bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vibrio cholerae-Induced Inflammation in the Neonatal Mouse Cholera Model
Authors: Bishop Anne L. , Patimalla Bharathi , Camilli Andrew 
Published: April 2014

ABSTRACT

Vibrio cholerae
is the causative agent of the acute diarrheal disease of cholera. Innate immune responses to
V. cholerae
are not a major cause of cholera pathology, which is characterized by severe, watery diarrhea induced by the action of cholera toxin. Innate responses may, however, contribute to resolution of infection and must be required to initiate adaptive responses after natural infection and oral vaccination. Here we investigated whether a well-established infant mouse model of cholera can be used to observe an innate immune response. We also used a vaccination model in which immunized dams protect their pups from infection through breast milk antibodies to investigate innate immune responses after
V. cholerae
infection for pups suckled by an immune dam. At the peak of infection, we observed neutrophil recruitment accompanied by induction of KC, macrophage inflammatory protein 2 (MIP-2), NOS-2, interleukin-6 (IL-6), and IL-17a. Pups suckled by an immunized dam did not mount this response. Accessory toxins RtxA and HlyA played no discernible role in neutrophil recruitment in a wild-type background. The innate response to
V. cholerae
deleted for cholera toxin-encoding phage (CTXϕ) and part of
rtxA
was significantly reduced, suggesting a role for CTXϕ-carried genes or for RtxA in the absence of cholera toxin (CTX). Two extracellular
V. cholerae
DNases were not required for neutrophil recruitment, but DNase-deficient
V. cholerae
caused more clouds of DNA in the intestinal lumen, which appeared to be neutrophil extracellular traps (NETs), suggesting that
V. cholerae
DNases combat NETs. Thus, the infant mouse model has hitherto unrecognized utility for interrogating innate responses to
V. cholerae
infection.
Functional Antibodies against VAR2CSA in Nonpregnant Populations from Colombia Exposed to Plasmodium falciparum and Plasmodium vivax
Authors: Gnidehou Sedami , Doritchamou Justin , Arango Eliana M. , Cabrera Ana , Arroyo Maria Isabel , Kain Kevin C. , Ndam Nicaise Tuikue , Maestre Amanda , Yanow Stephanie K. 
Published: April 2014

ABSTRACT

In pregnancy, parity-dependent immunity is observed in response to placental infection with
Plasmodium falciparum
. Antibodies recognize the surface antigen, VAR2CSA, expressed on infected red blood cells and inhibit cytoadherence to the placental tissue. In most settings of malaria endemicity, antibodies against VAR2CSA are predominantly observed in multigravid women and infrequently in men, children, and nulligravid women. However, in Colombia, we detected antibodies against multiple constructs of VAR2CSA among men and children with acute
P. falciparum
and
Plasmodium vivax
infection. The majority of men and children (>60%) had high levels of IgGs against three recombinant domains of VAR2CSA: DBL5ε, DBL3X, and ID1-ID2. Surprisingly, these antibodies were observed only in pregnant women, men, and children exposed either to
P. falciparum
or to
P. vivax
. Moreover, the anti-VAR2CSA antibodies are of high avidity and efficiently inhibit adherence of infected red blood cells to chondroitin sulfate A
in vitro
, suggesting that they are specific and functional. These unexpected results suggest that there may be genotypic or phenotypic differences in the parasites of this region or in the host response to either
P. falciparum
or
P. vivax
infection outside pregnancy. These findings may hold significant clinical relevance to the pathophysiology and outcome of malaria infections in this region.
Novel Pneumocystis Antigen Discovery Using Fungal Surface Proteomics
Authors: Zheng Mingquan , Cai Yang , Eddens Taylor , Ricks David M. , Kolls Jay K. 
Published: April 2014

ABSTRACT

Pneumonia due to the fungus
Pneumocystis jirovecii
is a life-threatening infection that occurs in immunocompromised patients. The inability to culture the organism as well as the lack of an annotated genome has hindered antigen discovery that could be useful in developing novel vaccine- or antibody-based therapies as well as diagnostics for this infection. Here we report a novel method of surface proteomics analysis of
Pneumocystis murina
that reliably detected putative surface proteins that are conserved in
Pneumocystis jirovecii
. This technique identified novel CD4
+
T-cell epitopes as well as a novel B-cell epitope, Meu10, which encodes a glycosylphosphatidylinositol (GPI)-anchored protein thought to be involved in ascospore assembly. The described technique should facilitate the discovery of novel target proteins for diagnostics and therapeutics for
Pneumocystis
infection.
A Putative Regulatory Genetic Locus Modulates Virulence in the Pathogen Leptospira interrogans
Authors: Eshghi Azad , Becam Jérôme , Lambert Ambroise , Sismeiro Odile , Dillies Marie-Agnès , Jagla Bernd , Wunder Elsio A. , Ko Albert I. , Coppee Jean-Yves , Goarant Cyrille , Picardeau Mathieu 
Published: April 2014

ABSTRACT

Limited research has been conducted on the role of transcriptional regulators in relation to virulence in
Leptospira interrogans
, the etiological agent of leptospirosis. Here, we identify an
L. interrogans
locus that encodes a sensor protein, an anti-sigma factor antagonist, and two genes encoding proteins of unknown function. Transposon insertion into the gene encoding the sensor protein led to dampened transcription of the other 3 genes in this locus. This lb139 insertion mutant (the lb139
−
mutant) displayed attenuated virulence in the hamster model of infection and reduced motility
in vitro
. Whole-transcriptome analyses using RNA sequencing revealed the downregulation of 115 genes and the upregulation of 28 genes, with an overrepresentation of gene products functioning in motility and signal transduction and numerous gene products with unknown functions, predicted to be localized to the extracellular space. Another significant finding encompassed suppressed expression of the majority of the genes previously demonstrated to be upregulated at physiological osmolarity, including the sphingomyelinase C precursor Sph2 and LigB. We provide insight into a possible requirement for transcriptional regulation as it relates to leptospiral virulence and suggest various biological processes that are affected due to the loss of native expression of this genetic locus.
Read-Performance Optimization for Deduplication-Based Storage Systems in the Cloud
Authors: Mao Bo , Jiang Hong , Wu Suzhen , Fu Yinjin , Tian Lei 
Published: April 2014

Data deduplication has been demonstrated to be an effective technique in reducing the total data transferred over the network and the storage space in cloud backup, archiving, and primary storage systems, such as VM (virtual machine) platforms. However, the performance of restore operations from a deduplicated backup can be significantly lower than that without deduplication. The main reason lies in the fact that a file or block is split into multiple small data chunks that are often located in different disks after deduplication, which can cause a subsequent read operation to invoke many disk IOs involving multiple disks and thus degrade the read performance significantly. While this problem has been by and large ignored in the literature thus far, we argue that the time is ripe for us to pay significant attention to it in light of the emerging cloud storage applications and the increasing popularity of the VM platform in the cloud. This is because, in a cloud storage or VM environment, a simple read request on the client side may translate into a restore operation if the data to be read or a VM suspended by the user was previously deduplicated when written to the cloud or the VM storage server, a likely scenario considering the network bandwidth and storage capacity concerns in such an environment.
To address this problem, in this article, we propose SAR, an SSD (solid-state drive)-Assisted Read scheme, that effectively exploits the high random-read performance properties of SSDs and the unique data-sharing characteristic of deduplication-based storage systems by storing in SSDs the unique data chunks with high reference count, small size, and nonsequential characteristics. In this way, many read requests to HDDs are replaced by read requests to SSDs, thus significantly improving the read performance of the deduplication-based storage systems in the cloud. The extensive trace-driven and VM restore evaluations on the prototype implementation of SAR show that SAR outperforms the traditional deduplication-based and flash-based cache schemes significantly, in terms of the average response times.
Efficient hosted interpreters on the JVM
Authors: Savrun-Yeniçeri Gülfem , Zhang Wei , Zhang Huahan , Seckler Eric , Li Chen , Brunthaler Stefan , Larsen Per , Franz Michael 
Published: April 2014

Many guest languages are implemented using the Java Virtual Machine (JVM) as a host environment. There are two major implementation choices: custom compilers and so-called hosted interpreters. Custom compilers are complex to build but offer good performance. Hosted interpreters are comparatively simpler to implement but until now have suffered from poor performance.
We studied the performance of hosted interpreters and identified common bottlenecks preventing their efficient execution. First, similar to interpreters written in C/C++, instruction dispatch is expensive on the JVM. Second, Java’s semantics require expensive runtime exception checks that negatively affect array performance essential to interpreters.
We present two optimizations targeting these bottlenecks and show that the performance of optimized interpreters increases dramatically: we report speedups by a factor of up to 2.45 over the Jython interpreter, 3.57 over the Rhino interpreter, and 2.52 over the JRuby interpreter, respectively. The resulting performance is comparable with that of custom compilers. Our optimizations are enabled by a few simple annotations that require only modest implementation effort; in return, performance increases substantially.
How to Improve Your Search Engine Ranking
Authors: Su Ao-Jan , Hu Y. Charlie , Kuzmanovic Aleksandar , Koh Cheng-Kok 
Published: April 2014

Search engines have greatly influenced the way people access information on the Internet, as such engines provide the preferred entry point to billions of pages on the Web. Therefore, highly ranked Web pages generally have higher visibility to people and pushing the ranking higher has become the top priority for Web masters. As a matter of fact, Search Engine Optimization (SEO) has became a sizeable business that attempts to improve their clients’ ranking. Still, the lack of ways to validate SEO’s methods has created numerous myths and fallacies associated with ranking algorithms.
In this article, we focus on two ranking algorithms, Google’s and Bing’s, and design, implement, and evaluate a ranking system to systematically validate assumptions others have made about these popular ranking algorithms. We demonstrate that linear learning models, coupled with a recursive partitioning ranking scheme, are capable of predicting ranking results with high accuracy. As an example, we manage to correctly predict 7 out of the top 10 pages for 78% of evaluated keywords. Moreover, for content-only ranking, our system can correctly predict 9 or more pages out of the top 10 ones for 77% of search terms. We show how our ranking system can be used to reveal the relative importance of ranking features in a search engine’s ranking function, provide guidelines for SEOs and Web masters to optimize their Web pages, validate or disprove new ranking features, and evaluate search engine ranking results for possible ranking bias.
On Third-Order Nonlinearity of Biquadratic Monomial Boolean Functions
Authors: Singh Brajesh Kumar 
Published: April 2014

The rth-order nonlinearity of Boolean function plays a central role against several known attacks on stream and block ciphers. Because of the fact that its maximum equals the covering radius of the rth-order Reed-Muller code, it also plays an important role in coding theory. The computation of exact value or high lower bound on the rth-order nonlinearity of a Boolean function is very complicated problem, especially when r>1. This paper is concerned with the computation of the lower bounds for third-order nonlinearities of two classes of Boolean functions of the form Tr1nλxd for all x∈𝔽2n, λ∈𝔽2n*, where a d=2i+2j+2k+1, where i, j, and k are integers such that i>j>k≥1 and n>2i, and b d=23ℓ+22ℓ+2ℓ+1, where ℓ is a positive integer such that gcdℓ,𝓃=1 and n>6.
Intratumoral Immunization: A New Paradigm for Cancer Therapy
Authors: Marabelle Aurélien , Kohrt Holbrook , Caux Christophe , Levy Ronald 
Published: April 2014

AbstractImmune cell infiltration in the tumor microenvironment is of prognostic and therapeutic import. These immune cell subsets can be heterogeneous and are composed of mature antigen-presenting cells, helper and effector cytotoxic T cells, toleragenic dendritic cells, tumor-associated macrophages, and regulatory T cells, among other cell types. With the development of novel drugs that target the immune system rather than the cancer cells, the tumor immune microenvironment is not only prognostic for overall patient outcome, but also predictive for likelihood of response to these immune-targeted therapies. Such therapies aim to reverse the cancer immunotolerance and trigger an effective antitumor immune response. Two major families of immunostimulatory drugs are currently in clinical development: pattern recognition receptor agonists (PRRago) and immunostimulatory monoclonal antibodies (ISmAb). Despite their immune-targeted design, these agents have so far been developed clinically as if they were typical anticancer drugs. Here, we review the limitations of this conventional approach, specifically addressing the shortcomings of the usual schedules of intravenous infusions every 2 or 3 weeks. If the new modalities of immunotherapy target specific immune cells within the tumor microenvironment, it might be preferable to deliver them locally into the tumor rather than systemically. There is preclinical and clinical evidence that a therapeutic systemic antitumor immune response can be generated upon intratumoral immunomodulation. Moreover, preclinical results have shown that therapeutic synergy can be obtained by combining PRRagos and ISmAbs to the local tumor site. Clin Cancer Res; 20(7); 1747–56. ©2014 AACR.
A Panel of Three Markers Hyper- and Hypomethylated in Urine Sediments Accurately Predicts Bladder Cancer Recurrence
Authors: Su Sheng-Fang , de Castro Abreu André Luís , Chihara Yoshitomo , Tsai Yvonne , Andreu-Vieyra Claudia , Daneshmand Siamak , Skinner Eila C. , Jones Peter A. , Siegmund Kimberly D. , Liang Gangning 
Published: April 2014

Abstract
Purpose: The high risk of recurrence after transurethral resection of bladder tumor of nonmuscle invasive disease requires lifelong treatment and surveillance. Changes in DNA methylation are chemically stable, occur early during tumorigenesis, and can be quantified in bladder tumors and in cells shed into the urine. Some urine markers have been used to help detect bladder tumors; however, their use in longitudinal tumor recurrence surveillance has yet to be established.
Experimental Design: We analyzed the DNA methylation levels of six markers in 368 urine sediment samples serially collected from 90 patients with noninvasive urothelial carcinoma (Tis, Ta, T1; grade low-high). The optimum marker combination was identified using logistic regression with 5-fold cross-validation, and validated in separate samples.
Results: A panel of three markers discriminated between patients with and without recurrence with the area under the curve of 0.90 [95% confidence interval (CI), 0.86–0.92] and 0.95 (95% CI, 0.90–1.00), sensitivity and specificity of 86%/89% (95% CI, 74%–99% and 81%–97%) and 80%/97% (95% CI, 60%–96% and 91%–100%) in the testing and validation sets, respectively. The three-marker DNA methylation test reliably predicted tumor recurrence in 80% of patients superior to cytology (35%) and cystoscopy (15%) while accurately forecasting no recurrence in 74% of patients that scored negative in the test.
Conclusions: Given their superior sensitivity and specificity in urine sediments, a combination of hyper- and hypomethylated markers may help avoid unnecessary invasive exams and reveal the importance of DNA methylation in bladder tumorigenesis. Clin Cancer Res; 20(7); 1978–89. ©2014 AACR.
Speaking of Other Animals
Authors: Beauclair Alain 
Published: April 2014

Abstract
Commonly ignored on the issue, Hans-Georg Gadamer’s contribution to the question of other animals is analyzed in this paper. Focusing on Gadamer’s phenomenological account of language and drawing from his Aristotelian and Heideggerian roots, I argue that Gadamer draws a path toward a novel reconsideration of the difference between the living and human essences, a reconsideration that brings us to the limits of λόγος and resolves itself in the ontological concept of play.
Influence of Subfacet Heterogeneity and Material Properties on the Urban Surface Energy Budget
Authors: Ramamurthy Prathap , Bou-Zeid Elie , Smith James A. , Wang Zhihua , Baeck Mary L. , Saliendra Nicanor Z. , Hom John L. , Welty Claire 
Published: March 2014

AbstractUrban facets—the walls, roofs, and ground in built-up terrain—are often conceptualized as homogeneous surfaces, despite the obvious variability in the composition and material properties of the urban fabric at the subfacet scale. This study focuses on understanding the influence of this subfacet heterogeneity, and the associated influence of different material properties, on the urban surface energy budget. The Princeton Urban Canopy Model, which was developed with the ability to capture subfacet variability, is evaluated at sites of various building densities and then applied to simulate the energy exchanges of each subfacet with the atmosphere over a densely built site. The analyses show that, although all impervious built surfaces convert most of the incoming energy into sensible heat rather than latent heat, sensible heat fluxes from asphalt pavements and dark rooftops are 2 times as high as those from concrete surfaces and light-colored roofs. Another important characteristic of urban areas—the shift in the peak time of sensible heat flux in comparison with rural areas—is here shown to be mainly linked to concrete’s high heat storage capacity as well as to radiative trapping in the urban canyon. The results also illustrate that the vegetated pervious soil surfaces that dot the urban landscape play a dual role: during wet periods they redistribute much of the available energy into evaporative fluxes but when moisture stressed they behave more like an impervious surface. This role reversal, along with the direct evaporation of water stored over impervious surfaces, significantly reduces the overall Bowen ratio of the urban site after rain events.
Impact of a novel online learning module on specialist palliative care nurses’ pain assessment competencies and patients’ reports of pain: Results from a quasi-experimental pilot study
Authors: Phillips Jane L , Heneka Nicole , Hickman Louise , Lam Lawrence , Shaw Tim 
Published: April 2014

Background: Pain is a complex multidimensional phenomenon moderated by consumer, provider and health system factors. Effective pain management cuts across professional boundaries, with failure to screen and assess contributing to the burden of unrelieved pain. Aim: To test the impact of an online pain assessment learning module on specialist palliative care nurses’ pain assessment competencies, and to determine whether this education impacted positively on palliative care patients’ reported pain ratings. Design: A quasi-experimental pain assessment education pilot study utilising ‘Qstream©’, an online methodology to deliver 11 case-based pain assessment learning scenarios, developed by an interdisciplinary expert panel and delivered to participants’ work emails over a 28-day period in mid-2012. The ‘Self-Perceived Pain Assessment Competencies’ survey and chart audit data, including patient-reported pain intensity ratings, were collected pre-intervention (T1) and post-intervention (T2) and analysed using inferential statistics to determine key outcomes. Setting/participants: Nurses working at two Australian inpatient specialist palliative care services in 2012. Results: The results reported conform to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Guidelines. Participants who completed the education intervention ( n = 34) increased their pain assessment knowledge, assessment tool knowledge and confidence to undertake a pain assessment ( p < 0.001). Participants were more likely to document pain intensity scores in patients’ medical records than non-participants (95% confidence interval = 7.3%–22.7%, p = 0.021). There was also a significant reduction in the mean patient-reported pain ratings between the admission and audit date at post-test of 1.5 (95% confidence interval = 0.7–2.3) units in pain score. Conclusion: This pilot confers confidence of the education interventions capacity to improve specialist palliative care nurses’ pain assessment practices and to reduce patient-rated pain intensity scores.
Composing multiple StarPU applications over heterogeneous machines: A supervised approach
Authors: Hugo Andra , Guermouche Abdou , Wacrenier Pierre-André , Namyst Raymond 
Published: April 2014

Enabling HPC applications to perform efficiently when invoking multiple parallel libraries simultaneously is a great challenge. Even if a uniform runtime system is used underneath, scheduling tasks or threads coming from different libraries over the same set of hardware resources introduces many issues, such as resource oversubscription, undesirable cache flushes and memory bus contention. This paper presents an extension of StarPU, a runtime system specifically designed for heterogeneous architectures, that allows multiple parallel codes to run concurrently with minimal interference. Such parallel codes run within scheduling contexts that provide confined execution environments which can be used to partition computing resources. Scheduling contexts can be dynamically resized to optimize the allocation of computing resources among concurrently running libraries. We introduce a hypervisor that automatically expands or shrinks contexts using feedback from the runtime system (e.g. resource utilization). We demonstrate the relevance of our approach using benchmarks invoking multiple high performance linear algebra kernels simultaneously on top of heterogeneous multicore machines. We show that our mechanism can dramatically improve the overall application run time (− 34%), most notably by reducing the average cache miss ratio (− 50%).