bluuebunny/crossref_metadata_2025 huggingface dataset:
Basophil Activation Test in Allergy: Time for an Update?
Authors: Chirumbolo Salvatore
Published: January 2012

A wide range of reported evidence in the literature has shown that the quantification of basophil activation by flow cytometry (basophil activation test, BAT) has proven to be a useful tool for the assessment of immediate-type responses to allergens mediated by IgE or other mechanisms in allergic patients. The usefulness of BAT in anaphylactic adverse reactions, late-onset allergy and immunotherapy follow-up has also been demonstrated. To date, most BAT studies reported in the literature involved the capture of basophils only with a fluorochrome-labeled anti-IgE antibody and application of CD63 upregulation in order to evaluate the basophil response to allergens. Many issues need to be addressed, such as optimizing the analytical performance of the test, checking preanalytical conditions, the selection of the flow cytometry best gating protocol, the introduction of new algorithms and parameters, the search for new activation markers and the introduction of anti-IgE controls. BAT is certainly a useful technique, also for isolated cases of hypersensitivity to various other compounds and drugs, and an update of its application is certainly an interesting topic to expand the debate on allergy diagnosis.
Geno2pheno[454]: A Web Server for the Prediction of HIV-1 Coreceptor Usage from Next-Generation Sequencing Data
Authors: Thielen Alexander , Lengauer Thomas
Published: January 2012

Inferring HIV-1 coreceptor usage from a genotype is becoming more and more important for the appropriate treatment of long-term patients. While results are already encouraging where standard bulk-nucleic acid sequencing methods are used, they are limited with respect to the detection of minor variants. In contrast, next-generation sequencing methods (ultradeep sequencing, pyrosequencing) are capable of sequencing virus quasispecies at very low quantities. However, as well as being very expensive, these methods generate vast amounts of data such that sequence analysis has to be automated by computer assistance. Here, we describe the geno2pheno[454] system which handles all processing and prediction steps involved in the prediction of coreceptor usage from massively parallel sequencing data. The system is split into a JAVA preprocessor which is run locally on the client side and a Web server which generates the prediction results. Predictions are based on the same prediction method as used in the geno2pheno[coreceptor] tool.
The XTrack System: Application and Advantage
Authors: Klimkait Thomas
Published: January 2012

XTrack, a rapid, cost-effective diagnostic HIV tropism system, yields predictive results and dissects virus mixtures. It is based on the duplexing of patient samples with selective DNA probes, combined with sequence-based analysis and replicative phenotyping for ambiguous samples.
Description of Two Commercially Available Assays for Genotyping of HIV-1
Authors: Stürmer Martin , Reinheimer Claudia
Published: January 2012

HIV-1 resistance testing is one important part in the diagnostics of antiretroviral treatment and is commonly done by genotyping. Currently, two systems are commercially available and, despite being far from easy to use, these have achieved a high degree of sophistication. Modifications of standard kit protocols might be necessary based on the clinical situation. Although resistance reports based on decision rules are a part of both systems, considerable knowledge and skills are nevertheless required by the user to establish useful clinical data out of detected resistance patterns. Both systems described here have their advantages and disadvantages; a decision for one or the other system needs to be based on individual requirements. The future might lie in so-called ‘next-generation sequencing’ systems based on pyrosequencing, which enable a high throughput and the detection of minor variants of less than 1%.
Prevalence and Prediction of Exercise-Induced Oxygen Desaturation in Patients with Chronic Obstructive Pulmonary Disease
Authors: van Gestel A.J.R. , Clarenbach C.F. , Stöwhas A.C. , Teschler S. , Russi E.W. , Teschler H. , Kohler M.
Published: January 2012

Background: Previous studies with small sample sizes reported contradicting findings as to whether pulmonary function tests can predict exercise-induced oxygen desaturation (EID). Objective: To evaluate whether forced expiratory volume in one second (FEV1), resting oxygen saturation (Spo2) and diffusion capacity for carbon monoxide (Dlco) are predictors of EID in chronic obstructive pulmonary disease (COPD). Methods: We measured FEV1, Dlco, Spo2 at rest and during a 6-min walking test as well as physical activity by an accelerometer. A drop in Spo2 of >4 to <90% was defined as EID. To evaluate associations between measures of lung function and EID univariate and multivariate analyses were used and positive/negative predictive values were calculated. Receiver operating characteristic curve analysis was performed to determine the most useful threshold in order to predict/exclude EID. Results: We included 154 patients with COPD (87 females). The mean FEV1 was 43.0% (19.2) predicted and the prevalence of EID was 61.7%. The only independent predictor of EID was FEV1 and the optimal cutoff value of FEV1 was at 50% predicted (area under ROC curve, 0.85; p < 0.001). The positive predictive value of a threshold of FEV1 <50% was 0.83 with a likelihood ratio of 3.03 and the negative predicting value of a threshold of FEV1 ≥80% was 1.0. The severity of EID was correlated with daily physical activity (r = –0.31, p = 0.008). Conclusions: EID is highly prevalent among patients with COPD and can be predicted by FEV1. EID seems to be associated with impaired daily physical activity which supports its clinical importance.
Diagnosis of Cardiovascular Disease in Patients with Chronic Kidney Disease
Authors: McCullough Peter A. , Assad Hadeel
Published: January 2012

The major forms of cardiovascular disease including coronary atherosclerosis, valvular disease, myocardial dysfunction, and arrhythmias are observed either alone or in combination in a large fraction of patients with chronic kidney disease (CKD). As CKD progresses, these cardiovascular conditions become more prevalent and severe. The clinical implications of combined heart and kidney disease include challenges in diagnosis and management. In addition, the terminal events in CKD commonly involve one of these four domains of cardiovascular disease. This paper will explore the issue of early diagnosis of heart disease in patients with CKD with the major goal being early intervention to lessen the impact of this comorbidity.
Novel Peritoneal Dialysis Solutions – What Are the Clinical Implications?
Authors: Jörres Achim
Published: January 2012

Novel low-glucose degradation products (GDP) peritoneal dialysis (PD) fluids have an improved biocompatibility profile as compared to standard fluids. Clinical studies suggest that their use may be associated with favorable clinical outcomes; however, large prospective randomized studies addressing clinical endpoints such as patient and technique survival are presently lacking. Nevertheless, as their only disadvantage is their cost, they are already being used as the standard treatment by many adult PD centers. This policy is also in line with the latest recommendations from the European Pediatric Dialysis Working Group which advises that conventional, single-chamber PD solutions should be replaced by PD solutions with reduced GDP content. The use of icodextrin, the glucose polymer PD solution, is recommended for patients with high or high-average peritoneal transport and/or ultrafiltration problems who otherwise would resort to hypertonic (3.86% glucose) exchanges.
Diagnosing Snowband Predictability Using a Multimodel Ensemble System
Authors: Novak David R. , Colle Brian A.
Published: January 2012

The forecast uncertainty of mesoscale snowband formation and evolution is compared using predictions from a 16-member multimodel ensemble at 12-km grid spacing for the 25 December 2002, 12 February 2006, and 14 February 2007 northeast U.S. snowstorms. Using these predictions, the case-to-case variability in the predictability of band formation and evolution is demonstrated. Feature-based uncertainty information is also presented as an example of what may be operationally feasible from postprocessing information from future short-range ensemble forecast systems. Additionally, the initial condition sensitivity of band location in each case is explored by contrasting the forecast evolutions of initial condition members with large differences in snowband positions. Considerable uncertainty in the occurrence, and especially timing and location, of band formation and subsequent evolution was found, even at forecast projections <24 h. The ensemble provided quantitative mesoscale band uncertainty information, and differentiated between high-predictability (14 February 2007) and low-predictability (12 February 2006) cases. Among the three cases, large (small) initial differences in the upper-level PV distribution and surface mean sea level pressure of the incipient cyclone were associated with large (small) differences in forecast snowband locations, suggesting that case-to-case differences in predictability may be related to the quality of the initial conditions. The complexity of the initial flow may also be a discriminator. Error growth was evident in each case, consistent with previous mesoscale predictability research, but predictability differences were not correlated to the degree of convection. Discussion of these results and future extensions of the work are presented.
Statistical modeling of water vapor transport through woven fabrics
Authors: Lee Seungsin , Obendorf S Kay
Published: January 2012

Water vapor transport through textile structures is complicated and governed by various factors, including fabric openness, fabric thickness, pore size, and intrinsic fiber properties. The objective of this study is to understand parameters that are critical in the moisture vapor transport through woven textiles and develop a predictive model that describes water vapor transport of woven fabrics using those parameters. Fifteen woven fabrics with various fabric thickness, weight, fabric construction, and staple fiber type were selected, and the water vapor transmission rate, fabric thickness, fabric count, weight, yarn number, yarn twist, yarn diameter, and pore size distribution were measured. Based on the mechanisms of water vapor transmission through porous textile materials, the fabric cover factor, solid volume fraction, yarn twist factor, and yarn packing factor were computed and used as possible predictor variables in the modeling. Moisture regains of fiber were obtained from literature and used as a possible predictor variable. Statistical analyses were performed to examine the relationship between these parameters and water vapor transmission. Statistical analyses revealed that fabric thickness, fabric cover factor, mean flow pore diameter of fabric, and moisture regain of fiber were significant parameters affecting water vapor transmission through woven fabrics. The adjusted R2 value for the final model selected was 0.97. Influence of yarn twist factor and yarn packing factor were shown to be insignificant at the 5% significance level for these experimental conditions.
The Use of Real‐Time Image Stabilization and Augmented Reality Eyewear in the Treatment of Oscillopsia
Authors: Pothier David D. , Hughes Cian , Dillon Wanda , Ranalli Paul J. , Rutka John A.
Published: January 2012

Objectives/Hypothesis

The symptom of oscillopsia in patients with bilateral vestibular loss (BVL) can be reduced as dynamic visual acuity (DVA), the reduction in visual acuity during head movement, is improved by using real‐time image stabilization, delivered by augmented reality eyewear.

Setting

Tertiary multidisciplinary neurotology clinic.

Study Design

Prospective experimental study.

Methods

Immersive virtual reality glasses used in combination with a compact digital video camera were used. A software algorithm was developed that used a center‐weighted Lucas‐Kanade optical flow method to stabilize video in real time. Six patients with BVL were tested for changes in DVA using the eyewear. The ability to read a Snellen chart during a 2‐Hz oscillating head rotation DVA test was measured.

Results

For combined scores of vertical and horizontal head rotations, the mean number of lines readable at rest was 7.86, which dropped to 2.77 with head movement (a combination of vertical and horizontal perturbations). This increased to a mean of 6.14 lines with the image stabilization software being activated. This difference was statistically significant (P<. 001).

Conclusion

This is the first successful attempt to improve dynamic visual acuity in patients with bilateral vestibular loss. Recent hardware upgrades are promising in improving these results even further.
Individual finger synchronized robot-assisted hand rehabilitation in subacute to chronic stroke: a prospective randomized clinical trial of efficacy
Authors: Hwang Chang Ho , Seong Jin Wan , Son Dae-Sik
Published: January 2012

Objective:

To evaluate individual finger synchronized robot-assisted hand rehabilitation in stroke patients.

Design:

Prospective parallel group randomized controlled clinical trial.

Subjects:

The study recruited patients who were ≥18 years old, more than three months post stroke, showed limited index finger movement and had weakened and impaired hand function. Patients with severe sensory loss, spasticity, apraxia, aphasia, disabling hand disease, impaired consciousness or depression were excluded.

Interventions:

Patients received either four weeks (20 sessions) of active robot-assisted intervention (the FTI (full-term intervention) group, 9 patients) or two weeks (10 sessions) of early passive therapy followed by two weeks (10 sessions) of active robot-assisted intervention (the HTI (half-term intervention) group, 8 patients). Patients underwent arm function assessments prior to therapy (baseline), and at 2, 4 and 8 weeks after starting therapy.

Results:

Compared to baseline, both the FTI and HTI groups showed improved results for the Jebsen Taylor test, the wrist and hand subportion of the Fugl-Meyer arm motor scale, active movement of the 2nd metacarpophalangeal joint, grasping, and pinching power ( P < 0.05 for all) at each time point (2, 4 and 8 weeks), with a greater degree of improvement for the FTI compared to the HTI group ( P < 0.05); for example, in Jebsen Taylor test (65.9 ± 36.5 vs. 46.4 ± 37.4) and wrist and hand subportion of the Fugl-Meyer arm motor scale (4.3 ± 1.9 vs. 3.4 ± 2.5) after eight weeks.

Conclusions:

A four-week rehabilitation using a novel robot that provides individual finger synchronization resulted in a dose-dependent improvement in hand function in subacute to chronic stroke patients.
Osteoblast viability on hydroxyapatite with well-adjusted submicron and micron surface roughness as monitored by the proliferation reagent WST-1
Authors: Holthaus Marzellus Große , Treccani Laura , Rezwan Kurosch
Published: January 2012

The impact of the cell surface roughness on titanium alloys used for biomedical implants has been extensively studied, whereas the dependency of human osteoblast viability on hydroxyapatite (HA) submicron and micron surface roughness has hitherto not yet been investigated in detail. Therefore, we investigate in this study the effect of HA substrates with different well-adjusted surface roughness on human osteoblast proliferation using the standard colorimetric reagent WST-1. By grinding, we obtained HA surfaces with six levels of well-defined surface roughness ranging from Sa = 3.36 µm down to 0.13 µm, resulting in hydrophilic contact angles from 11° to 27°. Energy dispersive X-ray spectroscopy, X-ray diffraction, and X-ray fluorescence measurements confirmed that neither grinding paper residues nor changes of the crystal structure were introduced to the HA substrates by the grinding process. By applying this simple surface treatment, we were able to isolate other effects from surface chemistry, crystal structure, and relative density. The changes of the osteoblast proliferation (WST-1 assay) on these different roughened HA surfaces after 7 days were found to be insignificant ( p > 0.05), evaluated by one-way analysis of variance and Tuckey’s Multiple Comparison Method. The results of this study show that all roughened HA surfaces, regardless of the microtopography, are biocompatible and allow osteoblast attachment, proliferation, and collagen type I production. The comparison with surface roughness used for standard Ti-based implants yielded that for HA no finishing process is necessary to ensure a sound human osteoblast cell proliferation in vitro.
Houttuyniae Herba protects rat primary cortical cells from Aβ25–35-induced neurotoxicity via regulation of calcium influx and mitochondria-mediated apoptosis
Authors: Park H , Oh MS
Published: January 2012

Amyloid beta (Aβ) fibrils are believed to play a major role in the pathogenesis of Alzheimer’s disease. Although the mechanisms underlying Aβ toxicity remain largely unknown, Aβ fibrils disrupt calcium homeostasis and generate free radicals, resulting in oxidative stress, mitochondrial dysfunction, and apoptotic cell death. Houttuyniae Herba, the aerial part of Houttuynia cordata Thunb. (Saururaceae), is a commonly used herb in traditional Asian medicine. It has been reported to have various bioactivities, including antioxidant effects. In the present study, we investigated the protective effect of standardised Houttuyniae Herba water extract (HCW) against Aβ25–35-induced neurotoxicity and its possible mechanisms in rat primary cortical cells. Pretreatment with HCW attenuated the cell damage caused by 8 μM Aβ25–35 exposure, as evidenced by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, a lactate dehydrogenase assay, and microtubule-associated protein 2 immunostaining. Moreover, HCW inhibited the Aβ25–35-induced elevation of the intracellular calcium level, reactive oxygen species overproduction, mitochondrial membrane potential disruption, and caspase 3 activation. These results indicate that HCW protects rat primary cortical neurons against Aβ25–35-induced toxicity via the regulation of calcium and the inhibition of mitochondria-mediated apoptosis.
Enhanced active constrained layer damping (ACLD) treatment using stand-off-layer: robust controllers design, experimental implementation and comparison
Authors: Kumar Rajiv
Published: January 2012

It is a well known fact that system parameters of flexible structures keep on changing because of several reasons. Ordinary controllers lose their effectiveness in changed situations and do not guarantee the stability of the closed loop (CL) system. However, controllers designed based on robust control theory not only maintain the CL stability of the perturbed system for a large variation in system parameters but also maintain best performance. In this work, [Formula: see text] optimization based controllers are designed and implemented experimentally on a flexible beam with active constrained layer damping treatment. It is observed that [Formula: see text] loop shaping design procedure based controllers outperform linear quadratic Gaussian and standard [Formula: see text]controllers both in terms of robust stability and robust performance. Relative merits and demerits of the controllers designed using [Formula: see text]- synthesis technique are also discussed. It has also been observed that time domain results also explain some of the important facts. Certain time domain parameters of the CL system prove the relative superiority of these controllers in terms of control energy utilization and robust performance.
Exploring how and why people use visualizations in casual contexts: Modeling user goals and regulated motivations
Authors: Sprague David , Tory Melanie
Published: January 2012

We present an artifact study that explores how people examine visual representations of data in non-work contexts, resulting in a proposed Promoter–Inhibitor Motivation Model of visualization use in casual contexts. We propose that user goals direct visualization use tasks, but the strength of user motivation is modified by promoting and inhibiting factors. Based on the duration and frequency of use for reported artifacts, we hypothesize that artifact use patterns depend on how promoters and inhibitors change over time, and we propose a six-stage model of artifact use. We hypothesize that the differences in how these artifacts were used ultimately reveals how promoters and inhibitors can be manipulated to promote frequent and long-duration visualization use. This model provides a cognitive framework for visualization designers and suggests new research directions.
Spot weldability of TRIP assisted steels with high carbon and aluminium contents
Authors: Jung G S , Lee K Y , Lee J B , Bhadeshia H K D H , Suh D-W
Published: January 2012

We examine here the spot welding characteristics of transformation induced plasticity assisted steels, which contain δ-ferrite as a consequence of their aluminium concentrations of 3·5 or 5·6 wt-% and which also have high carbon contents of 0·3 or 0·4 wt-% when compared with conventional automotive steels. The resistance spot welds are tested in both shear and cross-tensile tests in order to determine the so called ductility ratio, which is a parameter associated with the fitness of such welds for automotive applications. With an increase in the δ-ferrite fraction from 0·19 to 0·5, the hardness variation across the weld and heat affected zone is decreased approximately from 400 to 150 HV. It seems that the presence of stable δ-ferrite is helpful in reducing hardness variations and in achieving a significant ductility ratio of 0·39.
Numerical simulation of shielding gas behaviour in tungsten inert gas welding of titanium plate
Authors: Wada Y , Inoue S , Tsukamoto H , Yamaguchi T , Nishio K
Published: January 2012

To minimise the volume of argon required for on-site tungsten inert gas welding of titanium plate, the authors investigated the behaviour of argon flow in a trailing–shielding box by means of computational fluid dynamics (CFD) simulations. In this study, a solid rectangular shielding box consisting of 9·5×105 tetrahedral elements was modelled. Then, argon flow was simulated for two shielding parameters, namely, the argon supply rate and the gap between the box and the floor. In the experiment, the relation between the oxygen content in the shielding box and the shielding parameters was studied. The experimental results show that the simulation model used in the CFD simulations can predict the behaviour of argon. It is concluded that the simulation model is useful for improving the structure of the shielding box.
Banding in copper friction stir weld
Authors: Savolainen K , Saukkonen T , Hänninen H
Published: January 2012

Formation and microstructure of banding in a copper friction stir weld was studied using scanning electron microscopy, electron backscatter diffraction, and nanoindentation. Unlike in aluminium, banding only appears in ‘cold’ friction stir welding (FSW) welds of copper. Banding is formed by layers of small and large grains. It was noticed that higher local misorientations and small grain size correlate in the welds. Owing to differences in the restoration processes of copper and aluminium, texture changes are not visible in copper even though they are in aluminium. Texture of copper FSW welds is weak and independent of the grain structure of the base material, because in the steady state dynamic recrystallisation, the restoration process of copper, the grain structure is mainly dependent of the processing parameters. The hardness differences between the small and large grains are small.
Targeting of GSK3β promotes imatinib-mediated apoptosis in quiescent CD34+ chronic myeloid leukemia progenitors, preserving normal stem cells
Authors: Reddiconto Giovanni , Toto Claudia , Palamà Ilaria , De Leo Simone , de Luca Emanuela , De Matteis Serena , Dini Luciana , Passerini Carlo Gambacorti , Di Renzo Nicola , Maffia Michele , Coluccia Addolorata Maria Luce
Published: January 2012

The targeting of BCR-ABL, a hybrid oncogenic tyrosine (Y) kinase, does not eradicate chronic myeloid leukemia (CML)–initiating cells. Activation of β-catenin was linked to CML leukemogenesis and drug resistance through its BCR-ABL–dependent Y phosphorylation and impaired binding to GSK3β (glycogen synthase kinase 3β). Herein, we show that GSK3β is constitutively Y216 phospho-activated and predominantly relocated to the cytoplasm in primary CML stem/progenitor cells compared with its balanced active/inactive levels and cytosolic/nuclear distribution in normal cells. Under cytokine support, persistent GSK3β activity and its altered subcellular localization were correlated with BCR-ABL–dependent and –independent activation of MAPK and p60-SRC/GSK3β complex formation. Specifically, GSK3β activity and nuclear import were increased by imatinib mesylate (IM), a selective ABL inhibitor, but prevented by dasatinib that targets both BCR-ABL– and cytokine-dependent MAPK/p60-SRC activity. SB216763, a specific GSK3 inhibitor, promoted an almost complete suppression of primary CML stem/progenitor cells when combined with IM, but not dasatinib, while sparing bcr-abl–negative cells. Our data indicate that GSK3 inhibition acts to prime a pro-differentiative/apoptotic transcription program in the nucleus of IM-treated CML cells by affecting the β-catenin, cyclinD1, C-EBPα, ATF5, mTOR, and p27 levels. In conclusion, our data gain new insight in CML biology, indicating that GSK3 inhibitors may be of therapeutic value in selectively targeting leukemia-initiating cells in combination with IM but not dasatinib.
Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma
Authors: Santo Loredana , Hideshima Teru , Kung Andrew L. , Tseng Jen-Chieh , Tamang David , Yang Min , Jarpe Matthew , van Duzer John H. , Mazitschek Ralph , Ogier Walter C. , Cirstea Diana , Rodig Scott , Eda Homare , Scullen Tyler , Canavese Miriam , Bradner James , Anderson Kenneth C. , Jones Simon S. , Raje Noopur
Published: January 2012

Histone deacetylase (HDAC) enzymatic activity has been linked to the transcription of DNA in cancers including multiple myeloma (MM). Therefore, HDAC inhibitors used alone and in combination are being actively studied as novel therapies in MM. In the present study, we investigated the preclinical activity of ACY-1215, an HDAC6-selective inhibitor, alone and in combination with bortezomib in MM. Low doses of ACY-1215 combined with bortezomib triggered synergistic anti-MM activity, resulting in protracted endoplasmic reticulum stress and apoptosis via activation of caspase-3, caspase-8, and caspase-9 and poly (ADP) ribosome polymerase. In vivo, the anti-MM activity of ACY-1215 in combination with bortezomib was confirmed using 2 different xenograft SCID mouse models: human MM injected subcutaneously (the plasmacytoma model) and luciferase-expressing human MM injected intravenously (the disseminated MM model). Tumor growth was significantly delayed and overall survival was significantly prolonged in animals treated with the combination therapy. Pharmacokinetic data showed peak plasma levels of ACY-1215 at 4 hours after treatment coincident with an increase in acetylated α-tubulin, a marker of HDAC6 inhibition, by immunohistochemistry and Western blot analysis. These studies provide preclinical rationale for acetylated α-tubulin use as a pharmacodynamic biomarker in future clinical trials.
Benchmarks for flexible and rigid transcription factor-DNA docking
Authors: Kim RyangGuk , Corona Rosario I , Hong Bo , Guo Jun-tao
Published: January 2012

Background

Structural insight from transcription factor-DNA (TF-DNA) complexes is of paramount importance to our understanding of the affinity and specificity of TF-DNA interaction, and to the development of structure-based prediction of TF binding sites. Yet the majority of the TF-DNA complexes remain unsolved despite the considerable experimental efforts being made. Computational docking represents a promising alternative to bridge the gap. To facilitate the study of TF-DNA docking, carefully designed benchmarks are needed for performance evaluation and identification of the strengths and weaknesses of docking algorithms.

Results

We constructed two benchmarks for flexible and rigid TF-DNA docking respectively using a unified non-redundant set of 38 test cases. The test cases encompass diverse fold families and are classified into easy and hard groups with respect to the degrees of difficulty in TF-DNA docking. The major parameters used to classify expected docking difficulty in flexible docking are the conformational differences between bound and unbound TFs and the interaction strength between TFs and DNA. For rigid docking in which the starting structure is a bound TF conformation, only interaction strength is considered.

Conclusions

We believe these benchmarks are important for the development of better interaction potentials and TF-DNA docking algorithms, which bears important implications to structure-based prediction of transcription factor binding sites and drug design.
Geographic Information System and tools of spatial analysis in a pneumococcal vaccine trial
Authors: Tanskanen Antti , Nillos Leilani T , Lehtinen Antti , Nohynek Hanna , Sanvictores Diozele Hazel M , Simões Eric AF , Tallo Veronica L , Lucero Marilla G ,   ARIVAC Consortium
Published: January 2012

Background

The goal of this Geographic Information System (GIS) study was to obtain accurate information on the locations of study subjects, road network and services for research purposes so that the clinical outcomes of interest (e.g., vaccine efficacy, burden of disease, nasopharyngeal colonization and its reduction) could be linked and analyzed at a distance from health centers, hospitals, doctors and other important services. The information on locations can be used to investigate more accurate crowdedness, herd immunity and/or transmission patterns.

Method

A randomized, placebo-controlled, double-blind trial of an 11-valent pneumococcal conjugate vaccine (11PCV) was conducted in Bohol Province in central Philippines, from July 2000 to December 2004. We collected the information on the geographic location of the households (N = 13,208) of study subjects. We also collected a total of 1982 locations of health and other services in the six municipalities and a comprehensive GIS data over the road network in the area.

Results

We calculated the numbers of other study subjects (vaccine and placebo recipients, respectively) within the neighborhood of each study subject. We calculated distances to different services and identified the subjects sharing the same services (calculated by distance). This article shows how to collect a complete GIS data set for human to human transmitted vaccine study in developing country settings in an efficient and economical way.

Conclusions

The collection of geographic locations in intervention trials should become a routine task. The results of public health research may highly depend on spatial relationships among the study subjects and between the study subjects and the environment, both natural and infrastructural.

Trial registration number

ISRCTN: ISRCTN62323832
Interleukin-34 produced by human fibroblast-like synovial cells in rheumatoid arthritis supports osteoclastogenesis
Authors: Hwang Seung-Jun , Choi Bongkun , Kang Soon-Suk , Chang Jae-Ho , Kim Yong-Gil , Chung Yeon-Ho , Sohn Dong Hyun , So Min Wook , Lee Chang-Keun , Robinson William H , Chang Eun-Ju
Published: January 2012

Introduction

Interleukin-34 (IL-34) is a recently defined cytokine, showing a functional overlap with macrophage colony stimulating factor (M-CSF). This study was undertaken to address the expression of IL-34 in rheumatoid arthritis (RA) patients and to investigate its regulation and pathogenic role in RA.

Methods

IL-34 levels were determined in the RA synovium, synovial fluid (SF) and fibroblast-like synovial cells (FLS) by immunohistochemistry, real-time PCR, enzyme-linked immunosorbent assay and immunoblotting. RA activity was assessed using Disease Activity Score 28 (DAS28) activity in the plasma collected at baseline and one year after treatment. Conditioned media (CM) were prepared from RA FLS culture with tumor necrosis factor alpha (TNFα) for 24 hours and used for functional assay.

Results

IL-34 was expressed in the synovium, SF, and FLS from RA patients. The production of IL-34 in FLS was up-regulated by TNFα in RA samples compared with osteoarthritis (OA) patients. Importantly, the preferential induction of IL-34 rather than M-CSF by TNFα in RAFLS was mediated by the transcription factor nuclear factor kappa B (NF-κB) and activation of c-Jun N-terminal kinase (JNK). IL-34 elevation in plasma from RA patients was decreased after the administration of disease-modifying anti-rheumatic drugs (DMARDs) in accordance with a decrease in DAS28. CM from RAFLS cultured with TNFα promoted chemotactic migration of human peripheral blood mononuclear cells (PBMCs) and subsequent osteoclast (OC) formation, effects that were attenuated by an anti-IL-34 antibody.

Conclusions

These data provide novel information about the production of IL-34 in RA FLS and indicate that IL-34 is an additional osteoclastogenic factor regulated by TNFα in RA, suggesting a discrete role of IL-34 in inflammatory RA diseases.
A novel p38-MAPK signaling axis modulates neutrophil biology in head and neck cancer
Authors: Dumitru Claudia A , Fechner Maren K , Hoffmann Thomas K , Lang Stephan , Brandau Sven
Published: January 2012

Neutrophils are emerging as important mediators in cancer progression. Recent studies associated neutrophils with poor clinical outcome of HNC patients and showed that HNC induces recruitment, survival, and release of proinflammatory factors by neutrophils in vitro. The molecular mechanisms through which HNC and other cancers modulate neutrophil biology are currently unknown. To explore these mechanisms, we used an in vitro system that models the interaction between human HNC cells and neutrophils or neutrophilic-differentiated HL-60 cells, respectively. We show that HNC-derived factors activate p38-MAPK in neutrophils, which partly promotes neutrophil survival, but not neutrophil recruitment and motility. Most importantly, HNC-induced p38-MAPK activation strongly stimulates the release of CCL4, CXCL8, and MMP9 by neutrophils. We identify CREB and interestingly, p27 phosphorylated at T198 as downstream members of the HNC-induced p38-MAPK signaling cascade. Using siRNA technology, we demonstrate that p27 and CREB mediate the release of CCL4 and CXCL8 and that CREB, additionally, mediates the release of MMP9. These data unravel novel molecular mechanisms involved in regulation of neutrophil proinflammatory functions. Our studies on human HNC tissues indicate that tumor-infiltrating neutrophils might be a major source of CCL4 and particularly, MMP9 in cancer patients. Thus, our findings provide novel, mechanistic insights relevant for the pathophysiology of HNC and possibly, other types of cancer as well.
A walking intervention for postmenopausal women using mobile phones and interactive voice response
Authors: David Prabu , Buckworth Janet , Pennell Michael L , Katz Mira L , DeGraffinreid Cecilia R , Paskett Electra D
Published: January 2012

We conducted a feasibility study of a 12-week walking intervention administered through an Interactive Voice Response (IVR) system and mobile phones. We also examined the added benefit of a human coach. Post-menopausal women ( n = 71) were given a daily-steps goal, which they monitored using a pedometer. Each day, they answered an automated call from the IVR system to their mobile phone and provided assessments of walking goals and mood. Every evening, they called the IVR system to report their steps, answered a brief questionnaire and received a message with a helpful hint. Participants took less time to complete a one-mile walk after the intervention, compared to baseline (0.77 min, SE = 0.22, P < 0.001). In addition, a significant loss in body weight (0.93 kg, SE = 0.31) and body-mass index (0.28 kg/m2, SE = 0.11) were observed. The key psychometric measures of exercise goal setting (0.67 units, SE = 0.12) and exercise planning (0.48 units, SE = 0.09) also improved from baseline (both P < 0.001). However, results in the coach and no-coach conditions were not significantly different. The study suggests that mobile phones can be used to deliver an effective, low-cost walking intervention, irrespective of the addition of a human coach.
Remote CT reading using an ultramobile PC and web-based remote viewing over a wireless network
Authors: Choi Hyuk Joong , Lee Jeong Hun , Kang Bo Seung
Published: January 2012

We developed a new type of mobile teleradiology system using an ultramobile PC (UMPC) for web-based remote viewing over a wireless network. We assessed the diagnostic performance of this system for abdominal CT interpretation. Performance was compared with an emergency department clinical monitor using a DICOM viewer. A total of 100 abdominal CT examinations were presented to four observers. There were 56 examinations showing appendicitis and 44 which were normal. The observers viewed the images using a UMPC display and an LCD monitor and rated each examination on a five-point scale. Receiver operating characteristics (ROC) analysis was used to test for differences. The sensitivity and specificities of all observers were similarly high. The average area under the ROC curve for readings performed on the UMPC and the LCD monitor was 0.959 and 0.976, respectively. There were no significant differences between the two display systems for interpreting abdominal CTs. The web-based mobile teleradiology system appears to be feasible for reading abdominal CTs for diagnosing appendicitis and may be valuable in emergency teleconsultation.
The utility of Y-STR profiling in four-, six- and eight-day postcoital vaginal swabs
Authors: Quarino Lawrence , Kishbaugh Janine
Published: January 2012

Y-STR profiles using the Promega PowerPlex® Y system were attempted on multiple vaginal swabs collected at four, six and eight days after intercourse from female partners of 11 couples. At four days postcoitus, full composite profiles (where swabs yielded confirmed alleles at all 11 loci) were obtained for five of the 11 couples and 78% of all possible alleles summed for all couples were confirmed (able to be duplicated in different swabs). Results for composite profiles for all couples taken at six days after intercourse showed that 53% of all alleles summed for all couples were confirmed. Only one couple yielded a full composite profile at six days after intercourse. Composite profiles from swabs taken at eight days after intercourse for all couples confirmed only 44% of all possible alleles summed for all couples. At eight days postcoitus, no couple yielded a full composite profile and the largest number of confirmed alleles for any couple was eight. However, one of 44 individual swabs taken from all couples combined at eight days postcoitus yielded a 10-locus profile. Composite partial profiles from the eight-day postcoital set with confirmed results at a minimum of five loci (8 of 11 couples) yielded haplotype frequencies from 0.000323 to 0.125862 using the Y chromosome haplotype reference database, suggesting that meaningful Y-STR information can still be obtained at much extended postcoital intervals.
Drop foot, a rare complication following Müller's phlebectomy
Authors: Otters E F M , van Neer P A F A
Published: January 2012

In this article we present a case of a temporary foot drop after ambulatory phlebectomy. The temporary nerve blockage was caused by anaesthetic infiltration. In treating varicose veins using the technique of Müller, care must be taken for transient nerve palsies.
Doing Nothing: Adults With Disabilities With No Daily Activities and Their Siblings
Authors: Taylor Julie Lounds , Hodapp Robert M
Published: January 2012

A significant concern of parents and professionals is that adults with intellectual and developmental disabilities will go without regular educational–vocational activities. The authors examined predictors of such inactivity in individuals with intellectual and developmental disabilities, as well as how inactivity related to their sibling's well-being and the sibling relationship. Participants included 796 siblings of adults with intellectual and developmental disabilities who responded to a web-based survey. Nearly 13% of adults with intellectual and developmental disabilities were without daytime activities; these adults had more emotional–behavioral and health problems, were more underserved by the formal service system, and had parents who were less able to provide care. Although siblings of adults without activities reported more depressive symptoms, worse health, and less close sibling relationships, inactivity no longer predicted these problems after controlling for characteristics that predisposed adults with intellectual and developmental disabilities to have no activities.
Absence of the Basement Membrane Component Nidogen 2, but Not of Nidogen 1, Results in Increased Lung Metastasis in Mice
Authors: Mokkapati Sharada , Bechtel Manuela , Reibetanz Marion , Miosge Nicolai , Nischt Roswitha
Published: January 2012

Nidogen 1 and 2 are ubiquitous basement membrane (BM) components. They show a divergent expression pattern in certain adult tissues with a prominent localization of nidogen 2 in blood vessel BMs. Deletion of either nidogen 1 or 2 in mice had no effect on BM formation, suggesting complementary functions. However, studies in these mice revealed isoform-specific functions with nidogen 1–deficient mice showing neurological abnormalities and wound-healing defects not seen in the absence of nidogen 2. To investigate this further nidogen 1– or 2–deficient mice were intravenously injected with B16 murine melanoma cells, and lung metastasis was analyzed. The authors could show that loss of nidogen 2, but not of nidogen 1, significantly promotes lung metastasis of melanoma cells. Histological and ultrastructural analysis of nidogen 1– and 2–deficient lungs did not reveal differences in morphology and ultrastructure of BMs, including vessel BMs. Furthermore, deposition and distribution of the major BM components were indistinguishable between the two mouse strains. Taken together, these results suggest that absence of nidogen 2 might result in subtle changes of endothelial BMs in the lung, which would allow faster passage of tumor cells through these BMs, leading to a higher metastasis rate and more larger tumors.
Detection of Disease-associated Prion Protein in the Optic Nerve and the Adrenal Gland of Cattle with Bovine Spongiform Encephalopathy by Using Highly Sensitive Immunolabeling Procedures
Authors: Okada Hiroyuki , Iwamaru Yoshifumi , Fukuda Shigeo , Yokoyama Takashi , Mohri Shirou
Published: January 2012

A sensitive immunohistochemical procedure, the tyramide signal amplification (TSA) system, was applied to detect the localization of immunolabeled disease-associated prion protein (PrPSc) in cattle affected with bovine spongiform encephalopathy (BSE). In this procedure, immunolabeling could be visualized in the optic nerve and the adrenal medulla. In the optic nerve, the dual immunofluorescent technique showed that the granular PrPSc was occasionally detected in the astrocytes, microglia, and myelin sheath adjacent to the axon. Clustered PrPSc was also scattered in association with microglial cells and astrocytes of the optic nerve. In the adrenal gland, PrPSc immunolabeling was confined within the sympathetic nerve fibers and endings. The results suggest that (1) PrPSc might centrifugally spread within and between glial cells and/or the non-axonal (also known as ad-axonal) region of nerve fibers, rather than the axonal and/or extracellular space pathway in the optic nerve, and (2) the sympathetic innervations might be important for the trafficking of BSE agent in the adrenal glands of cattle. This study also suggests that tyramide-based immunochemical analysis should be performed to detect immunolabeled PrPSc in the extracerebral tissues of BSE-affected cattle.
Mesoscale Simulation of the Structure of Star Acrylated Poly(ethylene glycol-co-lactide) Hydrogels
Authors: Moeinzadeh Seyed Sina , Jabbari Esmaiel
Published: January 2012

In this work the microstructures of star acrylated poly(ethylene glycol-co-lactide) (SPELA) with different LA:EG ratios in the aqueous solution have been simulated via Dissipative Particle Dynamics (DPD) approach at the mesoscale. The system components were coarse-grained into different beads (set of atoms) which moved according to the Newton’s equations of motion integrated via a modified Velocity-Verlet algorithm. The force acting on each bead, in a specific cutoff distance (rc), was divided into a conservative force (FC), random force (FR), dissipative force (FD), bond force (FS) and bond angle force (FE). The repulsion parameters of the conservative force (αij) were calculated from the solubility parameter of the beads, each of which were extracted from an atomistic molecular dynamics simulation (MD). Simulations showed the formation of micelles with lactide and acrylate beads occupied the core and hydrophilic ethylene oxide segments extending through the water to form the corona. The micelles showed an increasing trend in size and decreasing trend in number density with increase in LA:EG ratio. Results showed that the acrylate density decreased from the center of the micelles to the core surface although the overall amount of acrylates increased due to the increase in volume. Furthermore, the running integration number of acrylate-water beads showed decreasing accessibility of acrylates to water with increasing PLA volume fraction.
3D Printing Fumarate Based Polymers
Authors: Cicotte Kirsten N. , Hedberg-Dirk Elizabeth L. , Dirk Shawn M.
Published: January 2012

Recently, an inexpensive 3D lithography technique was developed by Professor Nicholas Fang at the University of Illinois where a projector is used in combination with a Microsoft® PowerPoint presentation to expose the liquid negative-tone photoresist 1,6-hexanediol diacrylate in a layer-by-layer fashion. Where Professor Fang initially used this method as a teaching tool, we have used the inexpensive 3D printing technique to create 3D structures of fumarate based polymers. This class of polymers are liquids at room temperature which makes them ideal for the projector based lithography technique when used in combination with the photoinitiator bisphenyl(2,4,6-trimethylbenzoyl)-phosphine oxide (BAPO). Furthermore, the fumarate based materials are biocompatible and are suitable candidates for tissue engineering applications.
O corpo na escola: mapeamentos necessários
Authors: Farah Marisa Helena Silva
Published: January 2012

Este estudo propõe um mapeamento do corpo na escola, na tentativa de possibilitar aos educadores iniciantes uma construção do olhar para o aluno com seu corpo, bem como estimular o educador a se situar com seu corpo nesse contexto. Partindo da análise de dois eixos interdependentes: (1) a concepção de sujeito-corpo e (2) espaços e tempos do corpo na escola, busca-se contribuir para a discussão educacional, expondo como o currículo, a didática e a avaliação, entre outros elementos, podem sinalizar as considerações dadas ao corpo. O estudo conclui mostrando o parodoxo representado pelos mesmos elementos, quando problematizados por meio das relações de poder.