bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epithelial Microvilli Establish an Electrostatic Barrier to Microbial Adhesion
Authors: Bennett Kaila M. , Walker Sharon L. , Lo David D. 
Published: April 2014

ABSTRACT

Microvilli are membrane extensions on the apical surface of polarized epithelia, such as intestinal enterocytes and tubule and duct epithelia. One notable exception in mucosal epithelia is M cells, which are specialized for capturing luminal microbial particles; M cells display a unique apical membrane lacking microvilli. Based on studies of M cell uptake under different ionic conditions, we hypothesized that microvilli may augment the mucosal barrier by providing an increased surface charge density from the increased membrane surface and associated glycoproteins. Thus, electrostatic charges may repel microbes from epithelial cells bearing microvilli, while M cells are more susceptible to microbial adhesion. To test the role of microvilli in bacterial adhesion and uptake, we developed polarized intestinal epithelial cells with reduced microvilli (“microvillus-minus,” or MVM) but retaining normal tight junctions. When tested for interactions with microbial particles in suspension, MVM cells showed greatly enhanced adhesion and uptake of particles compared to microvillus-positive cells. This preference showed a linear relationship to bacterial surface charge, suggesting that microvilli resist binding of microbes by using electrostatic repulsion. Moreover, this predicts that pathogen modification of electrostatic forces may contribute directly to virulence. Accordingly, the effacement effector protein Tir from enterohemorrhagic
Escherichia coli
O157:H7 expressed in epithelial cells induced a loss of microvilli with consequent enhanced microbial binding. These results provide a new context for microvillus function in the host-pathogen relationship, based on electrostatic interactions.
Characterization of Immunological Cross-Reactivity between Enterotoxigenic Escherichia coli Heat-Stable Toxin and Human Guanylin and Uroguanylin
Authors: Taxt Arne M. , Diaz Yuleima , Bacle Amélie , Grauffel Cédric , Reuter Nathalie , Aasland Rein , Sommerfelt Halvor , Puntervoll Pål 
Published: April 2014

ABSTRACT

Enterotoxigenic
Escherichia coli
(ETEC) expressing the heat-stable toxin (ST) (human-type [STh] and porcine-type [STp] variants) is among the five most important enteric pathogens in young children living in low- and middle-income countries. ST mediates diarrheal disease through activation of the guanylate cyclase C (GC-C) receptor and is an attractive vaccine target with the potential to confer protection against a wide range of ETEC strains. However, immunological cross-reactivity to the endogenous GC-C ligands guanylin and uroguanylin is a major concern because of the similarities to ST in amino acid sequence, structure, and function. We have investigated the presence of similar epitopes on STh, STp, guanylin, and uroguanylin by analyzing these peptides in eight distinct competitive enzyme-linked immunosorbent assays (ELISAs). A fraction (27%) of a polyclonal anti-STh antibody and an anti-STh monoclonal antibody (MAb) cross-reacted with uroguanylin, the latter with a 73-fold-lower affinity. In contrast, none of the antibodies raised against STp, one polyclonal antibody and three MAbs, cross-reacted with the endogenous peptides. Antibodies raised against guanylin and uroguanylin showed partial cross-reactivity with the ST peptides. Our results demonstrate, for the first time, that immunological cross-reactions between ST and the endogenous peptides can occur. However, the partial nature and low affinity of the observed cross-reactions suggest that the risk of adverse effects from a future ST vaccine may be low. Furthermore, our results suggest that this risk may be reduced or eliminated by basing an ST immunogen on STp or a selectively mutated variant of STh.
Origins of a 350-Kilobase Genomic Duplication in Mycobacterium tuberculosis and Its Impact on Virulence
Authors: Domenech Pilar , Rog Anya , Moolji Jalal-ud-din , Radomski Nicolas , Fallow Ashley , Leon-Solis Lizbel , Bowes Julia , Behr Marcel A. , Reed Michael B. 
Published: April 2014

ABSTRACTIn the present study, we have investigated the evolution and impact on virulence of a 350-kb genomic duplication present in the most recently evolved members of theMycobacterium tuberculosisEast Asian lineage. In a mouse model of infection, comparing HN878 subclones HN878-27 (no duplication) and HN878-45 (with the 350-kb duplication) revealed that the latter is impaired forin vivogrowth during the initial 3 weeks of infection. Furthermore, the median survival time of mice infected with isolate HN878-45 is significantly longer (77 days) than that of mice infected with HN878-27. Whole-genome sequencing of both isolates failed to reveal any mutational events other than the duplication that could account for such a substantial difference in virulence. Although we and others had previously speculated that the 350-kb duplication arose in response to some form of host-applied selective pressure (P. Domenech, G. S. Kolly, L. Leon-Solis, A. Fallow, M. B. Reed, J. Bacteriol.192:4562–4570, 2010, and B. Weiner, J. Gomez, T. C. Victor, R. M. Warren, A. Sloutsky, B. B. Plikaytis, J. E. Posey, P. D. van Helden, N. C. Gey van Pittius, M. Koehrsen, P. Sisk, C. Stolte, J. White, S. Gagneux, B. Birren, D. Hung, M. Murray, J. Galagan, PLoS One7:e26038, 2012), here we show that this large chromosomal amplification event is very rapidly selected within standardin vitrobroth cultures in a range of isolates. Indeed, subclones harboring the duplication were detectable after just five rounds ofin vitropassage. In contrast, the duplication appears to be highly unstablein vivoand is negatively selected during the later stages of infection in mice. We believe that the rapidin vitroevolution ofM. tuberculosisis an underappreciated aspect of its biology that is often ignored, despite the fact that it has the potential to confound the data and conclusions arising from comparative studies of isolates at both the genotypic and phenotypic levels.
A retrospective cohort study identifying the principal pathological features useful in the diagnosis of inclusion body myositis
Authors: Brady Stefen , Squier Waney , Sewry Caroline , Hanna Michael , Hilton-Jones David , Holton Janice L 
Published: April 2014

ObjectiveThe current pathological diagnostic criteria for sporadic inclusion body myositis (IBM) lack sensitivity. Using immunohistochemical techniques abnormal protein aggregates have been identified in IBM, including some associated with neurodegenerative disorders. Our objective was to investigate the diagnostic utility of a number of markers of protein aggregates together with mitochondrial and inflammatory changes in IBM.DesignRetrospective cohort study. The sensitivity of pathological features was evaluated in cases of Griggs definite IBM. The diagnostic potential of the most reliable features was then assessed in clinically typical IBM with rimmed vacuoles (n=15), clinically typical IBM without rimmed vacuoles (n=9) and IBM mimics—protein accumulation myopathies containing rimmed vacuoles (n=7) and steroid-responsive inflammatory myopathies (n=11).SettingSpecialist muscle services at the John Radcliffe Hospital, Oxford and the National Hospital for Neurology and Neurosurgery, London.ResultsIndividual pathological features, in isolation, lacked sensitivity and specificity. However, the morphology and distribution of p62 aggregates in IBM were characteristic and in a myopathy with rimmed vacuoles, the combination of characteristic p62 aggregates and increased sarcolemmal and internal major histocompatibility complex class I expression or endomysial T cells were diagnostic for IBM with a sensitivity of 93% and specificity of 100%. In an inflammatory myopathy lacking rimmed vacuoles, the presence of mitochondrial changes was 100% sensitive and 73% specific for IBM; characteristic p62 aggregates were specific (91%), but lacked sensitivity (44%).ConclusionsWe propose an easily applied diagnostic algorithm for the pathological diagnosis of IBM. Additionally our findings support the hypothesis that many of the pathological features considered typical of IBM develop later in the disease, explaining their poor sensitivity at disease presentation and emphasising the need for revised pathological criteria to supplement the clinical criteria in the diagnosis of IBM.
Development of evidence-based Australian medication-related indicators of potentially preventable hospitalisations: a modified RAND appropriateness method
Authors: Caughey Gillian E , Kalisch Ellett Lisa M , Wong Te Ying 
Published: April 2014

ObjectiveIndicators of potentially preventable hospitalisations have been adopted internationally as a measure of health system performance; however, few assess appropriate processes of care around medication use, that if followed may prevent hospitalisation. The aim of this study was to develop and validate evidence-based medication-related indicators of potentially preventable hospitalisations.SettingAustralian primary healthcare.ParticipantsMedical specialists, general practitioners and pharmacists. A modified RAND appropriateness method was used for the development of medication-related indicators of potentially preventable hospitalisations, which included a literature review, assessment of the strength of the supporting evidence base, an initial face and content validity by an expert panel, followed by an independent assessment of indicators by an expert clinical panel across various disciplines, using an online survey.Primary outcome measureAnalysis of ratings was performed on the four key elements of preventability; the medication-related problem must be recognisable, the adverse outcomes foreseeable and the causes and outcomes identifiable and controllable.ResultsA total of 48 potential indicators across all major disease groupings were developed based on level III evidence or greater, that were independently assessed by 78 expert clinicians (22.1% response rate). The expert panel considered 29 of these (60.4%) sufficiently valid. Of these, 21 (72.4%) were based on level I evidence.ConclusionsThis study provides a set of face and content validated indicators of medication-related potentially preventable hospitalisations, linking suboptimal processes of care and medication use with subsequent hospitalisation. Further analysis is required to establish operational validity in a population-based sample, using an administrative health database. Implementation of these indicators within routine monitoring of healthcare systems will highlight those conditions where hospitalisations could potentially be avoided through improved medication management.
Evaluation of screening criteria for palliative care consultation in the MICU: a multihospital analysis
Authors: Zalenski Robert , Courage Cheryl , Edelen Alexandra , Waselewsky Denise , Krayem Hicham , Latozas Jordana , Kaufman David 
Published: April 2014

BackgroundThere are currently no comprehensive studies in critical care settings that have set out to examine the association of palliative care screening criteria with multiple, adverse patient outcomes.MethodsA 7-item palliative care screen was developed from consensus reports. Medical intensive care unit (MICU) nurses at four hospitals screened patients upon admission during a 16-week period. Outcomes included percentage of patients screened and their percentage with consultations ordered. Patient screen scores were compared with mortality, hospice discharge and length of stay (LOS).ResultsDuring the period, 1071 patients were admitted to MICUs, of which, 59.3% were screened; 35.3% of patients screened positive. Patients with positive screens (n=225) were more likely to have a consult ordered (33.6% vs 3.4%; p<0.001), and likelihood of consult increased with higher screen scores. Patients with positive screens had significantly longer hospital and MICU LOS (p<0.001), and had increased risk of inpatient mortality (p<0.001) and hospice discharge (p<0.001). Criteria of ‘admission from a skilled nursing facility’ and ‘readmission to the ICU’ were significant predictors of LOS; ‘cancer,’ ‘post cardiac arrest,’ and ‘team perceived need’ were predictors of the composite variable of mortality/hospice discharge. ‘End-stage dementia’ and ‘intracranial bleed’ were not predictive of adverse outcomes.ConclusionsDecisions on the appropriateness for palliative care consultation in the MICU can be aided using a trigger screen. We recommend the use of this screen be considered in the MICU with the suggested revisions. Additional studies are needed to determine if the use of the trigger screen is associated with improved clinical outcomes.
Mycotic aneurysm detection rates with cerebral angiography in patients with infective endocarditis
Authors: Hui Ferdinand K , Bain Mark , Obuchowski Nancy A , Gordon Steven , Spiotta Alejandro M , Moskowitz Shaye , Toth Gabor , Hussain Shazam 
Published: April 2014

BackgroundCerebral angiography remains the gold standard for the detection of mycotic aneurysms, and it has been estimated that ruptured mycotic aneurysms result in 5% of the neurological complications of patients with infective endocarditis (IE).ObjectiveTo determine the diagnostic yield of cerebral angiography in the above patient population and to assess patient factors that might suggest greater or lesser utility.MethodsWe retrospectively reviewed 168 patients who underwent cerebral angiography with a diagnosis of IE or infected left ventricular assist device at the Cleveland Clinic between January 2003 and March 2010 in accordance with institutional review board guidelines. Chart and imaging review was performed.Results15/168 patients (8.9%) had mycotic aneurysms; 93.3% (14/15) of the patients with mycotic aneurysms presented with CNS hemorrhage and 66.7% (10/15) had acute ischemic findings. Of the 15 patients with mycotic aneurysms on angiography, seven underwent CT angiography and six underwent MR angiography, which showed mycotic aneurysms in three (42.9%) and two cases (one of which was questionable; 33.3%), respectively.ConclusionsPatients with IE or similar sources of central bacterial emboli are prone to neurovascular complications. Approximately 9% of patients with IE at our institution who undergo cerebral angiography have mycotic aneurysms. Presentation with hemorrhage appears to be more predictive of aneurysm, as approximately 22% of patients with IE and hemorrhage were found to have an aneurysm compared with only 1% when hemorrhage was absent. Thus, patients with IE presenting with intracranial hemorrhage should undergo vascular imaging, preferably with cerebral angiography.
Balloon remodeling of complex anterior communicating artery aneurysms: technical considerations and complications
Authors: Moon Karam , Albuquerque Felipe C , Ducruet Andrew F , Crowley R Webster , McDougall Cameron G 
Published: April 2014

IntroductionReports of the limitations and feasibility of balloon remodeling for treatment of complex anterior communicating artery (ACoA) aneurysms are scarce.MethodsNinety-nine patients were treated with balloon-assisted coil embolization for ACoA aneurysms between August 2004 and October 2012. Records were reviewed for aneurysm characteristics, balloon trajectory (vessel and side), bilateral access, treatment-related complications, and aneurysm recurrence determined by magnetic resonance angiography (MRA). Morphological outcomes following treatment were categorized into Raymond class I, II, or III.ResultsFifty-three aneurysms (53.5%) were unruptured and 46 (46.4%) were ruptured. Aneurysmal occlusion (Raymond I or II) was achieved in 89 patients (89.9%); three (3.0%) were incompletely embolized and treatment was aborted in six (6.1%). Balloon trajectories were from the A1 to either the ipsilateral or contralateral A2. In 17 cases (17.2%), bilateral A1 access was used to achieve balloon protection of the contralateral A2. In four cases (4.0%), balloon remodeling was aborted due to technical difficulty. There were 15 (15.2%) treatment-related complications; five (5.1%) were intraoperative ruptures, one of which resulted in a neurological deficit and another in death. All other complications were clinically silent, producing a permanent complication rate of 2.0%. Mean radiographic follow-up was 2.5 years, and six patients (6.1%) were retreated for recurrence or known remnant.ConclusionsBalloon remodeling should be considered for broad-based complex ACoA aneurysms. This technique provides a high rate of aneurysm occlusion with an acceptable complication profile, and avoids the need for dual antiplatelet therapy. The balloon trajectory will depend on aneurysm morphology and bilateral access may be useful in selected cases.
A SIMPLE ARRAY VERSION OF M-HEAP
Authors: JUNG HAEJAE 
Published: April 2014

Both the post-order heap and the M-heap have a full binary tree structure and have constant amortized insertion and O(logn) deletion time complexities. This paper proposes a simple array version of the M-heap, called AM-heap. The AM-heap has a complete binary tree structure and its array indexing scheme is the same as the simple indexing scheme of the conventional binary heap. An insertion on an AM-heap takes constant amortized time and a deletion takes O(logn) time where n is the number of elements in an AM-heap. The AM-heap resolves the open problem that is to design an array version of the M-heap. Also, it is simpler than the post-order heap to implement and debug.
APPROXIMATING ASYMMETRIC TSP IN EXPONENTIAL TIME
Authors: GOLOVNEV ALEXANDER 
Published: April 2014

Let G be a complete directed graph with n vertices and integer edge weights in range [0,M]. It is well known that an optimal Traveling Salesman Problem (TSP) in G can be solved in 2n time and space (all bounds are given within a polynomial factor of the input length, i.e., poly(n, log M)) and this is still the fastest known algorithm. If we allow a polynomial space only, then the best known algorithm has running time 4nnlog n. For TSP with bounded weights there is an algorithm with 1.657n · M running time. It is a big challenge to develop an algorithm with 2n time and polynomial space. Also, it is well-known that TSP cannot be approximated within any polynomial time computable function unless P=NP. In this short note we propose a very simple algorithm that, for any 0 < ε < 1, finds (1+ε)-approximation to asymmetric TSP in 2nε−1 time and ε−1 · poly(n, log M) space. Thereby, for any fixed ε, the algorithm needs 2n steps and polynomial space to compute (1 + ε)-approximation.
THE RANGES OF STATE COMPLEXITIES FOR COMPLEMENT, STAR, AND REVERSAL OF REGULAR LANGUAGES
Authors: JIRÁSKOVÁ GALINA 
Published: April 2014

We examine the deterministic and nondeterministic state complexity of complements, stars, and reversals of regular languages. Our results are as follows: (1) The nondeterministic state complexity of the complement of an n-state nfa language over a five-letter alphabet may reach each value from log n to 2n. (2) The state complexity of the star (reversal) of an n-state dfa language over a growing alphabet may reach each value from 1 to [Formula: see text] (from log n to 2n, respectively). (3) The nondeterministic state complexity of the star (reversal) of an n-state nfa binary language may reach each value from 1 to n + 1 (from n - 1 to n + 1, respectively). We also obtain some partial results on the nondeterministic state complexity of complements of binary regular languages. As a bonus, we get an exponential number of values that are non-magic in the binary case.
Hardware Acceleration for an Accurate Stereo Vision System Using Mini-Census Adaptive Support Region
Authors: Shan Yi , Hao Yuchen , Wang Wenqiang , Wang Yu , Chen Xu , Yang Huazhong , Luk Wayne 
Published: April 2014

Domain of stereo vision is highly important in the fields of autonomous cars, video tolling, robotics, and aerial surveys. The specific feature of this domain is that we should handle not only the pixel-by-pixel 2D processing in one image but also the 3D processing for depth estimation by comparing information about a scene from several images with different perspectives. This feature brings challenges to memory resource utilization, because an extra dimension of data has to be buffered. Due to the memory limitation, few of previous stereo vision implementations provide both accurate and high-speed processing for high-resolution images at the same time.
To achieve domain-specific acceleration for stereo vision, the memory limitation has to be addressed. This article uses a Mini-Census ADaptive Support Region (MCADSR) stereo matching algorithm as a case study due to its high accuracy and representative operations in this domain. To relieve the memory limitation and achieve high-speed processing, the article proposes several efficient optimization methods including vertical-first cost aggregation, hybrid parallel processing, and hardware-friendly integral image. The article also presents a customizable system which provides both accurate and high-speed stereo matching for high-resolution images. The benefits of applying the optimization methods to the system are highlighted.
With the aforesaid optimization and specific customization implemented on FPGA, the demonstrated system can process 47.6 fps (frames per second) and 129 fps for video size of 1920 × 1080 with a large disparity range of 256 and 1024 × 768 with a disparity range of 128, respectively. Our results are up to 1.64 times better than previous work in terms of Million Disparity Estimation per second (MDE/s). For accuracy, the 7.65% overall average error rate outperforms current work which can provide real-time processing with this high-resolution and large disparity range.
Chemotherapeutic Targeting of Cancer-Induced Immunosuppressive Cells
Authors: Alizadeh Darya , Larmonier Nicolas 
Published: April 2014

Abstract
The expansion of immunosuppressive cells represents a cardinal strategy deployed by tumors to escape from detection and elimination by the immune system. Regulatory T lymphocytes (Treg) and myeloid-derived suppressor cells (MDSC), major components of these inhibitory cellular networks, have drawn intense scrutiny in recent years. In patients with cancer and in animal tumor models, these suppressor cells accumulate in the tumor microenvironment, secondary lymphoid tissues, and in the blood. Equipped with the ability to suppress innate and adaptive anticancer immunity, these cells also foster disease development by promoting tumor neoangiogenesis and by enhancing cancer metastasis. They therefore represent major impediments for anticancer therapies, particularly for immune-based interventions. Recent work has provided evidence that beyond their direct cytotoxic or cytostatic effects on cancer cells, several conventional chemotherapeutic drugs and agents used in targeted therapies can promote the elimination or inactivation of suppressive Tregs or MDSCs, resulting in enhanced antitumor immunity. We analyze findings pertinent to this concept, discuss the possible molecular bases underlying the selective targeting of these immunosuppressive cells by antineoplastic agents, and consider current challenges and future prospects related to the integration of these molecules into more efficient anticancer chemoimmunotherapeutic strategies. Cancer Res; 74(10); 2663–8. ©2014 AACR.