bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-7 Produced by Intestinal Epithelial Cells in Response to Citrobacter rodentium Infection Plays a Major Role in Innate Immunity against This Pathogen
Authors: Zhang Wei , Du Jiang-Yuan , Yu Qing , Jin Jun-O 
Published: June 2015

ABSTRACT

Interleukin-7 (IL-7) engages multiple mechanisms to overcome chronic viral infections, but the role of IL-7 in bacterial infections, especially enteric bacterial infections, remains unclear. Here we characterized the previously unexplored role of IL-7 in the innate immune response to the attaching and effacing bacterium
Citrobacter rodentium
.
C. rodentium
infection induced IL-7 production from intestinal epithelial cells (IECs). IL-7 production from IECs in response to
C. rodentium
was dependent on gamma interferon (IFN-γ)-producing NK1.1
+
cells and IL-12. Treatment with anti-IL-7Rα antibody during
C. rodentium
infection resulted in a higher bacterial burden, enhanced intestinal damage, and greater weight loss and mortality than observed with the control IgG treatment. IEC-produced IL-7 was only essential for protective immunity against
C. rodentium
during the first 6 days after infection. An impaired bacterial clearance upon IL-7Rα blockade was associated with a significant decrease in macrophage accumulation and activation in the colon. Moreover,
C. rodentium
-induced expansion and activation of intestinal CD4
+
lymphoid tissue inducer (LTi) cells was completely abrogated by IL-7Rα blockade. Collectively, these data demonstrate that IL-7 is produced by IECs in response to
C. rodentium
infection and plays a critical role in the protective immunity against this intestinal attaching and effacing bacterium.
Microinjection of Francisella tularensis and Listeria monocytogenes Reveals the Importance of Bacterial and Host Factors for Successful Replication
Authors: Meyer Lena , Bröms Jeanette E. , Liu Xijia , Rottenberg Martin E. , Sjöstedt Anders 
Published: June 2015

ABSTRACT

Certain intracellular bacteria use the host cell cytosol as the replicative niche. Although it has been hypothesized that the successful exploitation of this compartment requires a unique metabolic adaptation, supportive evidence is lacking. For
Francisella tularensis
, many genes of the
Francisella
pathogenicity island (FPI) are essential for intracellular growth, and therefore, FPI mutants are useful tools for understanding the prerequisites of intracytosolic replication. We compared the growth of bacteria taken up by phagocytic or nonphagocytic cells with that of bacteria microinjected directly into the host cytosol, using the live vaccine strain (LVS) of
F. tularensis
; five selected FPI mutants thereof, i.e., Δ
iglA
, Δ
iglC
̧ Δ
iglG
, Δ
iglI
, and Δ
pdpE
strains; and
Listeria monocytogenes
. After uptake in bone marrow-derived macrophages (BMDM), ASC
−/−
BMDM, MyD88
−/−
BMDM, J774 cells, or HeLa cells, LVS, Δ
pdpE
and Δ
iglG
mutants, and
L. monocytogenes
replicated efficiently in all five cell types, whereas the Δ
iglA
and Δ
iglC
mutants showed no replication. After microinjection, all 7 strains showed effective replication in J774 macrophages, ASC
−/−
BMDM, and HeLa cells. In contrast to the rapid replication in other cell types,
L. monocytogenes
showed no replication in MyD88
−/−
BMDM and LVS showed no replication in either BMDM or MyD88
−/−
BMDM after microinjection. Our data suggest that the mechanisms of bacterial uptake as well as the permissiveness of the cytosolic compartment
per se
are important factors for the intracytosolic replication. Notably, none of the investigated FPI proteins was found to be essential for intracytosolic replication after microinjection.
A cross-sectional study on upright heart rate and BP changing characteristics: basic data for establishing diagnosis of postural orthostatic tachycardia syndrome and orthostatic hypertension
Authors: Zhao Juan , Han Zhenhui , Zhang Xi , Du Shuxu , Liu Angie Dong , Holmberg Lukas , Li Xueying , Lin Jing , Xiong Zhenyu , Gai Yong , Yang Jinyan , Liu Ping , Tang Chaoshu , Du Junbao , Jin Hongfang 
Published: June 2015

ObjectiveWe aimed to determine upright heart rate and blood pressure (BP) changes to suggest diagnostic criteria for postural orthostatic tachycardia syndrome (POTS) and orthostatic hypertension (OHT) in Chinese children.MethodsIn this cross-sectional study, 1449 children and adolescents aged 6–18 years were randomly recruited from two cities in China, Kaifeng in Henan province and Anguo in Hebei province. They were divided into two groups: 844 children aged 6–12 years (group I) and 605 adolescents aged 13–18 years (group II). Heart rate and BP were recorded during an active standing test.Results95th percentile (P95) of δ heart rate from supine to upright was 38 bpm, with a maximum upright heart rate of 130 and 124 bpm in group I and group II, respectively. P95of δ systolic blood pressure (SBP) increase was 18 mm Hg and P95of upright SBP was 132 mm Hg in group I and 138 mm Hg in group II. P95of δ diastolic blood pressure (DBP) increase was 24 mm Hg in group I and 21 mm Hg in group II, and P95of upright DBP was 89 mm Hg in group I and 91 mm Hg in group II.ConclusionsPOTS is suggested when δ heart rate is ≥38 bpm (for easy memory, ≥40 bpm) from supine to upright, or maximum heart rate ≥130 bpm (children aged 6–12 years) and ≥125 bpm (adolescents aged 13–18 years), associated with orthostatic symptoms. OHT is suggested when δ SBP (increase) is ≥20 mm Hg, and/or δ DBP (increase) ≥25 mm Hg (in children aged 6–12 years) or ≥20 mm Hg (in adolescents aged 13–18 years) from supine to upright; or upright BP≥130/90 mm Hg (in children aged 6–12 years) or ≥140/90 mm Hg (in adolescents aged 13–18 years).
A prospective study of adverse drug reactions to antiepileptic drugs in children
Authors: Anderson Mark , Egunsola Oluwaseun , Cherrill Janine , Millward Claire , Fakis Apostolos , Choonara Imti 
Published: June 2015

ObjectivesTo prospectively determine the nature and rate of adverse drug reactions (ADRs) in children on antiepileptic drugs (AEDs) and to prospectively evaluate the effect of AEDs on behaviour.SettingA single centre prospective observational study.ParticipantsChildren (<18 years old) receiving one or more AEDs for epilepsy, at each clinically determined follow-up visit.Primary and secondary outcomesPrimary outcome was adverse reactions of AEDs. Behavioural and cognitive functions were secondary outcomes.Results180 children were recruited. Sodium valproate and carbamazepine were the most frequently used AEDs. A total of 114 ADRs were recorded in 56 of these children (31%). 135 children (75%) were on monotherapy. 27 of the 45 children (60%) on polytherapy had ADRs; while 29 (21%) of those on monotherapy had ADRs. The risk of ADRs was significantly lower in patients receiving monotherapy than polytherapy (RR: 0.61, 95% CI 0.47 to 0.79, p<0.0001). Behavioural problems and somnolence were the most common ADRs. 23 children had to discontinue their AED due to an ADR.ConclusionsBehavioural problems and somnolence were the most common ADRs. Polytherapy significantly increases the likelihood of ADRs in children.Trail registration numberEudraCT (2007-000565-37).
Factors associated with pregnancy among adolescents in low-income and lower middle-income countries: a systematic review
Authors: Pradhan Rina , Wynter Karen , Fisher Jane 
Published: June 2015

BackgroundPregnancy-related morbidity and mortality is much more prevalent among adolescents than adults. Adolescent pregnancy is therefore a significant public health problem. Most births to adolescents (95%) occur in resource-constrained countries.ObjectiveThe aim was to review the available evidence about the factors associated with adolescent pregnancy in low-income and lower middle-income countries.MethodsThe review used the PRISMA procedure of identification, screening and eligibility of publications. PubMed, OVID MEDLINE, SCOPUS and CINAHL plus were searched systematically for peer-reviewed English language papers published before December 2013.FindingsIn total, 2005 articles were identified and 12 met the inclusion criteria and were reviewed. Despite varied methods, there was substantial consistency in the findings. Limited education, low socioeconomic position, insufficient access to and non-use of contraception were consistently found to be risks for pregnancy among adolescents. There was some evidence that early marriage, living in a rural area, early sexual initiation, belonging to an ethnic and religious minority group also increased the risk of adolescent pregnancy. Higher education, access to income-generating work and family support were found to protect against adolescent pregnancy.ConclusionsIn resource-constrained countries, as in well-resourced countries, low socioeconomic position appears to increase the risk of pregnancy among adolescents. Additional risks specific to these contexts include cultural traditions such as early marriage and inaccurate beliefs about contraception. It is unlikely that strategies to reduce pregnancy among women aged less than 20 years will be effective unless these are addressed directly.
Increasing active travel: results of a quasi-experimental study of an intervention to encourage walking and cycling
Authors: Keall Michael , Chapman Ralph , Howden-Chapman Philippa , Witten Karen , Abrahamse Wokje , Woodward Alistair 
Published: June 2015

BackgroundThere is increased interest in the effectiveness and cobenefits of measures to promote walking and cycling, including health gains from increased physical activity and reductions in fossil fuel use and vehicle emissions. This paper analyses the changes in walking and cycling in two New Zealand cities that accompanied public investment in infrastructure married with programmes to encourage active travel.MethodUsing a quasi-experimental two-group pre–post study design, we estimated changes in travel behaviour from baseline in 2011 to mid-programme in 2012, and postprogramme in 2013. The intervention and control cities were matched in terms of sociodemographic variables and baseline levels of walking and cycling. A face-to-face survey obtained information on walking and cycling. We also drew from the New Zealand Travel Survey, a national ongoing survey of travel behaviour, which was conducted in the study areas. Estimates from the two surveys were combined using meta-analysis techniques.ResultsThe trips and physical activity were evaluated. Relative to the control cities, the odds of trips being by active modes (walking or cycling) increased by 37% (95% CI 8% to 73%) in the intervention cities between baseline and postintervention. The net proportion of trips made by active modes increased by about 30%. In terms of physical activity levels, there was little evidence of an overall change.DiscussionComparing the intervention cities with the matched controls, we found substantial changes in walking and cycling, and conclude that the improvements in infrastructure and associated programmes appear to have successfully arrested the general decline in active mode use evident in recent years.
Hyperthermia and hypercapnia following two intravenous injections of atracurium in a dog
Authors: Rigotti Clara , Dugdale Alex , Alderson Briony 
Published: June 2015

A three month old, 5 kg American Bulldog presented with severe dyspnoea and cyanosis seven hours after being submerged in a fresh‐water paddling pool. Oxygen was supplemented using an oxygen cage, but due to worsening of the clinical signs anaesthesia was induced with 2 mg/kg of propofol and the dog's trachea was intubated. Anaesthesia was maintained with a propofol infusion and mechanical ventilation was provided with 100 per cent inspired oxygen. As the patient was consistently hypercapnic and breathing against the ventilator, atracurium was administered intravenously at 0.2 mg/kg but five minutes later, the dog became hyperthermic (40°C) and hypercapnia drastically worsened. The hyperthermia and hypercapnia slowly resolved to pre‐atracurium values with active cooling. After three hours another dose of atracurium was administered and a similar hyperthermic and hypercapnic reaction developed. Due to the inability to effectively ventilate the lungs and the poor prognosis the owners elected for euthanasia.
Hierarchical model of the actomyosin molecular motor based on ultrametric diffusion with drift
Authors: Khrennikov Andrei , Kozyrev Sergei , Månsson Alf 
Published: June 2015

We discuss the approach to investigate molecular machines using systems of integro–differential ultrametric (p-adic) reaction–diffusion equations with drift. This approach combines the features of continuous and discrete dynamic models. We apply this model to investigation of actomyosin molecular motor. The introduced system of equations is solved analytically using p-adic wavelet theory. We find explicit stationary solutions and behavior in the relaxation regime.
Sirius
Authors: Hauswald Johann , Laurenzano Michael A. , Zhang Yunqi , Li Cheng , Rovinski Austin , Khurana Arjun , Dreslinski Ronald G. , Mudge Trevor , Petrucci Vinicius , Tang Lingjia , Mars Jason 
Published: June 2015

As user demand scales for intelligent personal assistants (IPAs) such as Apple's Siri, Google's Google Now, and Microsoft's Cortana, we are approaching the computational limits of current datacenter architectures. It is an open question how future server architectures should evolve to enable this emerging class of applications, and the lack of an open-source IPA workload is an obstacle in addressing this question. In this paper, we present the design of Sirius, an open end-to-end IPA web-service application that accepts queries in the form of voice and images, and responds with natural language. We then use this workload to investigate the implications of four points in the design space of future accelerator-based server architectures spanning traditional CPUs, GPUs, manycore throughput co-processors, and FPGAs.
To investigate future server designs for Sirius, we decompose Sirius into a suite of 7 benchmarks (Sirius Suite) comprising the computationally intensive bottlenecks of Sirius. We port Sirius Suite to a spectrum of accelerator platforms and use the performance and power trade-offs across these platforms to perform a total cost of ownership (TCO) analysis of various server design points. In our study, we find that accelerators are critical for the future scalability of IPA services. Our results show that GPU- and FPGA-accelerated servers improve the query latency on average by 10x and 16x. For a given throughput, GPU- and FPGA-accelerated servers can reduce the TCO of datacenters by 2.6x and 1.4x, respectively.
PuDianNao
Authors: Liu Daofu , Chen Tianshi , Liu Shaoli , Zhou Jinhong , Zhou Shengyuan , Teman Olivier , Feng Xiaobing , Zhou Xuehai , Chen Yunji 
Published: June 2015

Machine Learning (ML) techniques are pervasive tools in various emerging commercial applications, but have to be accommodated by powerful computer systems to process very large data. Although general-purpose CPUs and GPUs have provided straightforward solutions, their energy-efficiencies are limited due to their excessive supports for flexibility. Hardware accelerators may achieve better energy-efficiencies, but each accelerator often accommodates only a single ML technique (family). According to the famous No-Free-Lunch theorem in the ML domain, however, an ML technique performs well on a dataset may perform poorly on another dataset, which implies that such accelerator may sometimes lead to poor learning accuracy. Even if regardless of the learning accuracy, such accelerator can still become inapplicable simply because the concrete ML task is altered, or the user chooses another ML technique.In this study, we present an ML accelerator called PuDianNao, which accommodates seven representative ML techniques, including k-means, k-nearest neighbors, naive bayes, support vector machine, linear regression, classification tree, and deep neural network. Benefited from our thorough analysis on computational primitives and locality properties of different ML techniques, PuDianNao can perform up to 1056 GOP/s (e.g., additions and multiplications) in an area of 3.51 mm^2, and consumes 596 mW only. Compared with the NVIDIA K20M GPU (28nm process), PuDianNao (65nm process) is 1.20x faster, and can reduce the energy by 128.41x.
Beyond the PDP-11
Authors: Chisnall David , Rothwell Colin , Watson Robert N.M. , Woodruff Jonathan , Vadera Munraj , Moore Simon W. , Roe Michael , Davis Brooks , Neumann Peter G. 
Published: June 2015

We propose a new memory-safe interpretation of the C abstract machine that provides stronger protection to benefit security and debugging. Despite ambiguities in the specification intended to provide implementation flexibility, contemporary implementations of C have converged on a memory model similar to the PDP-11, the original target for C. This model lacks support for memory safety despite well-documented impacts on security and reliability.
Attempts to change this model are often hampered by assumptions embedded in a large body of existing C code, dating back to the memory model exposed by the original C compiler for the PDP-11. Our experience with attempting to implement a memory-safe variant of C on the CHERI experimental microprocessor led us to identify a number of problematic idioms. We describe these as well as their interaction with existing memory safety schemes and the assumptions that they make beyond the requirements of the C specification. Finally, we refine the CHERI ISA and abstract model for C, by combining elements of the CHERI capability model and fat pointers, and present a softcore CPU that implements a C abstract machine that can run legacy C code with strong memory protection guarantees.
Supporting Differentiated Services in Computers via Programmable Architecture for Resourcing-on-Demand (PARD)
Authors: Ma Jiuyue , Sui Xiufeng , Sun Ninghui , Li Yupeng , Yu Zihao , Huang Bowen , Xu Tianni , Yao Zhicheng , Chen Yun , Wang Haibin , Zhang Lixin , Bao Yungang 
Published: June 2015

This paper presents PARD, a programmable architecture for resourcing-on-demand that provides a new programming interface to convey an application's high-level information like quality-of-service requirements to the hardware. PARD enables new functionalities like fully hardware-supported virtualization and differentiated services in computers. PARD is inspired by the observation that a computer is inherently a network in which hardware components communicate via packets (e.g., over the NoC or PCIe). We apply principles of software-defined networking to this intra-computer network and address three major challenges. First, to deal with the semantic gap between high-level applications and underlying hardware packets, PARD attaches a high-level semantic tag (e.g., a virtual machine or thread ID) to each memory-access, I/O, or interrupt packet. Second, to make hardware components more manageable, PARD implements programmable control planes that can be integrated into various shared resources (e.g., cache, DRAM, and I/O devices) and can differentially process packets according to tag-based rules. Third, to facilitate programming, PARD abstracts all control planes as a device file tree to provide a uniform programming interface via which users create and apply tag-based rules.
Full-system simulation results show that by co-locating latencycritical memcached applications with other workloads PARD can improve a four-core computer's CPU utilization by up to a factor of four without significantly increasing tail latency. FPGA emulation based on a preliminary RTL implementation demonstrates that the cache control plane introduces no extra latency and that the memory control plane can reduce queueing delay for high-priority memory-access requests by up to a factor of 5.6.
GPU Concurrency
Authors: Alglave Jade , Batty Mark , Donaldson Alastair F. , Gopalakrishnan Ganesh , Ketema Jeroen , Poetzl Daniel , Sorensen Tyler , Wickerson John 
Published: June 2015

Concurrency is pervasive and perplexing, particularly on graphics processing units (GPUs). Current specifications of languages and hardware are inconclusive; thus programmers often rely on folklore assumptions when writing software.
To remedy this state of affairs, we conducted a large empirical study of the concurrent behaviour of deployed GPUs. Armed with litmus tests (i.e. short concurrent programs), we questioned the assumptions in programming guides and vendor documentation about the guarantees provided by hardware. We developed a tool to generate thousands of litmus tests and run them under stressful workloads. We observed a litany of previously elusive weak behaviours, and exposed folklore beliefs about GPU programming---often supported by official tutorials---as false.
As a way forward, we propose a model of Nvidia GPU hardware, which correctly models every behaviour witnessed in our experiments. The model is a variant of SPARC Relaxed Memory Order (RMO), structured following the GPU concurrency hierarchy.
SLFN11: Achilles' Heel or Troublemaker
Authors: Kovar Heinrich 
Published: June 2015

Abstract
SLFN11 expression correlates with sensitivity of tumors to topoisomerase and DNA-targeting drugs and consequently with prognosis. Regulation of SLFN11 by ETS factors opens new avenues to treatment optimization, maximizing antitumor activity and minimizing adverse side effects. Interrogating drug-induced gene expression signatures for SLFN11 modulations may affect the design of therapeutic regimens. Clin Cancer Res; 21(18); 4033–4. ©2015 AACR.
See related article by Tang et al., p. 4184
E2F4 Program Is Predictive of Progression and Intravesical Immunotherapy Efficacy in Bladder Cancer
Authors: Cheng Chao , Varn Frederick S. , Marsit Carmen J. 
Published: June 2015

AbstractBladder cancer is a common malignant disease, with non–muscle-invasive bladder cancer (NMIBC) representing the majority of tumors. This cancer subtype is typically treated by transurethral resection. In spite of treatment, up to 70% of patients show local recurrences. Intravesical BCG (Bacillus Calmette-Guerin) immunotherapy has been widely used to treat NMIBC, but it fails to suppress recurrence of bladder tumors in up to 40% of patients. Therefore, the development of prognostic markers is needed to predict the progression of bladder cancer and the efficacy of intravesical BCG treatment. This study demonstrates the effectiveness of an E2F4 signature for prognostic prediction of bladder cancer. E2F4 scores for each sample in a bladder cancer expression dataset were calculated by summarizing the relative expression levels of E2F4 target genes identified by ChIP-seq, and then the scores were used to stratify patients into good- and poor-outcome groups. The molecular signature was investigated in a single bladder cancer dataset and then its effectiveness was confirmed in two meta-bladder datasets consisting of specimens from multiple independent studies. These results were consistent in different datasets and demonstrate that the E2F4 score is predictive of clinical outcomes in bladder cancer, with patients whose tumors exhibit an E2F4 score &gt;0 having significantly shorter survival times than those with an E2F4 score &lt;0, in both non–muscle-invasive, and muscle-invasive bladder cancer. Furthermore, although intravesical BCG immunotherapy can significantly improve the clinical outcome of NMIBC patients with positive E2F4 scores (E2F4&gt;0 group), it does not show significant treatment effect for those with negative scores (E2F4&lt;0 group).Implications: The E2F4 signature can be applied to predict the progression/recurrence and the responsiveness of patients to intravesical BCG immunotherapy in bladder cancer. Mol Cancer Res; 13(9); 1316–24. ©2015 AACR.