bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface Potential Distribution in an Indentation‐ Pre‐Cracked BaTiO3 Single Crystal
Authors: Sun X. , Su Y. J. , Gao K. W. , Guo L. Q. , Qiao L. J. , Chu W. Y. , Zhang Tong‐Yi
Published: June 2011

This article presents surface electric potential distributions, measured by Kelvin Probe Force Microscopy, on the (001) surface in an indentation‐pre‐cracked BaTiO3 single crystal with and without applied electric field. The results show that cracks are higher potential regions in comparison to other regions. The higher surface potential is induced by the crack itself in air at room temperature and an applied in‐plane electric field cannot change the major feature of the potential distribution across the crack.
Sequential use of human‐derived medium supplements favours cardiovascular tissue engineering
Authors: Vis Paul W. Riem , Sluijter Joost P. G. , Soekhradj‐Soechit R. Sarita , van Herwerden Lex A. , Kluin Jolanda , Bouten Carlijn V. C.
Published: June 2011

For clinical application of tissue engineering strategies, the use of animal‐derived serum in culture medium is not recommended, because it can evoke immune responses in patients. We previously observed that human platelet‐lysate (PL) is favourable for cell expansion, but generates weaker tissue as compared to culture in foetal bovine serum (FBS). We investigated if human serum (HS) is a better human supplement to increase tissue strength. Cells were isolated from venous grafts of 10 patients and expanded in media supplemented with PL or HS, to determine proliferation rates and expression of genes related to collagen production and maturation. Zymography was used to assess protease expression. Collagen contraction assays were used as a two‐dimensional (2D) model for matrix contraction. As a prove of principle, 3D tissue culture and tensile testing was performed for two patients, to determine tissue strength. Cell proliferation was lower in HS‐supplemented medium than in PL medium. The HS cells produced less active matrix metallo‐proteinase 2 (MMP2) and showed increased matrix contraction as indicated by gel contraction assays and 3D‐tissue culture. Tensile testing showed increased strength for tissues cultured in HS when compared to PL. This effect was more pronounced if cells were sequentially cultured in PL, followed by tissue culture in HS. These data suggest that sequential use of PL and HS as substitutes for FBS in culture medium for cardiovascular tissue engineering results in improved cell proliferation and tissue mechanical properties, as compared to use of PL or HS apart.
Role of Slug transcription factor in human mesenchymal stem cells
Authors: Torreggiani Elena , Lisignoli Gina , Manferdini Cristina , Lambertini Elisabetta , Penolazzi Letizia , Vecchiatini Renata , Gabusi Elena , Chieco Pasquale , Facchini Andrea , Gambari Roberto , Piva Roberta
Published: June 2011

The pathways that control mesenchymal stem cells (MSCs) differentiation are not well understood, and although some of the involved transcription factors (TFs) have been characterized, the role of others remains unclear. We used human MSCs from tibial plateau (TP) trabecular bone, iliac crest (IC) bone marrow and Wharton’s jelly (WJ) umbilical cord demonstrating a variability in their mineral matrix deposition, and in the expression levels of TFs including Runx2, Sox9, Sox5, Sox6, STAT1 and Slug, all involved in the control of osteochondroprogenitors differentiation program. Because we reasoned that the basal expression level of some TFs with crucial role in the control of MSC fate may be correlated with osteogenic potential, we considered the possibility to affect the hMSCs behaviour by using gene silencing approach without exposing cells to induction media. In this study we found that Slug‐silenced cells changed in morphology, decreased in their migration ability, increased Sox9 and Sox5 and decreased Sox6 and STAT1 expression. On the contrary, the effect of Slug depletion on Runx2 was influenced by cell type. Interestingly, we demonstrated a direct in vivo regulatory action of Slug by chromatin immunoprecipitation, showing a specific recruitment of this TF in the promoter of Runx2 and Sox9 genes. As a whole, our findings have important potential implication on bone tissue engineering applications, reinforcing the concept that manipulation of specific TF expression levels may elucidate MSC biology and the molecular mechanisms, which promote osteogenic differentiation.
Angiotensin II receptor type 1 blockade decreases CTGF/CCN2‐mediated damage and fibrosis in normal and dystrophic skeletal muscles
Authors: Cabello‐Verrugio Claudio , Morales María Gabriela , Cabrera Daniel , Vio Carlos P. , Brandan Enrique
Published: June 2011

Connective tissue growth factor (CTGF/CCN‐2) is mainly involved in the induction of extracellular matrix (ECM) proteins. The levels of CTGF correlate with the degree and severity of fibrosis in many tissues, including dystrophic skeletal muscle. The CTGF overexpression in tibialis anterior skeletal muscle using an adenoviral vector reproduced many of the features observed in dystrophic muscles including muscle damage and regeneration, fibrotic response and decrease in the skeletal muscle strength. The renin–angiotensin system is involved in the genesis and progression of fibrotic diseases through its main fibrotic components angiotensin‐II and its transducer receptor AT‐1. The use of AT‐1 receptor blockers (ARB) has been shown to decrease fibrosis. In this paper, we show the effect of AT‐1 receptor blockade on CTGF‐dependent biological activity in skeletal muscle cells as well as the response to CTGF overexpression in normal skeletal muscle. Our results show that in myoblasts ARB decreased CTGF‐mediated increase of ECM protein levels, extracellular signal regulated kinases 1/2 (ERK‐1/2) phosphorylation and stress fibres formation. In tibialis anterior muscle overexpressing CTGF using an adenovirus, ARB treatment decreased CTGF‐mediated increase of ECM molecules, α‐SMA and ERK‐1/2 phosphorylation levels. Quite remarkable, ARB was able to prevent the loss of contractile force of tibialis anterior muscles overexpressing CTGF. Finally, we show that ARB decreased the levels of fibrotic proteins, CTGF and ERK‐1/2 phosphorylation augmented in a dystrophic skeletal muscle from mdx mice. We propose that ARB is a novel pharmacological tool that can be used to decrease the fibrosis induced by CTGF in skeletal muscle associated with muscular dystrophies.
Characterization of human‐type monoclonal antibodies against reduced form of hemin binding protein 35 from Porphyromonas gingivalis
Authors: Shibata Y. , Okano S. , Shiroza T. , Tahara T. , Nakazawa K. , Kataoka S. , Ishida I. , Kobayashi T. , Yoshie H. , Abiko Y.
Published: June 2011

Shibata Y, Okano S, Shiroza T, Tahara T, Nakazawa K, Kataoka S, Ishida I, Kobayashi T, Yoshie H, Abiko Y. Characterization of human‐type monoclonal antibodies against reduced form of hemin binding protein 35 from Porphyromonas gingivalis. J Periodont Res 2011; 46: 673–681. © 2011 John Wiley & Sons A/S

Background and Objective:  The gram‐negative anaerobe Porphyromonas gingivalis has been implicated as an important pathogen in the development of adult periodontitis, and its colonization of subgingival sites is critical in the pathogenic process. We previously identified a 35 kDa surface protein (hemin binding protein 35; HBP35) from P. gingivalis that exhibited coaggregation activity, while additional analysis suggested that this protein possessed an ability to bind heme molecules. For development of passive immunotherapy for periodontal diseases, human‐type monoclonal antibodies have been prepared using HBP35 as an antigen in TransChromo mice. In the present study, we focused on a single antibody, TCmAb‐h13, which is known to inhibit heme binding to recombinant HBP35. The aim of our investigation was to clarify the redox‐related function of HBP35 and consider the benefits of human‐type monoclonal antibodies.

Material and Methods:  To examine the antigen recognition capability of TCmAbs with immunoblotting and Biacore techniques, we used the native form as well as several Cys‐to‐Ser variants of recombinant HBP35.

Results:  We found that the redox state of recombinant HBP35 was dependent on two Cys residues, 48C and 51C, in the thioredoxin active center (WCGxCx). Furthermore, TCmAb‐h13 recognized the reduced forms of recombinant HBP35, indicating its inhibitory effect on P. gingivalis growth.

Conclusion:  Hemin binding protein 35 appears to be an important molecule involved in recognition of the redox state of environmental conditions. In addition, TCmAb‐h13 had an inhibitory effect on heme binding to recombinant HBP35, thereby interfering with P. gingivalis growth.
Body composition measured by dual‐energy X‐ray absorptiometry half‐body scans in obese children
Authors: Breithaupt P , Colley RC , Adamo KB
Published: June 2011

Aim:  To perform a methods comparison of a left or right half‐body scan versus whole‐body scan for measuring body composition in a sample of obese children.

Methods:  A group of obese children (n = 58; ≥95th BMI percentile; 8–18 years) were required to undergo a dual‐energy X‐ray absorptiometry (DXA) body composition measurement as part of an ongoing cohort study; 34 fit within the imaging field of the DXA scanner and were eligible for inclusion in the present analysis. Percent fat, total mass, fat mass, lean mass and bone mineral content (BMC) were estimated from half‐body scans and compared with the whole‐body results. Assessment was completed using GE enCORE 11.40 software.

Results:  In comparing left‐ and right‐side scans to whole‐body scans, there was significant correlation for all body composition variables (p ≤ 0.005, R2 = 0.996–1.0). Bland Altman analyses also showed high levels of agreement between half‐body estimates and whole‐body measurements.

Conclusion:  This study supports using a half‐body scan methodology for percent fat, total mass, fat mass, lean mass, and BMC as a valid alternative to full‐body analysis in obese children and youth.
N-Terminal Probrain Natriuretic Peptide as a Biomarker of Cardioembolic Stroke
Authors: Fonseca Ana Catarina , Matias Joaquim Sampaio , e Melo Teresa Pinho , Falcão Filipa , Canhão Patrícia , Ferro José M.
Published: June 2011

Background and purpose

N-terminal probrain natriuretic peptide, which is mainly produced by the heart, is increased in acute stroke. We aimed to determine if N-terminal probrain natriuretic peptide could be a biomarker for ischemic stroke with a cardioembolic cause.

Methods

Consecutive sample of acute stroke patients admitted to a Stroke Unit. Ischemic stroke subtype was classified using the TOAST classification. Blood samples were drawn within 72 h after stroke onset. Serum N-terminal probrain natriuretic peptide concentration was measured using an electrochemiluminescence immunoassay. Mean values of N-terminal probrain natriuretic peptide were compared between patients with hemorrhagic stroke vs. ischemic stroke, cardioembolic stroke vs. noncardioembolic stroke, cardioembolic stroke with atrial fibrillation vs. noncardioembolic stroke using t-test. Receiver operating characteristic curves were used to test the ability of N-terminal probrain natriuretic peptide values to identify cardioembolic stroke and cardioembolic stroke with atrial fibrillation.

Results

Ninety-two patients were included (66 with ischemic stroke) with a mean age of 58·6 years. Twenty-eight (42·4%) ischemic strokes had a cardioembolic cause. Mean N-terminal probrain natriuretic peptide values for cardioembolic stroke were significantly higher ( P < 0·001) (491·6; 95% confidence interval 283·7–852·0 pg/ml) than for noncardioembolic ischemic stroke (124·7; 86·3–180·2 pg/ml). The area under the receiver operating characteristic curve for N-terminal probrain natriuretic peptide in cardioembolic stroke was 0·77. The cut-off point with the highest sensitivity and specificity was set at 265·5 pg/ml (71·4% and 73·7% respectively). The area under the curve of N-terminal probrain natriuretic peptide for cardioembolic stroke related to atrial fibrillation was 0·92, cut-off was set at 265·5 pg/ml (sensitivity 94·4%, specificity 72·9%).

Conclusion

N-terminal probrain natriuretic peptide is a biomarker with a good accuracy to predict ischemic stroke of cardioembolic cause, namely associated with atrial fibrillation.
Outcomes in Acute Ischemic Strokes Presenting with Disabling Neurologic Deficits without Intracranial Vascular Occlusion
Authors: Shobha Nandavar , Bhatia Rohit , Boyko Matthew , Tymchuk Sarah , Kumarpillai Gopukumar , Smith Eric , Demchuk Andrew M.
Published: June 2011

Background

Patients with moderate to severe acute ischemic stroke without intracranial vessel occlusion are an intriguing subset of stroke patients. They pose diagnostic and therapeutic challenges to the physician. We sought to study these patients with an emphasis on their radiological and clinical outcomes.

Methods

This is a retrospective cohort study of ischemic stroke patients (NIHSS ≥ 6), with no intracranial vessel occlusion on computed tomography angiography within six-hours of symptom onset. Follow-up imaging – either computed tomography brain or magnetic resonance imaging – was performed within one- to seven-days. The primary outcome was modified Rankin Scale score ≤ 2 at three-months.

Results

In a database of 1308 patients, we identified 99 (7·6%) patients with NIHSS≥6 and no intracranial vessel occlusion on computed tomography angiography. The mean age was 67·8 ± 15·4 years and 60 (60·6%) were men. The median baseline NIHSS was nine (6–28). The initial computed tomography head was normal in 79 (79·8%) patients. Dramatic early clinical improvement at 24 h (NIHSS score ≤2 at 24 h or change between baseline and 24 h NIHSS score 15 points) was seen in 38 (38·4%) patients. Follow-up scans showed infarcts in 66 (66·7%) patients. Fifty (50·5%) patients received tissue plasminogen activator; one (2%) tissue plasminogen activator-treated patient developed symptomatic intracranial hemorrhage. At three-months; 59 (59·6%) patients were independent (modified Rankin Scale ≤2), 34 (34·3%) patients were dependent (modified Rankin Scale 3–5), and six (6·1%) were dead. The factors associated with the unlikelihood of good outcome were higher initial NIHSS (odds ratio 0·86 per additional point, 95% confidence interval 0·77–0·95, P = 0·003), and older age (odds ratio 0·95 per additional year, 95% confidence interval 0·92–0·98, P = 0·004).

Conclusion

Stroke without intracranial occlusions are not a benign entity. Factors that are independently associated with decreased likelihood of a good outcome are higher baseline NIHSS, and older age. Treatment with tissue plasminogen activator is not a predictor of outcome.
Red Cell Distribution Width Does Not Predict Stroke Severity or Functional Outcome
Authors: Ntaios George , Gurer Ozgur , Faouzi Mohamed , Aubert Carole , Michel Patrik
Published: June 2011

Introduction

Red cell distribution width was recently identified as a predictor of cardiovascular and all-cause mortality in patients with previous stroke. Red cell distribution width is also higher in patients with stroke compared with those without. However, there are no data on the association of red cell distribution width, assessed during the acute phase of ischemic stroke, with stroke severity and functional outcome. In the present study, we sought to investigate this relationship and ascertain the main determinants of red cell distribution width in this population.

Methods

We used data from the Acute Stroke Registry and Analysis of Lausanne for patients between January 2003 and December 2008. Red cell distribution width was generated at admission by the Sysmex XE-2100 automated cell counter from ethylene diamine tetraacetic acid blood samples stored at room temperature until measurement. An χ2-test was performed to compare frequencies of categorical variables between different red cell distribution width quartiles, and one-way analysis of variance for continuous variables. The effect of red cell distribution width on severity and functional outcome was investigated in univariate and multivariate robust regression analysis. Level of significance was set at 95%.

Results

There were 1504 patients (72±15·76 years, 43·9% females) included in the analysis. Red cell distribution width was significantly associated to NIHSS ( β-value=0·24, P=0·01) and functional outcome (odds ratio=10·73 for poor outcome, P<0·001) at univariate analysis but not multivariate. Prehospital Rankin score ( β=0·19, P<0·001), serum creatinine ( β=0·008, P<0·001), hemoglobin ( β=−0·009, P<0·001), mean platelet volume ( β=0·09, P<0·05), age ( β=0·02, P<0·001), low ejection fraction ( β=0·66, P<0·001) and antihypertensive treatment ( β=0·32, P<0·001) were independent determinants of red cell distribution width.

Conclusions

Red cell distribution width, assessed during the early phase of acute ischemic stroke, does not predict severity or functional outcome.
Calculation of Numbers-Needed-To-Treat in Parallel Group Trials Assessing Ordinal Outcomes: Case Examples from Acute Stroke and Stroke Prevention
Authors: Bath Philip , Hogg Cheryl , Tracy Michael , Pocock Stuart
Published: June 2011

Background

Number-needed-to-treat describes the magnitude of the effect of an intervention, underpins health economic analyses, and is typically calculated for binary events. Ordered categorical outcomes provide more clinical information and their analysis using ordinal approaches is usually more efficient statistically. However, to date, techniques to calculate number-needed-to-treat based on ordinal outcomes for parallel group trials have had important limitations.

Aims

Numbers-needed-to-treat may be calculated for ordinal data from parallel group trials by using an unmatched comparison of all subjects or by generating matched pairs of patients nested within the study.

Methods

The above approaches were assessed and compared with numbers-needed-to-treat calculated for binary outcomes using individual patient data from acute and prevention stroke trials testing the effect of interventions of varying utility and efficacy.

Results

Numbers-needed-to-treat were generally lower numerically for ordinal vs. binary, and matched vs. unmatched analyses, and the lowest in highly efficacious interventions: hemicraniectomy, ordinal matched 2·4 vs. ordinal unmatched 2·5 vs. binary matched 12 vs. binary unmatched 9 (one trial, 12 month outcome); alteplase, 4·5 vs. 6·6 vs. 8·4 vs. 8·4 (one trial with two parts, three-months); aspirin, 42 vs. 58 vs. 76 vs. 80 (one trial, six-months); and stroke units, 3·6–5·3 vs. 6·2 vs. 4·7–5·9 vs. 6·3–7·0 (two trials, three- to 60 months). Similar trends were seen for aspirin/dipyridamole vs. aspirin in secondary prevention, 22 vs. 20 vs. 31 vs. 31 (one trial, 24 months).

Conclusions

Number-needed-to-treat may be calculated for ordinal outcome data derived from parallel group stroke trials; such numbers-needed-to-treat are lower than those calculated for binary outcomes. Their use complements the use of ordinal statistical approaches in the analysis of ordered categorical data.
Aims and Results of the NIMH Systematic Treatment Enhancement Program for Bipolar Disorder (STEP‐BD)
Authors: Bowden C.L. , Perlis R.H. , Thase M.E. , Ketter T.A. , Ostacher M.M. , Calabrese J.R. , Reilly‐Harrington N.A. , Gonzalez J.M. , Singh V. , Nierenberg A.A. , Sachs G.S.
Published: June 2011

The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP‐BD) was funded as part of a National Institute of Mental Health initiative to develop effectiveness information about treatments, illness course, and assessment strategies for severe mental disorders. STEP‐BD studies were planned to be generalizable both to the research knowledge base for bipolar disorder and to clinical care of bipolar patients. Several novel methodologies were developed to aid in illness characterization, and were combined with existing scales on function, quality of life, illness burden, adherence, adverse effects, and temperament to yield a comprehensive data set. The methods integrated naturalistic treatment and randomized clinical trials, which a portion of STEP‐BD participants participated. All investigators and other researchers in this multisite program were trained in a collaborative care model with the objective of retaining a high percentage of enrollees for several years. Articles from STEP‐BD have yielded evidence on risk factors impacting outcomes, suicidality, functional status, recovery, relapse, and caretaker burden. The findings from these studies brought into question the widely practiced use of antidepressants in bipolar depression as well as substantiated the poorly responsive course of bipolar depression despite use of combination strategies. In particular, large studies on the characteristics and course of bipolar depression (the more pervasive pole of the illness), and the outcomes of treatments concluded that adjunctive psychosocial treatments but not adjunctive antidepressants yielded outcomes superior to those achieved with mood stabilizers alone. The majority of patients with bipolar depression concurrently had clinically significant manic symptoms. Anxiety, smoking, and early age of bipolar onset were each associated with increased illness burden. STEP‐BD has established procedures that are relevant to future collaborative research programs aimed at the systematic study of the complex, intrinsically important elements of bipolar disorders.
Multiple In‐Cycle Transshipments with Positive Delivery Times
Authors: Çömez Nagihan , Stecke Kathryn E. , Çakanyıldırım Metin
Published: June 2011

We study a centralized inventory sharing system of two retailers that are replenished periodically. Between two replenishments, a unit can be transshipped to a stocked‐out retailer from the other. It arrives a transshipment time later, during which the stocked‐out retailer incurs backorder cost. Without transshipment, backorder cost is incurred until the next replenishment. Since the transshipment time is shorter than the time between two replenishments, transshipments can reduce the backorder cost at the stocked‐out retailer and the holding costs at the other retailer. The system is directed by a centralized inventory manager, who minimizes the long‐run average cost consisting of replenishment, holding, backorder, and transshipment costs. The transshipment policy is characterized by hold‐back inventory levels, which are nonincreasing in the remaining time until the next replenishment. The transshipment policy differs from those in the literature because we allow for multiple transshipments between replenishments, positive transshipment times, and backorder costs. We also discuss the challenges associated with positive replenishment time and develop upper and lower bounds of average cost in this case. Bounds are numerically shown to have an average gap of 1.1%. A heuristic solution is based on the upper bound and differs from the optimal cost by at most this gap.
Understanding Voice Perception
Authors: Belin Pascal , Bestelmeyer Patricia E. G. , Latinus Marianne , Watson Rebecca
Published: June 2011

Voices carry large amounts of socially relevant information on persons, much like ‘auditory faces'. Following Bruce and Young (1986)'s seminal model of face perception, we propose that the cerebral processing of vocal information is organized in interacting but functionally dissociable pathways for processing the three main types of vocal information: speech, identity, and affect. The predictions of the ‘auditory face' model of voice perception are reviewed in the light of recent clinical, psychological, and neuroimaging evidence.
Distinct cellular properties of identified dopaminergic and GABAergic neurons in the mouse ventral tegmental area
Authors: Chieng Billy , Azriel Yael , Mohammadi Sarasa , Christie MacDonald J.
Published: June 2011

Non‐technical summary The lower mid‐brain of rodent is home to addiction and hedonism of substances of abuse. Due to overlapping physiological properties among different types of nerve cell within this brain region, it has been difficult to selectively study the physiology of a single type of nerve cell. Here, using gene technology together with selective antibody detection, we have exclusively identified the two dominant populations of nerve cells and found dopamine‐containing cells five times more abundant. We found clear non‐overlapping cellular characteristics between the two types that are unequivocal predictors for selection of nerve cells, whilst other previously employed cellular criteria were found to be less useful.
The Unravelling of Open-Ended Single Walled Carbon Nanotubes Using Molecular Dynamics Simulations
Authors: Ragab Tarek , Basaran Cemal
Published: June 2011

The unravelling of (10, 10) and (18, 0) single-walled carbon nanotubes (SWCNTs) is simulated using molecular dynamics simulations at different temperatures. Two different schemes are proposed to simulate the unravelling; completely restraining the last atom in the chain and only restraining it in the axial direction. The forces on the terminal atom in the unravelled chain in the axial and radial directions are reported till the separation of the atomic chain from the carbon nanotube structure. The force-displacement relation for a chain structure at different temperatures is calculated and is compared to the unravelling forces. The axial stresses in the body of the carbon nanotube are calculated and are compared to the failure stresses of that specific nanotube. Results show that the scheme used to unravel the nanotube and the temperature can only effect the duration needed before the separation of some or all of the atomic chain from the nanotube, but does not affect the unravelling forces. The separation of the atomic chain from the nanotube is mainly due to the impulsive excessive stresses in the chain due to the addition of a new atom and rarely due to the steady stresses in the chain. From the simulations, it is clear that the separation of the chain will eventually happen due to the closing structure occurring at the end of the nanotube that would not be possible in multiwalled nanotubes.
Using CFD to Study Combustion and Steam Flow Distribution Effects on Reheater Tubes Operation
Authors: Poursaeidi Esmaeil , Arablu Masoud
Published: June 2011

The thickness measurements showed that boilers of the Shahid Rajaee power plant have a non-uniform thickness in some regions of the final reheater tubes after 80,000 h of operation. Experimental tests on areas such as thickness, hardness, metallography, and recorded temperature showed that high temperature erosion is the most obvious reason for thinning in these tubes. Therefore, two possible reasons for the non-uniform tube thinning (problems due to combustion and steam mal-distribution in the tubes) were explored. This paper presents simulations of combustion, flow distribution in reheater tubes, and heat exchange process in Pass 1 of the boiler using FLUENT software. Combustion simulation results showed temperature distribution and mass flux of combustion products are not uniform at the chamber outlet. But these non-uniformities are not proportional to the tubes’ thickness non-uniformity; whereas, simulations showed steam is mal-distributed in the tubes so that steam maldistribution is proportional to the tubes’ thickness non-uniformities. Because steam maldistribution was due to mal-feeding and offloading of headers (U-type headers), all possible ways of feeding and offloading of headers were studied, and the results showed that the H-type configuration has the most uniform flow distribution.
Manifold Design for Micro-Channel Cooling With Uniform Flow Distribution
Authors: Solovitz Stephen A. , Mainka Jeffrey
Published: June 2011

High-power electronic systems often require temperature uniformity for optimal performance. While many advanced cooling systems, such as micro-channels, result in significant heat removal, they are also susceptible to flow mal-distribution that can impact the local temperature variation on a device. By examining the pressure drops through each flow path in a multi-channel cooling system, an analytical model is predicted for the optimal manifold shape to produce uniform velocities. This is a simple power law, whose exponent depends on the flow regime in the manifold passages. The model is validated for laminar fully developed conditions using a series of computational simulations. With the power law design, the speeds in a parallel channel design are uniformly distributed at low Reynolds numbers, with a standard deviation of less than 3% of the overall mean channel speed. At higher Reynolds numbers, some mal-distribution is observed due to developing flow conditions, but it is not as significant as with typical untapered designs.
Modeling and Simulation of Capillary Microfluidic Networks Based on Electrical Analogies
Authors: Kang Seok-Won , Banerjee Debjyoti
Published: June 2011

In this study we implemented the network simulation techniques using macromodels (lumped models) for capillary driven flows in microfluidic networks. The flow characteristics in a flow junction, such as meniscus stretching and bifurcation, were studied and their effects on filling time as well as pressure drop were explored for various network configurations. The results from the network simulator are validated numerically using computational fluid dynamics (CFD) simulations by employing the volume-of-fluids (VOF) method. The predictions by the network simulator for free-surface flows in different microfluidic networks were found to be in good agreement with the results obtained from the VOF simulations for filling time and meniscus position.
Shifting the Metabolic Program
Authors: Adler Elizabeth M.
Published: June 2011

Pyruvate kinase M2 interacts directly with hypoxia-inducible factor 1 to promote glycolytic metabolism.
Noncanonical Notch in Normoxia
Authors: VanHook Annalisa M.
Published: June 2011

HIF-α interacts with Notch to specify the fate of blood cells in the fly.
Making a Bid for Inflammation
Authors: Foley John F.
Published: June 2011

The proapoptotic protein Bid promotes innate immune responses in the intestine independently of its role in apoptosis.
Vibrations Beyond the Active Site
Authors: Yeston Jake
Published: June 2011

Vibrational spectroscopy coupled with isotopic substitution can probe protein structure.
Antiplasmodial Properties of Acyl-Lysyl Oligomers in Culture and Animal Models of Malaria
Authors: Zaknoon Fadia , Wein Sharon , Krugliak Miriam , Meir Ohad , Rotem Shahar , Ginsburg Hagai , Vial Henri , Mor Amram
Published: June 2011

Our previous analysis of antiplasmodial properties exhibited by dodecanoyl-based oligo-acyl-lysyls (OAKs) has outlined basic attributes implicated in potent inhibition of parasite growth and underlined the critical role of excess hydrophobicity in hemotoxicity. To dissociate hemolysis from antiplasmodial effect, we screened >50 OAKs for
in vitro
growth inhibition of
Plasmodium falciparum
strains, thus revealing the minimal requirements for antiplasmodial potency in terms of sequence and composition, as confirmed by efficacy studies
in vivo
. The most active sequence, dodecanoyllysyl-bis(aminooctanoyllysyl)-amide (C
12
K-2α
8
), inhibited parasite growth at submicromolar concentrations (50% inhibitory concentration [IC
50
], 0.3 ± 0.1 μM) and was devoid of hemolytic activity (<0.4% hemolysis at 150 μM). Unlike the case of dodecanoyl-based analogs, which equally affect ring and trophozoite stages of the parasite developmental cycle, the ability of various octanoyl-based OAKs to distinctively affect these stages (rings were 4- to 5-fold more sensitive) suggests a distinct antiplasmodial mechanism, nonmembranolytic to host red blood cells (RBCs). Upon intraperitoneal administration to mice, C
12
K-2α
8
demonstrated sustainable high concentrations in blood (e.g., 0.1 mM at 25 mg/kg of body weight). In
Plasmodium vinckei
-infected mice, C
12
K-2α
8
significantly affected parasite growth (50% effective dose [ED
50
], 22 mg/kg) but also caused mortality in 2/3 mice at high doses (50 mg/kg/day × 4).
The Expression Levels of Outer Membrane Proteins STM1530 and OmpD, Which Are Influenced by the CpxAR and BaeSR Two-Component Systems, Play Important Roles in the Ceftriaxone Resistance of
Salmonella enterica
Serovar Typhimurium
Authors: Hu Wensi S. , Chen Hung-Wen , Zhang Rui-Yang , Huang Chung-Yi , Shen Chi-Fan
Published: June 2011

Significant increases in STM3031, STM1530, and AcrD protein levels and significant decreases in OmpC and OmpD protein levels are present when the ceftriaxone-resistant
Salmonella enterica
serovar Typhimurium R200 strain is compared with the ceftriaxone-susceptible strain 01-4. AcrD is known to be involved in drug export, and STM3031 seems to play a key role in ceftriaxone resistance. Here, we examine the roles of STM1530, OmpC, and OmpD in ceftriaxone resistance. An
ompD
gene deletion mutant showed 4-fold higher ceftriaxone resistance than 01-4. An
ompC
gene deletion mutant showed 4-fold higher cephalothin and erythromycin resistance than 01-4, but there was no effect on ceftriaxone resistance. However, a
stm1530
deletion mutant did show >64-fold lower ceftriaxone resistance than R200. Moreover, the STM3031 protein was significantly decreased in R200(Δ
stm1530
) compared to R200. STM3031 expression has been shown to be influenced by the two-component system regulator gene
baeR
. CpxR seems to modulate BaeR. A
cpxA-cpxR
gene deletion mutant showed >2,048-fold lower ceftriaxone resistance than R200. The outer membrane protein profile of R200(Δ
cpxAR
) showed significant decreases in STM3031 and STM1530 compared to R200, while OmpD had returned to the level found in 01-4. Furthermore, the
stm3031
,
stm1530
, and
ompD
mRNA levels were correlated with their protein expression levels in these strains, while decreases in the mRNA levels of the efflux pump
acrB
,
acrD
, and
acrF
genes were found in R200(Δ
cpxAR
). Findings similar to those for R200(Δ
cpxAR
) were found for R200(Δ
baeSR
). These results, together with those for STM3031 and the fact that STM1530 is an outer membrane protein, suggest that STM1530 and OmpD are influenced by the CpxAR and BaeSR two-component systems and that this contributes to
S. enterica
serovar Typhimurium ceftriaxone resistance.
Emergence of NDM-1 Metallo-β-Lactamase in
Pseudomonas aeruginosa
Clinical Isolates from Serbia
Authors: Jovcic Branko , Lepsanovic Zorica , Suljagic Vesna , Rackov Gorjana , Begovic Jelena , Topisirovic Ljubisa , Kojic Milan
Published: June 2011

This work reports, for the first time, the presence of New Delhi metallo-β-lactamase 1 (NDM-1) in
Pseudomonas aeruginosa
. Moreover, this is the first report of the NDM-1 presence in the Balkan region. Cosmid gene libraries of carbapenem-nonsusceptible
Pseudomonas aeruginosa
clinical isolates MMA83 and MMA533 were screened for the presence of metallo-β-lactamases. Accordingly, both MMA83 and MMA533 carried the
bla
NDM-1
gene. Pulsed-field gel electrophoresis (PFGE) analysis indicated that strains MMA83 and MMA533 belonged to different clonal groups. Five additional isolates from different patients clonally related to either MMA83 or MMA533 were found to be NDM-1 positive.
Effect of Ciprofloxacin Concentration on the Frequency and Nature of Resistant Mutants Selected from
Pseudomonas aeruginosa mutS
and
mutT
Hypermutators
Authors: Morero Natalia R. , Monti Mariela R. , Argaraña Carlos E.
Published: June 2011

The rapid emergence of drug resistance upon treatment of
Pseudomonas aeruginosa
infections with fluoroquinolones is a serious concern. In this study, we report the effect of hypermutability on the mutant selection window for ciprofloxacin (CIP) by comparing the hypermutator MPAO1
mutS
and
mutT
strains with the wild-type strain. The mutant selection window was shifted to higher CIP concentrations for both hypermutators, presenting the
mutS
strain with a broader selection window in comparison to the wild-type strain. The mutation prevention concentrations (MPC) determined for
mutT
and
mutS
strains were increased 2- and 4-fold over the wild-type level, respectively. In addition, we analyzed the molecular bases for resistance in the bacterial subpopulations selected at different points in the window. At the top of the window, the resistant clones isolated were mainly mutated in GyrA and ParC topoisomerase subunits, while at the bottom of the window, resistance was associated with the overexpression of MexCD-OprJ and MexAB-OprM efflux pumps. Accordingly, a greater proportion of multidrug-resistant clones were found among the subpopulations isolated at the lower CIP concentrations. Furthermore, we found that the exposure to CIP subinhibitory concentrations favors the accumulation of cells overexpressing MexCD-OprJ (due to mutations in the transcriptional repressor NfxB) and MexAB-OprM efflux pumps. We discuss these results in the context of the possible participation of this antibiotic in a mutagenic process.
Passive Immunization with a Polyclonal Antiserum to the Hemoglobin Receptor of Haemophilus ducreyi Confers Protection against a Homologous Challenge in the Experimental Swine Model of Chancroid
Authors: Leduc Isabelle , Fusco William G. , Choudhary Neelima , Routh Patty A. , Cholon Deborah M. , Hobbs Marcia M. , Almond Glen W. , Orndorff Paul E. , Elkins Christopher
Published: June 2011

Haemophilus ducreyi
, the etiologic agent of chancroid, has an obligate requirement for heme. Heme is acquired by
H. ducreyi
from its human host via TonB-dependent transporters expressed at its bacterial surface. Of 3 TonB-dependent transporters encoded in the genome of
H. ducreyi
, only the hemoglobin receptor, HgbA, is required to establish infection during the early stages of the experimental human model of chancroid. Active immunization with a native preparation of HgbA (nHgbA) confers complete protection in the experimental swine model of chancroid, using either Freund's or monophosphoryl lipid A as adjuvants. To determine if transfer of anti-nHgbA serum is sufficient to confer protection, a passive immunization experiment using pooled nHgbA antiserum was conducted in the experimental swine model of chancroid. Pigs receiving this pooled nHgbA antiserum were protected from a homologous, but not a heterologous, challenge. Passively transferred polyclonal antibodies elicited to nHgbA bound the surface of
H. ducreyi
and partially blocked hemoglobin binding by nHgbA, but were not bactericidal. Taken together, these data suggest that the humoral immune response to the HgbA vaccine is protective against an
H. ducreyi
infection, possibly by preventing acquisition of the essential nutrient heme.
Serine Proteases Degrade Airway Mucins in Cystic Fibrosis
Authors: Henke Markus O. , John Gerrit , Rheineck Christina , Chillappagari Shashi , Naehrlich Lutz , Rubin Bruce K.
Published: June 2011

Airway mucins are the major molecular constituents of mucus. Mucus forms the first barrier to invading organisms in the airways and is an important defense mechanism of the lung. We confirm that mucin concentrations are significantly decreased in airway secretions of subjects with cystic fibrosis (CF) who have chronic
Pseudomonas aeruginosa
infection. In sputum from CF subjects without a history of
P. aeruginosa
, we found no significant difference in the mucin concentration compared to mucus from normal controls. We demonstrate that mucins can be degraded by synthetic human neutrophil elastase (HNE) and
P. aeruginosa
elastase B (pseudolysin) and that degradation was inhibited by serine proteases inhibitors (diisopropyl fluorophosphates [DFP], phenylmethylsulfonyl fluoride [PMSF], and 1-chloro-3-tosylamido-7-amino-2-heptanone HCl [TLCK]). The mucin concentration in airway secretions from CF subjects is similar to that for normal subjects until there is infection by
P. aeruginosa
, and after that, the mucin concentration decreases dramatically. This is most likely due to degradation by serine proteases. The loss of this mucin barrier may contribute to chronic airway infection in the CF airway.
Activation of Adenosine A2AReceptors Inhibits Neutrophil Transuroepithelial Migration
Authors: Säve Susanne , Mohlin Camilla , Vumma Ravi , Persson Katarina
Published: June 2011

Adenosine has been identified as a significant inhibitor of inflammation by acting on adenosine A2Areceptors. In this study, we examined the role of adenosine and A2Areceptors in the transmigration of human neutrophils across anin vitromodel of the transitional bladder urothelium. Human uroepithelial cells (UROtsa) were grown on transwell inserts; uropathogenicEscherichia coli(UPEC) and neutrophils were added to the transwell system; and the number of migrating neutrophils was evaluated. Reverse transcription-PCR (RT-PCR), immunohistochemistry, and flow cytometry were used to investigate the expression of adenosine receptors, the epithelial adhesion molecule ICAM-1, and the neutrophil integrin CD11b. Levels of proinflammatory interleukin-8 (IL-8) and phosphorylated IκBα were measured by enzyme-linked immunosorbent assays (ELISA) and Luminex assays, respectively. The neutrophils expressed all four adenosine receptor subtypes (A1, A2A, A2B, and A3receptors), but A3receptors were not expressed by UROtsa cells. UPEC stimulated neutrophil transuroepithelial migration, which was significantly decreased in response to the specific A2Areceptor agonist CGS 21680. The inhibitory effect of CGS 21680 on neutrophil migration was reversed by the A2Areceptor antagonist SCH 58261. The production of chemotactic IL-8 and the expression of the adhesion molecule ICAM-1 or CD11b were not significantly affected by CGS 21680. However, a significant decrease in the level of phosporylated IκBα was revealed in response to CGS 21680. In conclusion, UPEC infectionin vitroevoked neutrophil migration through a multilayered human uroepithelium. The UPEC-evoked neutrophil transmigration decreased in response to A2Areceptor activation, possibly through inhibition of NF-κB signaling pathways.
Activation of the Contact System at the Surface of Fusobacterium necrophorum Represents a Possible Virulence Mechanism in Lemièrre's Syndrome
Authors: Holm Karin , Frick Inga-Maria , Björck Lars , Rasmussen Magnus
Published: June 2011

Fusobacterium necrophorum
causes Lemièrre's syndrome, a serious disease with septic thrombophlebitis of the internal jugular vein, pulmonary involvement, and systemic inflammation. The contact system is a link between inflammation and coagulation, and contact activation by the bacteria could therefore contribute to the abnormal coagulation and inflammation seen in patients with Lemièrre's syndrome. In this study,
F. necrophorum
was found to bind radiolabeled high-molecular-weight kininogen (HK), a central component of the contact system. Binding was inhibited by the addition of unlabeled HK and domain D5 of HK but not other components of the contact system, indicating a specific interaction mediated through the D5 region. Binding of HK was significantly reduced after pretreatment of the bacteria with trypsin, suggesting that surface proteins are involved in HK binding. Incubation of the bacteria with human plasma resulted in an HK breakdown pattern suggestive of bradykinin release, and bradykinin was also detected in the supernatant. In addition, we show that factor XI (FXI), another component of the contact system, binds to
F. necrophorum
and that the bound FXI reconstitutes the activated partial thromboplastin time of FXI-deficient plasma. Thrombin activity was detected at the surface of the bacteria following incubation with plasma, indicating that the intrinsic pathway of coagulation is activated at the surface. This activity was completely blocked by inhibitors of the contact system. The combined results show that the contact system is activated at the surface of
F. necrophorum
, suggesting a pathogenic role for this system in Lemièrre's syndrome.
Assessing the concordance of health and child protection data for ‘maltreated’ and ‘unintentionally injured’ children
Authors: McKenzie Kirsten , Scott Debbie , Fraser Jennifer A , Dunne Michael P
Published: June 2011

Objectives

To quantify the concordance of hospital child maltreatment data with child protection service (CPS) records, and identify factors associated with linkage.

Methods

Multivariable logistic regression analysis was conducted following retrospective medical record review and database linkage of 884 child records from 20 hospitals and the CPS in Queensland, Australia.

Results

Nearly all children with hospital assigned maltreatment codes (93.1%) had a CPS record. Of these, 85.1% had a recent notification. 29% of the linked maltreatment group (n=113) were not known to the CPS prior to the hospital presentation. Almost one third of children with unintentional injury hospital codes were known to the CPS. Just over 24% of the linked unintentional injury group (n=34) were not known to the CPS prior to the hospital presentation but became known during or after discharge from hospital. These estimates are higher than the 2006/2007 annual rate of 2.39% of children being notified to the CPS. Rural children were more likely to link to the CPS, and children were over three times more likely to link if the index injury documentation included additional diagnoses or factors affecting their health.

Conclusions

The system for referring maltreatment cases to the CPS is generally efficient, although up to 1 in 15 children had codes for maltreatment but could not be linked to CPS data. The high proportion of children with unintentional injury codes who linked to CPS suggests that clinicians and hospital-based child protection staff should be supported by further education and training to ensure children at risk are being detected by the child protection system.
NONLINEAR TORQUE AND AIR-TO-FUEL RATIO CONTROL OF SPARK IGNITION ENGINES USING NEURO-SLIDING MODE TECHNIQUES
Authors: HUANG TING , JAVAHERIAN HOSSEIN , LIU DERONG
Published: June 2011

This paper presents a new approach for the calibration and control of spark ignition engines using a combination of neural networks and sliding mode control technique. Two parallel neural networks are utilized to realize a neuro-sliding mode control (NSLMC) for self-learning control of automotive engines. The equivalent control and the corrective control terms are the outputs of the neural networks. Instead of using error backpropagation algorithm, the network weights of equivalent control are updated using the Levenberg-Marquardt algorithm. Moreover, a new approach is utilized to update the gain of corrective control. Both modifications of the NSLMC are aimed at improving the transient performance and speed of convergence. Using the data from a test vehicle with a V8 engine, we built neural network models for the engine torque (TRQ) and the air-to-fuel ratio (AFR) dynamics and developed NSLMC controllers to achieve tracking control. The goal of TRQ control and AFR control is to track the commanded values under various operating conditions. From simulation studies, the feasibility and efficiency of the approach are illustrated. For both control problems, excellent tracking performance has been achieved.