bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Information Asymmetry Matter to Equity Pricing? Evidence from Firms’ Geographic Location*
Authors: El Ghoul Sadok , Guedhami Omrane , Ni Yang , Pittman Jeffrey , Saadi Samir 
Published: October 2011

AbstractThe scarcity of suitable proxies for asymmetric information has impeded empirical research from providing reliable evidence on whether information risk shapes equity pricing. In reexamining this unresolved question, we rely on firms’ geographic distance from financial centers to gauge information asymmetry. We provide strong, robust evidence supporting the prediction that equity financing is cheaper for firms nearer central locations, implying that investors rationally require more compensation when information asymmetry is worse. The equity pricing role of geographic proximity is economically large, with our coefficient estimates translating into firms located within 100 kilometers of the city center of the nearest of six major financial centers, or in their metropolitan statistical areas, enjoying equity financing costs that are seven basis points lower. Our inferences are insensitive to measuring both the cost of equity capital and distance in several ways, controlling for corporate governance quality, and addressing endogeneity. Collectively, our analysis suggests that investors discount the price that they pay for their securities to reflect the greater information asymmetry that ensues when firms are far from major financial centers.
Pharmacodynamics of β-Lactamase Inhibition by NXL104 in Combination with Ceftaroline: Examining Organisms with Multiple Types of β-Lactamases
Authors: Louie Arnold , Castanheira Mariana , Liu Weiguo , Grasso Caroline , Jones Ronald N. , Williams Gregory , Critchley Ian , Thye Dirk , Brown David , VanScoy Brian , Kulawy Robert , Drusano G. L. 
Published: October 2011

ABSTRACT

New broad-spectrum β-lactamases such as KPC enzymes and CTX-M-15 enzymes threaten to markedly reduce the utility of our armamentarium of β-lactam agents, even our most potent drugs, such as carbapenems. NXL104 is a broad-spectrum non-β-lactam β-lactamase inhibitor. In this evaluation, we examined organisms carrying defined β-lactamases and identified doses and schedules of NXL104 in combination with the new cephalosporin ceftaroline, which would maintain good bacterial cell kill and suppress resistance emergence for a clinically relevant period of 10 days in our hollow-fiber infection model. We examined three strains of
Klebsiella pneumoniae
and one isolate of
Enterobacter cloacae. K. pneumoniae
27-908M carried KPC-2, SHV-27, and TEM-1 β-lactamases. Its isogenic mutant,
K. pneumoniae
4207J, was “cured” of the plasmid expressing the KPC-2 enzyme.
K. pneumoniae
24-1318A carried a CTX-M-15 enzyme, and
E. cloacae
2-77C expressed a stably derepressed AmpC chromosomal β-lactamase. Dose-ranging experiments for NXL104 administered as a continuous infusion with ceftaroline at 600 mg every 8 h allowed identification of a 24-h area under the concentration-time curve (AUC) for NXL104 that mediated bactericidal activity and resistance suppression. Dose fractionation experiments identified that “time > threshold” was the pharmacodynamic index linked to cell kill and resistance suppression. Given these results, we conclude that NXL104 combined with ceftaroline on an 8-hourly administration schedule would be optimal for circumstances in which highly resistant pathogens are likely to be encountered. This combination dosing regimen should allow for optimal bacterial cell kill (highest likelihood of successful clinical outcome) and the suppression of resistance emergence.
Lack of Antimicrobial Resistance in Yersinia pestis Isolates from 17 Countries in the Americas, Africa, and Asia
Authors: Urich Sandra K. , Chalcraft Linda , Schriefer Martin E. , Yockey Brook M. , Petersen Jeannine M. 
Published: October 2011

ABSTRACT

Yersinia pestis
is the causative agent of plague, a fulminant disease that is often fatal without antimicrobial treatment. Plasmid (IncA/C)-mediated multidrug resistance in
Y. pestis
was reported in 1995 in Madagascar and has generated considerable public health concern, most recently because of the identification of IncA/C multidrug-resistant plasmids in other zoonotic pathogens. Here, we demonstrate no resistance in 392
Y. pestis
isolates from 17 countries to eight antimicrobials used for treatment or prophylaxis of plague.
Does smoking kill? A study of death certification and smoking
Authors: Proctor Ian , Sharma Vijay , KhoshZaban Mohammad , Winstanley Alison 
Published: October 2011

AimTo assess how frequently smoking is cited as a cause of death (COD) on death certificates.MethodsA retrospective study of 2128 death certificates and 236 postmortem reports issued at a large teaching hospital between 2003 and 2009.ResultsSmoking was identified as the underlying COD on only 2 (0.1%) death certificates and included in part II of the death certificate on 10 (0.5%). The two death certificates citing smoking as the underlying COD were in cases of lung cancer and chronic obstructive pulmonary disease. The study included 279 deaths in which these diagnoses were cited on the death certificate and in the majority of these cases the deceased was a smoker or ex-smoker. A review of postmortem reports from the same period failed to identify a single case in which the pathologist cited smoking as causing or contributing to death. In marked contrast to smoking, 57.4% (vs 0.5%) of death certificates, which included diagnoses linked to alcohol use, cited alcohol in part I of the death certificate.ConclusionThis study demonstrates that smoking is rarely cited on death certificates, even in cases where the causal link with smoking is very strong. There are many reasons why smoking is not cited on death certificates. One frequently cited reason is the reluctance of doctors to stigmatise the deceased. Interestingly, such reluctance did not extend to citing alcohol as a COD. By not recording smoking on death certificates doctors are failing to gather important epidemiological and pathological data.
MANAGING THE CHANGE OF ARCHITECTURE KNOWLEDGE
Authors: SHIBATA TOMOATSU 
Published: October 2011

With the advent of new technologies, one successful case of technological transition is Fanuc Ltd., a company that successfully introduced Intel MPUs (Microprocessor Units) to NC (Numerical Control) machines in 1975 and has since continued to achieve sustained growth. This adoption of MPU caused a change in NC architecture.Through an in-depth case study of Fanuc, we show how adopting MPU to an NC system destroys the usefulness of accumulated hard-wired architectural knowledge in that firm due to changes in architecture. We also show how Fanuc developed the new architectural knowledge necessary for MPU-based soft-wired NC systems. This study is not an analysis of the causes of failure, but rather focuses on the aspects of successful management of architectural change. By analyzing and studying a successful case, we can gain valuable insights into managing architectural knowledge.
Dynamic data folding with parameterizable FPGA configurations
Authors: Bruneel Karel , Heirman Wim , Stroobandt Dirk 
Published: October 2011

In many applications, subsequent data manipulations differ only in a small set of parameter values. Because of their reconfigurability, FPGAs (field programmable gate arrays) can be configured with a specialized circuit each time the parameter values change. This technique is called dynamic data folding. The specialized circuits are smaller and faster than their generic counterparts. However, the overhead involved in generating the configurations for the specialized circuits at runtime is very large when conventional tools are used, and this overhead will in many cases negate the benefit of using optimized configurations.
This article introduces an automatic method for generating runtime parameterizable configurations from arbitrary Boolean circuits. These configurations, in which some of the configuration bits are expressed as a closed-form Boolean expression of a set of parameters, enable very fast run-time specialization, since specialization only involves evaluating these expressions. Our approach is validated on a ternary content-addressable memory (TCAM). We show that the specialized configurations, produced by our method use 2.82 times fewer LUTs than the generic configuration, and even 1.41 times fewer LUTs than the implementation generated by Xilinx Coregen. Moreover, while Coregen needs hand-crafted generators for each type of circuit, our toolflow can be applied to any VHDL design. Using our automatic and generally applicable method, run-time hardware optimization suddenly becomes feasible for a large class of applications.
In support of open reviews; better teaching through large-scale data mining
Authors: Meyer Bertrand , Linden Greg 
Published: October 2011

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

twitter

Follow us on Twitter at http://twitter.com/blogCACM
http://cacm.acm.org/blogs/blog-cacm
Bertrand Meyer writes about his long-standing decision not to provide anonymous reviews. Greg Linden considers how educational practices could be improved through the data mining of students' schoolwork.
Camera Brand Congruence and Camera Model Propagation in the Flickr Social Graph
Authors: Singla Adish , Weber Ingmar 
Published: October 2011

Given that my friends on Flickr use cameras of brand X, am I more likely to also use a camera of brand X? Given that one of these friends changes her brand, am I likely to do the same? Do new camera models pop up uniformly in the friendship graph? Or do early adopters then “convert” their friends? Which factors influence the conversion probability of a user? These are the kind of questions addressed in this work. Direct applications involve personalized advertising in social networks.
For our study, we crawled a complete connected component of the Flickr friendship graph with a total of 67M edges and 3.9M users. 1.2M of these users had at least one public photograph with valid model metadata, which allowed us to assign camera brands and models to users and time slots. Similarly, we used, where provided in a user’s profile, information about a user’s geographic location and the groups joined on Flickr.
Concerning brand congruence, our main findings are the following. First, a pair of friends on Flickr has a higher probability of being congruent, that is, using the same brand, compared to two random users (27% vs. 19%). Second, the degree of congruence goes up for pairs of friends (i) in the same country (29%), (ii) who both only have very few friends (30%), and (iii) with a very high cliqueness (38%). Third, given that a user changes her camera model between March-May 2007 and March-May 2008, high cliqueness friends are more likely than random users to do the same (54% vs. 48%). Fourth, users using high-end cameras are far more loyal to their brand than users using point-and-shoot cameras, with a probability of staying with the same brand of 60% vs 33%, given that a new camera is bought. Fifth, these “expert” users’ brand congruence reaches 66% for high cliqueness friends. All these differences are statistically significant at 1%.
As for the propagation of new models in the friendship graph, we observe the following. First, the growth of connected components of users converted to a particular, new camera model differs distinctly from random growth. Second, the decline of dissemination of a particular model is close to random decline. This illustrates that users influence their friends to change to a particular new model, rather than from a particular old model. Third, having many converted friends increases the probability of the user to convert herself. Here differences between friends from the same or from different countries are more pronounced for point-and-shoot than for digital single-lens reflex users. Fourth, there was again a distinct difference between arbitrary friends and high cliqueness friends in terms of prediction quality for conversion.
Understanding and Improving Computational Science Storage Access through Continuous Characterization
Authors: Carns Philip , Harms Kevin , Allcock William , Bacon Charles , Lang Samuel , Latham Robert , Ross Robert 
Published: October 2011

Computational science applications are driving a demand for increasingly powerful storage systems. While many techniques are available for capturing the I/O behavior of individual application trial runs and specific components of the storage system, continuous characterization of a production system remains a daunting challenge for systems with hundreds of thousands of compute cores and multiple petabytes of storage. As a result, these storage systems are often designed without a clear understanding of the diverse computational science workloads they will support.
In this study, we outline a methodology for scalable, continuous, systemwide I/O characterization that combines storage device instrumentation, static file system analysis, and a new mechanism for capturing detailed application-level behavior. This methodology allows us to identify both system-wide trends and application-specific I/O strategies. We demonstrate the effectiveness of our methodology by performing a multilevel, two-month study of Intrepid, a 557-teraflop IBM Blue Gene/P system. During that time, we captured application-level I/O characterizations from 6,481 unique jobs spanning 38 science and engineering projects. We used the results of our study to tune example applications, highlight trends that impact the design of future storage systems, and identify opportunities for improvement in I/O characterization methodology.
SYK inhibition and response prediction in diffuse large B-cell lymphoma
Authors: Cheng Shuhua , Coffey Greg , Zhang X. Hannah , Shaknovich Rita , Song Zibo , Lu Pin , Pandey Anjali , Melnick Ari M. , Sinha Uma , Wang Y. Lynn 
Published: October 2011

Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, and the role of SYK in its pathogenesis is not completely understood. Using tissue microarray, we demonstrated for the first time that SYK protein is activated in 27 of 61 (44%) primary human DLBCL tissues. Among DLBCL cell lines, 7 were sensitive and 3 were resistant to a highly specific SYK inhibitor, PRT060318. In sensitive DLBCL cells, SYK inhibition blocked the G1-S transition and caused cell-cycle arrest. This effect was reproduced by genetic reduction of SYK using siRNA. A detailed analysis of the BCR signaling pathways revealed that the consequence of SYK inhibition on PLCγ2 and AKT, as opposed to ERK1/2, was responsible for cell-cycle arrest. Genetic knock-down of these key molecules decelerated the proliferation of lymphoma cells. In addition, BCR signaling can be blocked by PRT060318 in primary lymphoma cells. Together, these findings provide insights into cellular pathways required for lymphoma cell growth and support the rationale for considering SYK inhibition as a potentially useful therapy for DLBCL. The results further suggest the possibility of using PLCγ2 and AKT as biomarkers to predict therapeutic response in prospective clinical trials of specific SYK inhibitors.
Improving accuracy of protein-protein interaction prediction by considering the converse problem for sequence representation
Authors: Ren Xianwen , Wang Yong-Cui , Wang Yong , Zhang Xiang-Sun , Deng Nai-Yang 
Published: October 2011

Abstract

Background
With the development of genome-sequencing technologies, protein sequences are readily obtained by translating the measured mRNAs. Therefore predicting protein-protein interactions from the sequences is of great demand. The reason lies in the fact that identifying protein-protein interactions is becoming a bottleneck for eventually understanding the functions of proteins, especially for those organisms barely characterized. Although a few methods have been proposed, the converse problem, if the features used extract sufficient and unbiased information from protein sequences, is almost untouched.

Results
In this study, we interrogate this problem theoretically by an optimization scheme. Motivated by the theoretical investigation, we find novel encoding methods for both protein sequences and protein pairs. Our new methods exploit sufficiently the information of protein sequences and reduce artificial bias and computational cost. Thus, it significantly outperforms the available methods regarding sensitivity, specificity, precision, and recall with cross-validation evaluation and reaches ~80% and ~90% accuracy in Escherichia coli and Saccharomyces cerevisiae respectively. Our findings here hold important implication for other sequence-based prediction tasks because representation of biological sequence is always the first step in computational biology.

Conclusions
By considering the converse problem, we propose new representation methods for both protein sequences and protein pairs. The results show that our method significantly improves the accuracy of protein-protein interaction predictions.
In vitro anti-plasmodial activity of Dicoma anomala subsp. gerrardii (Asteraceae): identification of its main active constituent, structure-activity relationship studies and gene expression profiling
Authors: Becker John VW , van der Merwe Marina M , van Brummelen Anna C , Pillay Pamisha , Crampton Bridget G , Mmutlane Edwin M , Parkinson Chris , van Heerden Fanie R , Crouch Neil R , Smith Peter J , Mancama Dalu T , Maharaj Vinesh J 
Published: October 2011

Abstract

Background
Anti-malarial drug resistance threatens to undermine efforts to eliminate this deadly disease. The resulting omnipresent requirement for drugs with novel modes of action prompted a national consortium initiative to discover new anti-plasmodial agents from South African medicinal plants. One of the plants selected for investigation was Dicoma anomala subsp. gerrardii, based on its ethnomedicinal profile.

Methods
Standard phytochemical analysis techniques, including solvent-solvent extraction, thin-layer- and column chromatography, were used to isolate the main active constituent of Dicoma anomala subsp. gerrardii. The crystallized pure compound was identified using nuclear magnetic resonance spectroscopy, mass spectrometry and X-ray crystallography. The compound was tested in vitro on Plasmodium falciparum cultures using the parasite lactate dehydrogenase (pLDH) assay and was found to have anti-malarial activity. To determine the functional groups responsible for the activity, a small collection of synthetic analogues was generated - the aim being to vary features proposed as likely to be related to the anti-malarial activity and to quantify the effect of the modifications in vitro using the pLDH assay. The effects of the pure compound on the P. falciparum transcriptome were subsequently investigated by treating ring-stage parasites (alongside untreated controls), followed by oligonucleotide microarray- and data analysis.

Results
The main active constituent was identified as dehydrobrachylaenolide, a eudesmanolide-type sesquiterpene lactone. The compound demonstrated an in vitro IC50 of 1.865 μM against a chloroquine-sensitive strain (D10) of P. falciparum. Synthetic analogues of the compound confirmed an absolute requirement that the α-methylene lactone be present in the eudesmanolide before significant anti-malarial activity was observed. This feature is absent in the artemisinins and suggests a different mode of action. Microarray data analysis identified 572 unique genes that were differentially expressed as a result of the treatment and gene ontology analysis identified various biological processes and molecular functions that were significantly affected. Comparison of the dehydrobrachylaenolide treatment transcriptional dataset with a published artesunate (also a sesquiterpene lactone) dataset revealed little overlap. These results strengthen the notion that the isolated compound and the artemisinins have differentiated modes of action.

Conclusions
The novel mode of action of dehydrobrachylaenolide, detected during these studies, will play an ongoing role in advancing anti-plasmodial drug discovery efforts.
Mizoribine provides effective treatment of sequential histological change of arteritis and reduction of inflammatory cytokines and chemokines in an animal model of Kawasaki disease
Authors: Takahashi Kei , Oharaseki Toshiaki , Nagao Tomokazu , Yokouchi Yuki , Yamada Hitomi , Nagi-Miura Noriko , Ohno Naohito , Saji Tsutomu , Okazaki Tomio , Suzuki Kazuo 
Published: October 2011

AbstractBackgroundIntravenous immunoglobulin (IVIg) treatment results in an effective response from patients with acute-phase Kawasaki disease (KD), but 16.5% of them remain nonresponsive to IVIg. To address this therapeutic challenge, we tried a new therapeutic drug, mizoribine (MZR), in a mouse model of KD, which we have established using injections ofCandida albicanswater-soluble fractions (CAWS).MethodsCAWS (4 mg/mouse) were injected intraperitoneally into C57BL/6N mice for 5 consecutive days. MZR or IgG was administered for 5 days. After 4 weeks, the mice were sacrificed and autopsied, the hearts were fixed in 10% neutral formalin, and plasma was taken to measure cytokines and chemokines using the Bio-Plex system.The incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α, TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.ResultsThe incidence of panvasculitis in the coronary arteries and aortic root was 100% in the control group. The incidence of panvasculitis in the MZR group decreased to 50%. Moreover, the scope and severity of the inflammation of those sites were significantly reduced in the MZR group as well as the IgG group. On the other hand, increased cytokines and chemokines, such as IL-1α TNF-α, KC, MIP-1α, GM-CSF, and IL-13, in the nontreatment group were significantly suppressed by treatment with MZR, but the MCP-1 level increased. In addition, IL-1α, TNF-α, IL-10, IL-13, and MIP-1α were suppressed by treatment in the IgG group.ConclusionMZR treatment suppressed not only the incidence, range, and degree of vasculitis, but also inflammatory cytokines and chemokines in the plasma of the KD vasculitis model mice, suggesting that MZR may be useful for treatment of KD.