. Finally, above mentioned signaling was dependent on the presence of a SPI1-encoded type III secretion system in Salmonella Enteritidis. The inflammation lasted for 2 weeks after which time the expression of the “inflammatory” genes returned back to basal levels and, instead, the expression of IgA and IgG increased. This points to an important role for immunoglobulins in the restoration of homeostasis in the cecum after infection.
Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus Glarea lozoyensis
Authors: Chen Li , Yue Qun , Zhang Xinyu , Xiang Meichun , Wang Chengshu , Li Shaojie , Che Yongsheng , Ortiz-López Francisco Javier , Bills Gerald F , Liu Xingzhong , An Zhiqiang
Published: May 2013

Background

The antifungal therapy caspofungin is a semi-synthetic derivative of pneumocandin B0, a lipohexapeptide produced by the fungusGlarea lozoyensis, and was the first member of the echinocandin class approved for human therapy. The nonribosomal peptide synthetase (NRPS)-polyketide synthases (PKS) gene cluster responsible for pneumocandin biosynthesis fromG. lozoyensishas not been elucidated to date. In this study, we report the elucidation of the pneumocandin biosynthetic gene cluster by whole genome sequencing of theG. lozoyensiswild-type strain ATCC 20868.

Results

The pneumocandin biosynthetic gene cluster contains a NRPS (GLNRPS4) and a PKS (GLPKS4) arranged in tandem, two cytochrome P450 monooxygenases, seven other modifying enzymes, and genes for L-homotyrosine biosynthesis, a component of the peptide core. Thus, the pneumocandin biosynthetic gene cluster is significantly more autonomous and organized than that of the recently characterized echinocandin B gene cluster. Disruption mutants of GLNRPS4 and GLPKS4 no longer produced the pneumocandins (A0and B0), and theΔglnrps4andΔglpks4mutants lost antifungal activity against the human pathogenic fungusCandida albicans. In addition to pneumocandins, theG. lozoyensisgenome encodes a rich repertoire of natural product-encoding genes including 24 PKSs, six NRPSs, five PKS-NRPS hybrids, two dimethylallyl tryptophan synthases, and 14 terpene synthases.

Conclusions

Characterization of the gene cluster provides a blueprint for engineering new pneumocandin derivatives with improved pharmacological properties. Whole genome estimation of the secondary metabolite-encoding genes fromG. lozoyensisprovides yet another example of the huge potential for drug discovery from natural products from the fungal kingdom.
Rectal forceps biopsy procedure in cystic fibrosis: technical aspects and patients perspective for clinical trials feasibility
Authors: Servidoni Maria F , Sousa Marisa , Vinagre Adriana M , Cardoso Silvia R , Ribeiro Maria A , Meirelles Luciana R , de Carvalho Rita B , Kunzelmann Karl , Ribeiro Antônio F , Ribeiro José D , Amaral Margarida D
Published: May 2013

Background

Measurements of CFTR function in rectal biopsies ex vivo have been used for diagnosis and prognosis of Cystic Fibrosis (CF) disease. Here, we aimed to evaluate this procedure regarding: i) viability of the rectal specimens obtained by biopsy forceps for ex vivo bioelectrical and biochemical laboratory analyses; and ii) overall assessment (comfort, invasiveness, pain, sedation requirement, etc.) of the rectal forceps biopsy procedure from the patients perspective to assess its feasibility as an outcome measure in clinical trials.

Methods

We compared three bowel preparation solutions (NaCl 0.9%, glycerol 12%, mannitol), and two biopsy forceps (standard and jumbo) in 580 rectal specimens from 132 individuals (CF and non-CF). Assessment of the overall rectal biopsy procedure (obtained by biopsy forceps) by patients was carried out by telephone surveys to 75 individuals who underwent the sigmoidoscopy procedure.

Results

Integrity and friability of the tissue specimens correlate with their transepithelial resistance (r = −0.438 and −0.305, respectively) and are influenced by the bowel preparation solution and biopsy forceps used, being NaCl and jumbo forceps the most compatible methods with the electrophysiological analysis. The great majority of the individuals (76%) did not report major discomfort due to the short procedure time (max 15 min) and considered it relatively painless (79%). Importantly, most (88%) accept repeating it at least for one more time and 53% for more than 4 times.

Conclusions

Obtaining rectal biopsies with a flexible endoscope and jumbo forceps after bowel preparation with NaCl solution is a safe procedure that can be adopted for both adults and children of any age, yielding viable specimens for CFTR bioelectrical/biochemical analyses. The procedure is well tolerated by patients, demonstrating its feasibility as an outcome measure in clinical trials.
Ocular inflammatory disease and ocular tuberculosis in a cohort of patients co-infected with HIV and multidrug-resistant tuberculosis in Mumbai, India: a cross-sectional study
Authors: Mehta Salil , Mansoor Homa , Khan Samsuddin , Saranchuk Peter , Isaakidis Petros
Published: May 2013

Background

The prevalence and the patterns of ocular inflammatory disease and ocular tuberculosis (TB) are largely undocumented among Multidrug Resistant TB (MDR-TB) patients co-infected with Human Immunodeficiency Virus (HIV) and on antituberculosis and antiretroviral therapy (ART).

Methods

Lilavati Hospital and Research Center and Médecins Sans Frontières (MSF) organized a cross-sectional ophthalmological evaluation of HIV/MDR-TB co-infected patients followed in an MSF-run HIV-clinic in Mumbai, India, which included measuring visual acuity, and slit lamp and dilated fundus examinations.

Results

Between February and April 2012, 47 HIV/MDR-TB co-infected patients (including three patients with extensively drug-resistant TB) were evaluated. Sixty-four per cent were male, mean age was 39 years (standard deviation: 8.7) and their median (IQR) CD4 count at the time of evaluation was 264 cells/μL (158–361). Thirteen patients (27%) had detectable levels of HIV viremia (>20 copies/ml). Overall, examination of the anterior segments was normal in 45/47 patients (96%). A dilated fundus examination revealed active ocular inflammatory disease in seven eyes of seven patients (15.5%, 95% Confidence Intervals (CI); 5.1-25.8%). ‘These included five eyes of five patients (10%) with choroidal tubercles, one eye of one patient (2%) with presumed tubercular chorioretinitis and one eye of one patient (2%) with evidence of presumed active CMV retinitis. Presumed ocular tuberculosis was thus seen in a total of six patients (12.7%, 95% CI; 3.2-22.2%). Two patients who had completed anti-TB treatment had active ocular inflammatory disease, in the form of choroidal tubercles (two eyes of two patients). Inactive scars were seen in three eyes of three patients (6%). Patients with extrapulmonary TB and patients <39 years old were at significantly higher risk of having ocular TB [Risk Ratio: 13.65 (95% CI: 2.4-78.5) and 6.38 (95% CI: 1.05-38.8) respectively].

Conclusions

Ocular inflammatory disease, mainly ocular tuberculosis, was common in a cohort of HIV/MDR-TB co-infected patients in Mumbai, India. Ophthalmological examination should be routinely considered in HIV patients diagnosed with or suspected to have MDR-TB, especially in those with extrapulmonary TB.
Determinants of inter birth interval among married women living in rural pastoral communities of southern Ethiopia: a case control study
Authors: Begna Zenebu , Assegid Sahilu , Kassahun Wondwosen , Gerbaba Mulusew
Published: May 2013

Background

Though birth interval has beneficial effects on health status of the mother and their children, it is affected by range of factors some of which are rooted in social and cultural norms and the reproductive behaviors of individual women. However, there was limited data showed the determinants of birth intervals in rural pastoral communities of South Ethiopia. Therefore, the study was aimed to assess the determinants of inter birth interval among women’s of child bearing age in Yaballo Woreda, Borena zone, Oromia Regional State, Ethiopia.

Methods

A community based unmatched case–control study with multi stage sampling technique was conducted from January to March 2012. Cases were women with two subsequent birth intervals of less than three years and controls were women with two subsequent birth intervals between three and above years. Simple random sampling technique was employed to select six hundred fifty two (326 cases and 326 controls) study subjects. All explanatory variables that were associated with the outcome variable (birth interval) during bivariate analysis were included in the final logistic model. Multivariable backward logistic regression when P values less than or equal to 0.05 and 95% CI were used to determine independent determinants for the outcome of interest.

Results

The median duration of birth interval was 31 & 40 months among cases and controls respectively. Variables such as number of children (AOR 3.73 95% CI: (1.50, 9.25), use of modern contraceptives (AOR 5.91 95% CI: (4.02, 8.69), mothers’ educational status (AOR 1.89 95% CI: (1.15, 3.37), and sex of the child (AOR 1.72 95% CI: (1.17, 2.52) were significantly associated with birth intervals.

Conclusions

Concerted efforts to encourage modern contraceptive use, women education, and breastfeeding should be made.
The roles of Notch1 expression in the migration of intrahepatic cholangiocarcinoma
Authors: Zhou Qi , Wang Yafeng , Peng Baogang , Liang Lijian , Li Jiaping
Published: May 2013

Background

Notch signaling, a critical pathway for tissue development, contributes to tumorigenesis in many tissues; however, the roles of Notch signaling in Intrahepatic Cholangiocarcinoma (ICC) remains unclear. In this study, we evaluated the expression and effects of Notch1 on cell migration in ICC.

Methods

Multiple cellular and molecular approaches were performed including gene transfection, siRNA transfection, RT-PCR, Western blotting, Rac activation assays and immunofluorescence.

Results

We found that Notch1 was up-regulated in ICC tissues and cell lines. The exogenous expression of Notch1 in glioma cells increased their migratory and invasive capacity. Similarly, the suppression of Notch1 expression inactivated Rac1 and inhibited ICC cell migration. Notch1 over expression induced an Epithelial-to-mesenchymal transition (EMT) phenotype that included enhanced expression of α-SMA and Vimentin, loss of E-cadherin expression, morphological changes and cytoskeletal reorganization in ICC cells.

Conclusion

Notch1 may induce a migratory effect in ICC by causing an epithelial-mesenchymal transition and activating Rac1 and could serve as a novel diagnostic and therapeutic target in patients with ICC.
Factors influencing the efficiency of generating genetically engineered pigs by nuclear transfer: multi-factorial analysis of a large data set
Authors: Kurome Mayuko , Geistlinger Ludwig , Kessler Barbara , Zakhartchenko Valeri , Klymiuk Nikolai , Wuensch Annegret , Richter Anne , Baehr Andrea , Kraehe Katrin , Burkhardt Katinka , Flisikowski Krzysztof , Flisikowska Tatiana , Merkl Claudia , Landmann Martina , Durkovic Marina , Tschukes Alexander , Kraner Simone , Schindelhauer Dirk , Petri Tobias , Kind Alexander , Nagashima Hiroshi , Schnieke Angelika , Zimmer Ralf , Wolf Eckhard
Published: May 2013

Background

Somatic cell nuclear transfer (SCNT) using genetically engineered donor cells is currently the most widely used strategy to generate tailored pig models for biomedical research. Although this approach facilitates a similar spectrum of genetic modifications as in rodent models, the outcome in terms of live cloned piglets is quite variable. In this study, we aimed at a comprehensive analysis of environmental and experimental factors that are substantially influencing the efficiency of generating genetically engineered pigs. Based on a considerably large data set from 274 SCNT experiments (in total 18,649 reconstructed embryos transferred into 193 recipients), performed over a period of three years, we assessed the relative contribution of season, type of genetic modification, donor cell source, number of cloning rounds, and pre-selection of cloned embryos for early development to the cloning efficiency.

Results

109 (56%) recipients became pregnant and 85 (78%) of them gave birth to offspring. Out of 318 cloned piglets, 243 (76%) were alive, but only 97 (40%) were clinically healthy and showed normal development. The proportion of stillborn piglets was 24% (75/318), and another 31% (100/318) of the cloned piglets died soon after birth. The overall cloning efficiency, defined as the number of offspring born per SCNT embryos transferred, including only recipients that delivered, was 3.95%. SCNT experiments performed during winter using fetal fibroblasts or kidney cells after additive gene transfer resulted in the highest number of live and healthy offspring, while two or more rounds of cloning and nuclear transfer experiments performed during summer decreased the number of healthy offspring.

Conclusion

Although the effects of individual factors may be different between various laboratories, our results and analysis strategy will help to identify and optimize the factors, which are most critical to cloning success in programs aiming at the generation of genetically engineered pig models.
X-ray irradiation promotes apoptosis of hippocampal neurons through up-regulation of Cdk5 and p25
Authors: Sun Ai-Min , Li Chuan-Gang , Han Yong-Qing , Liu Que-Ling , Xia Qiong , Yuan Ya-Wei
Published: May 2013

Background

Cranial radiation therapy has been used for the treatment of primary and metastatic brain tumors. A prominent feature of brain injury induced by the radiation therapy is hippocampal dysfunction, characterized by a decline in memory. Cdk5 plays an important role in memory formation. Abnormal Cdk5 activity is associated with neuronal apoptosis induced by neurotoxic stimuli. However, the roles of Cdk5 in hippocampal apoptosis in response to X-ray irradiation have not been explored.

Methods

The expression of Cdk5 activators, p35 and p25, in hippocampal neurons was tested in both in vivo animal and in vitro couture after X-ray irradiation.

Results

After X-ray irradiation at 20 Gy and 30 Gy in rats, the number of hippocampal neuronal pyknosis was increased, but the number of hippocampal neuron was decreased, in the hippocampal CA1 region of rats. In these animals undergone with X-ray irradiation, the expression of p35 was significantly down-regulated, but it was up-regulated in p25. These opposite expressions were also shown in the primary cultured hippocampal neurons with 30 Gy irradiation. The apoptosis induced by X-ray irradiation were significantly prevented by the pretreatment of Cdk5 inhibitor, roscovitine, in both in vivo and in vitro settings.

Conclusions

X-ray irradiation resulted in a hippocampal neuronal apoptosis through up-regulation of p25, the Cdk5 activator. Hyperactivity of Cdk5 was involved in the pathogenesis of X-ray irradiation-induced hippocampal neuronal apoptosis. Blockade of Cdk5 signal pathway effectively protected neurons from the irradiation-induced brain injury.
Expressions of candidate molecules in the human fallopian tube and chorionic villi of tubal pregnancy exposed to levonorgestrel emergency contraception
Authors: Huang Changxiao , Zhang Mei , Meng Chunxia , Shi Wei , Sun Lulu , Zhang Jian
Published: May 2013

Background

Cases of ectopic pregnancy (EP) following levonorgestrel (LNG) emergency contraception (EC) failure were reported, however, the effects of LNG on tubal microenvironment or chorionic villi in EP have not yet been documented.

Methods

Fifty-five women with tubal pregnancy were divided into two groups according to whether LNG-EC was administrated during the cycle of conception. The serum concentrations of beta-hCG, E2 and P were measured. The mRNA and protein expressions of estrogen and progesterone receptors, leukemia inhibitory factor, vascular endothelial growth factor, inducible nitric oxide synthase, and endocannabinoid receptor - CB1 in the ectopic implantation site and chorionic villi were examined.

Results

Compared to those unexposed to LNG-EC, women with tubal pregnancy exposed to LNG-EC during the cycle of conception had no statistically significances in the serum concentrations of beta-hCG, E2 P, nor in the pathological types of tubal pregnancy or the expressions of ER-alpha, PR, LIF, VEGF, iNOS and CB1.

Conclusions

The expressions of candidate molecules in the fallopian tube and chorionic villi were not altered by exposure to LNG-EC. A routine therapy with no additional intervention might thus be applied to tubal pregnancy exposed to LNG-EC.
Proteomic analysis of human spermatozoa proteins with oxidative stress
Authors: Sharma Rakesh , Agarwal Ashok , Mohanty Gayatri , Hamada Alaa J , Gopalan Banu , Willard Belinda , Yadav Satya , du Plessis Stefan
Published: May 2013

Background

Oxidative stress plays a key role in the etiology of male infertility. Significant alterations in the sperm proteome are associated with poor semen quality. The aim of the present study was to examine if elevated levels of reactive oxygen species cause an alteration in the proteomic profile of spermatozoa.

Methods

This prospective study consisted of 52 subjects: 32 infertile men and 20 normal donors. Seminal ejaculates were classified as ROS+ or ROS- and evaluated for their proteomic profile. Samples were pooled and subjected to LC-MS/MS analysis through in-solution digestion of proteins for peptide characterization. The expression profile of proteins present in human spermatozoa was examined using proteomic and bioinformatic analysis to elucidate the regulatory pathways of oxidative stress.

Results

Of the 74 proteins identified, 10 proteins with a 2-fold difference were overexpressed and 5 were underexpressed in the ROS+ group; energy metabolism and regulation, carbohydrate metabolic processes such as gluconeogenesis and glycolysis, protein modifications and oxidative stress regulation were some of the metabolic processes affected in ROS+ group.

Conclusions

We have identified proteins involved in a variety of functions associated with response and management of oxidative stress. In the present study we focused on proteins that showed a high degree of differential expression and thus, have a greater impact on the fertilizing potential of the spermatozoa. While proteomic analyses identified the potential biomarkers, further studies through Western Blot are necessary to validate the biomarker status of the proteins in pathological conditions.
Nanopore detection of DNA molecules in magnesium chloride solutions
Authors: Zhang Yin , Liu Lei , Sha Jingjie , Ni Zhonghua , Yi Hong , Chen Yunfei
Published: May 2013

High translocation speed of a DNA strand through a nanopore is a major bottleneck fornanopore detection of DNA molecules. Here, we choose MgCl2 electrolyte assalt solution to control DNA mobility. Experimental results demonstrate that theduration time for straight state translocation events in 1 M MgCl2solution is about 1.3 ms which is about three times longer than that for thesame DNA in 1 M KCl solution. This is because Mg2+ ions caneffectively reduce the surface charge density of the negative DNA strands and thenlead to the decrease of the DNA electrophoretic speed. It is also found that theMg2+ ions can induce the DNA molecules binding together and reduce theprobability of straight DNA translocation events. The nanopore with small diametercan break off the bound DNA strands and increase the occurrence probability ofstraight DNA translocation events.
Ethnobotanic importance of plants used in pigeon-breeding in Eastern Spain
Authors: Belda Antonio , Cortés Carolina , Peiró Victoriano
Published: May 2013

Background

The importance that birds of the Columbidae family have had throughout history is visible on the Mediterranean coast. Pigeon fancying is the art of breeding and training carrier pigeons and currently, several breeds exist. The sport of racing pigeons consists in covering a distance at maximum possible speed. However, pigeon breeding has another modality called “sport pigeon”, where several males follow a female. This study focusses on ethnobotanical knowledge of native and exotic plant species that are used for diet, breeding, stimulation, healing illnesses and staining the plumage of pigeons bred in captivity.

Methods

Using semi-structured interviews, we gathered information about the different plant species traditionally used for pigeon-breeding in the region of Valencia. Background material on remedies for bird illnesses was gathered from folk botanical references, local books and journals.The plant species were collected in the study area, then identified in the laboratory using dichotomous keys and vouchered in the ABH (Herbarium of Alicante University). We used Excel ® 2003 to perform a simple statistical analysis of the data collected.

Results

We collected 56 species of plants (and one variety) that included 29 botanical families. The total number of species was made up of 35 cultivated and 21 wild plants. The most common were Gramineae (14 species), Leguminosae (6 species), and Compositae (4 species).

Conclusions

Pigeon breeding is an immensely popular activity in Eastern Spain, and ethnobiological knowledge about breeding pigeons and caring for them is considerable. The names and traditional uses of plants depend on their geographical location, vernacular names serve as an intangible heritage. Feeding, environmental features, and genetic makeup of individuals are relevant aspects in the maintenance of avian health.