bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an Instrumented Drill String for Measuring Drilling Forces
Authors: Peterson Jeffrey Shawn , Kim Brian
Published: January 2018

The National Institute for Occupational Safety and Health (NIOSH) Pittsburgh Mining Research Division (PMRD) conducts a wide variety of mining-related health and safety research. As part of this research, PMRD’s Workplace Health Branch maintains a Noise Control Team tasked with developing noise controls to reduce future incidences of noise-induced hearing loss (NIHL) among the nation’s mining workforce. A noise control project that PMRD is currently investigating is the development of noise controls to reduce the noise emissions from jumbo drills. Operators of jumbo drills are frequently overexposed to noise, putting them at risk of NIHL. A key contributor to the noise at the operator location is the noise radiated from the jumbo drill string, or drill rod. Jumbo drilling is rotary-percussive in nature, and the drill string is mechanically excited by the cutting of the media as well as by a percussive hammer. These excitations travel from the bit/rock interface and from the drifter hammer into the drill string, vibrating the structure and causing it to radiate noise. The development of an instrumented drill string will allow NIOSH to quantify the forces within the drill string during drilling, providing critical information for the development of jumbo drill noise controls.
Time-of-flight secondary ion mass spectrometry analyses of vancomycin
Authors: Du Lin , Yang Xiaohui , Li Wenqiang , Li Haoying , Feng Shanbao , Zeng Rong , Yu Bin , Xiao Liangxing , Liu Yu , Tu Mei , Nie Heng-Yong
Published: January 2018

As an antibiotic that prevents and treats infections caused by Gram-positive bacteria such as Staphylococcus aureus, vancomycin incorporated in a biodegradable polymer poly(lactide-co-glycolide) provides opportunities to construct controlled-release drug delivery systems. Developments associated with this promising system have been largely concentrated on areas of drug delivery kinetics and biodegradability. In order to provide surface analytical approaches to this important system, the authors demonstrate applicability of time-of-flight secondary ion mass spectrometry (TOF-SIMS) in three-dimensional molecular imaging for a model system consisting of alternating layers of ploy(lactide-co-glycolide) and vancomycin. TOF-SIMS imaging clarified that the two chemicals can undergo phase separation when dimethyl sulfoxide is used as the solvent. The authors identified two diagnostic ions that are abundant and structural moieties of vancomycin. The results on TOF-SIMS imaging and depth profiling vancomycin provide useful information for further applications of TOF-SIMS in the development of antibiotic drug delivery systems involving the use of vancomycin.
An equivalent fluid model based finite-difference time-domain algorithm for sound propagation in porous material with rigid frame
Authors: Zhao Jing , Bao Ming , Wang Xiaolin , Lee Hyojin , Sakamoto Shinichi
Published: January 2018

An equivalent fluid model based finite-difference time-domain algorithm is proposed to simulate the frequency characteristic of porous material with rigid frame. The rigid-frame porous material is replaced by an equivalent fluid characterized by the effective density and the effective bulk modulus, which reflect the viscous effects and thermal effects in the porous material, respectively. The effective density and the effective bulk modulus are frequency-dependent complex values, which are designed in the form of infinite impulse response filters in the frequency domain. The Z transform theory is used to discretize the frequency-domain wave equations. The accuracy of the proposed algorithm is preliminarily validated by good agreement between the calculated and measured normal-incidence sound absorption coefficients of two samples composed of different multiple-layered materials in a wide frequency range.
Factoring in new gene therapy treatments for hemophilia A
Authors: Byrne Leah C.
Published: January 2018

Delivery of a modified factor VIII gene leads to dramatic improvement of severe hemophilia A in human trials.
Zika–associated microcephaly: Reduce the stress and race for the treatment
Authors: Novarino Gaia
Published: January 2018

Inhibition of the endoplasmic reticulum stress pathway may hold the key to Zika virus–associated microcephaly treatment.
In Vitro
Susceptibility of Neisseria gonorrhoeae Strains to Mupirocin, an Antibiotic Reformulated for Parenteral Administration in Nanoliposomes
Authors: Cern Ahuva , Connolly Kristie L. , Jerse Ann E. , Barenholz Yechezkel
Published: January 2018

Neisseria gonorrhoeae
is an urgent antibiotic-resistant threat. This study determined the MICs of mupirocin to be 0.0039 to 0.0625 μg/ml for 94
N. gonorrhoeae
strains. Cross-resistance with other antibiotics was not detected. Mupirocin, which is currently limited to topical administration, demonstrated activity by injection when delivered in nanoliposomes. The nanoliposomal formulation of mupirocin is a potential treatment for drug-resistant
N. gonorrhoeae
.
Complete Genome Sequence of a Bacteriophage, pVco-5, That Infects
Vibrio coralliilyticus
, Which Causes Bacillary Necrosis in Pacific Oyster (
Crassostrea gigas
) Larvae
Authors: Kim Hyoun Joong , Jun Jin Woo , Giri Sib Sankar , Chi Cheng , Yun Saekil , Kim Sang Guen , Kim Sang Wha , Kang Jeong Woo , Han Se Jin , Park Se Chang
Published: January 2018

We report here the complete genome sequence of the
Vibrio coralliilyticus
-specific phage pVco-5, a double-stranded DNA virus isolated from an oyster hatchery tank.
Vibrio coralliilyticus
causes bacillary necrosis in marine bivalve larvae; hence, phage pVco-5 could be used to prevent
V. coralliilyticus
infections in these larvae.
Eight Genome Sequences of Cluster BE1 Phages That Infect
Streptomyces
Species
Authors: Hughes Lee E. , Shaffer Christopher D. , Ware Vassie C. , Aguayo Issac , Aziz Rahat M. , Bhuiyan Swapan , Bindert Isaac S. , Calovich-Benne Canyon K. , Chapman Jordyn , Donegan-Quick Richard , Farooq Amal , Garcia Cynthia , Graham Lee H. , Green Baylee Y. , Kenna Margaret A. , Kneeream Emily R. , Laing Christian E. , Mageeney Catherine M. , Meridew Sandra N. , Mikolon Abigail R. , Morgan Ryann E. , Nayek Subhayu , Olugbade Idowu D. , Pike Kim C. , Schlegel Lauren E. , Shishido Taylor C. , Suresh Tara , Suri Nikita , Weston Hafer Kathleen , Garlena Rebecca A. , Russell Daniel A. , Cresawn Steven G. , Pope Welkin H. , Jacobs-Sera Deborah , Hatfull Graham F.
Published: January 2018

Cluster BE1
Streptomyces
bacteriophages belong to the
Siphoviridae
, with genome sizes over 130 kbp, and they contain direct terminal repeats of approximately 11 kbp. Eight newly isolated closely related cluster BE1 phages contain 43 to 48 tRNAs, one transfer-messenger RNA (tmRNA), and 216 to 236 predicted open reading frames (ORFs), but few of their genes are shared with other phages, including those infecting
Streptomyces
species.
Complete Genome Sequence of the
Escherichia coli
Phage Ayreon
Authors: Vlot Marnix , Nobrega Franklin L. , Wong Che F. A. , Liu Yue , Brouns Stan J. J.
Published: January 2018

We report the whole-genome sequence of a new
Escherichia coli
temperate phage, Ayreon, comprising a linear double-stranded DNA (dsDNA) genome of 44,708 bp.
Complete Genome Sequence of
Chryseobacterium camelliae
Dolsongi-HT1, a Green Tea Isolate with Keratinolytic Activity
Authors: Kim Eun-Mi , Hwang Kyeong Hwan , Park Jun-Seong
Published: January 2018

The complete genome sequence of
Chryseobacterium camelliae
Dolsongi-HT1 is reported here.
C. camelliae
Dolsongi-HT1, having keratinolytic activity, was isolated from green tea leaves in the Dolsongi tea garden in Jeju, South Korea. The strain Dolsongi-HT1 has 28 candidate protease genes, which may be utilized in further studies and industrial applications of keratinase.
Coassociation between Group B Streptococcus and Candida albicans Promotes Interactions with Vaginal Epithelium
Authors: Pidwill Grace R. , Rego Sara , Jenkinson Howard F. , Lamont Richard J. , Nobbs Angela H.
Published: January 2018

Group BStreptococcus(GBS) is a leading cause of neonatal sepsis, pneumonia, and meningitis worldwide. In the majority of cases, GBS is transmitted vertically from mother to neonate, making maternal vaginal colonization a key risk factor for neonatal disease. The fungusCandida albicansis an opportunistic pathogen of the female genitourinary tract and the causative agent of vaginal thrush. Carriage ofC. albicanshas been shown to be an independent risk factor for vaginal colonization by GBS. However, the nature of interactions between these two microbes is poorly understood. This study provides evidence of a reciprocal, synergistic interplay between GBS andC. albicansthat may serve to promote their cocolonization of the vaginal mucosa. GBS strains NEM316 (serotype III) and 515 (serotype Ia) are shown to physically interact withC. albicans, with the bacteria exhibiting tropism for candidal hyphal filaments. This interaction enhances association levels of both microbes with the vaginal epithelial cell line VK2/E6E7. The ability of GBS to coassociate withC. albicansis dependent upon expression of the hypha-specific adhesin Als3. In turn, expression of GBS antigen I/II family adhesins (Bsp polypeptides) facilitates this coassociation and confers upon surrogateLactococcus lactisthe capacity to exhibit enhanced interactions withC. albicanson vaginal epithelium. As genitourinary tract colonization is an essential first step in the pathogenesis of GBS andC. albicans, the coassociation mechanism reported here may have important implications for the risk of disease involving both of these pathogens.
Early back-calculated size-at-age of Atlantic yellow eels sampled along ecological gradients in the Gironde and St. Lawrence hydrographical systems
Authors: Patey Géraldine , Couillard Catherine M. , Drouineau Hilaire , Verreault Guy , Pierron Fabien , Lambert Patrick , Baudrimont Magalie , Couture Patrice
Published: January 2018

An international sampling program investigating the causes of the decline of American eels (Anguilla rostrata) and European eels (Anguilla anguilla) in the St. Lawrence (Canada) and Gironde (France) rivers systems provided the opportunity to compare early growth of eels of each species among habitats using back-calculated size-at-age from 1 to 5 years old. Our study supports previous studies showing that the early back-calculated lengths of A. anguilla were higher in downstream and more saline Gironde system habitats than in the upstream fluvial section and provides a new indication that length at 1 year old is twice higher than that reported 10 years earlier. However, our data contradict the current paradigm for A. rostrata by providing evidence that early size-at-age of eels from the upstream St. Lawrence system, most distant from the spawning area, exceeds those of eels sampled downstream, at less distant sites in the estuarine section. Overall, these observations are consistent with the hypothesis that the observed spatial variations in early growth rate of yellow eels sampled in the St. Lawrence and Gironde systems are the consequence of processes occurring in the first year of age, such as genetic selection and (or) genetically dependent habitat choice.
Nebivolol attenuates oxidative stress and inflammation in a guinea pig model of ovalbumin-induced asthma: a possible mechanism for its favorable respiratory effects
Authors: Abuelezz Sally A.
Published: January 2018

An experimental model of ovalbumin (OVA) induced asthma was used to assess the effects of nebivolol, the third-generation selective β1-adrenergic receptor blocker, on airway reactivity, lung inflammation, and oxidative stress markers. The asthma induction protocol was done by OVA sensitization and challenge. Guinea pigs were classified into control, asthmatic, or asthmatic receiving nebivolol either 7.5 or 15 mg·kg–1·day–1orally. At the end of the study respiratory, the anti-inflammatory and antioxidative effects of nebivolol were assessed. The asthmatic group exhibited a significant increase in early and late airway resistance, airway hyperreactivity to histamine, total and absolute leucocytic count, tumor necrosis factor-α, and interleukin-6 in bronchoalveolar lavage fluid and lung lipid peroxidation and a significant decrease in superoxide dismutase and glutathione compared to the control group. Additionally, there was a significant decrease in lung endothelial nitric oxide synthase (eNOS) and a significant increase in inducible nitric oxide synthase (iNOS) mRNA expression compared to the control group. The high dose of nebivolol counteracted the increased airway resistance induced by OVA, whereas it had no effect on airway hyperresponsiveness. Moreover, nebivolol exhibited significant anti-inflammatory and antioxidant effects and restored the altered levels of eNOS and iNOS compared to the asthmatic group. Collectively, these results suggest a beneficial effect of nebivolol in asthma.
A Fully Automatic h-Adaptive Analysis Procedure Using the Edge-Based Smoothed Point Interpolation Method
Authors: Tang Qian , Wei Kexiang , Zhang Guiyong , Sun Xiaogang
Published: January 2018

Within the framework of edge-based smoothed point interpolation method (ES-PIM), a fully automatic adaptive procedure has been proposed by introducing a novel local critical value definition. Owing to the softened stiffness, ES-PIM can generally provide much better results than the traditional finite element method using the simplest linear triangle elements. By comparing with most adaptive models which need to set a refinement rate manually, a novel local critical value considering the area-dependent average magnitude of error indicator for all the cells has been introduced in this work, which leads to an adaptive ES-PIM model without manual operation during the adaptive process. Numerical results have shown that the present adaptive model conducts the adaptive process dynamically, adds the new nodes properly and provides more accurate results with less field nodes than both the model with uniform refinement and the adaptive model using predefined refinement rate. Also considering linear triangular background elements used, the present method is supposed to have much potential for solving complicated engineering problems.
National Culture and Governance on Bondholder Wealth: Evidence from Joint Ventures and Strategic Alliances around the World
Authors: Chen Jun , King Tao-Hsien Dolly , Li Xinxin
Published: January 2018

This paper examines bondholder wealth effects in global business collaborations with the form of cross-border joint ventures (JVs) and strategic alliances (SAs). Based on a sample of 1,898 event-firms from 2009 to 2015, we find significant and positive abnormal returns for bondholders. On average, bondholder value increases 14.4 basis points in a 3-month observation window. We find that country-level governance and national culture are dominant drivers of bondholder wealth effects. More specifically, bondholders benefit more from JVs and SAs if they are from countries with poorer institutional governance or greater regulatory governance in creditor protection (higher creditor rights and lower shareholder rights). In addition, bondholders gain more when they are from countries characterized with greater individualism, less power distance, a higher level of trust, or larger culture distance. Robustness tests and subsample analyses confirm the main findings. We find a positive impact of JVs and SAs on stockholder wealth, but little evidence for wealth transfer between stockholders and bondholders.
Enhancing Reputation via Price Discounts in E-Commerce Systems
Authors: Xie Hong , Ma Richard T. B. , Lui John C. S.
Published: January 2018

Reputation systems have become an indispensable component of modern E-commerce systems, as they help buyers make informed decisions in choosing trustworthy sellers. To attract buyers and increase the transaction volume, sellers need to earn reasonably high reputation scores. This process usually takes a substantial amount of time. To accelerate this process, sellers can provide price discounts to attract users, but the underlying difficulty is that sellers have no prior knowledge on buyers’ preferences over price discounts. In this article, we develop an online algorithm to infer the optimal discount rate from data. We first formulate an optimization framework to select the optimal discount rate given buyers’ discount preferences, which is a tradeoff between the
short-term profit
and the
ramp-up time
(for reputation). We then derive the closed-form optimal discount rate, which gives us key insights in applying a
stochastic bandits framework
to infer the optimal discount rate from the transaction data with regret upper bounds. We show that the computational complexity of evaluating the performance metrics is infeasibly high, and therefore, we develop efficient randomized algorithms with guaranteed performance to approximate them. Finally, we conduct experiments on a dataset crawled from eBay. Experimental results show that our framework can trade 60% of the short-term profit for reducing the ramp-up time by 40%. This reduction in the ramp-up time can increase the long-term profit of a seller by at least 20%.
SRC: geospatial visual analytics belongs to database systems
Authors: Yu Jia
Published: January 2018

GeoVisual analytics,
abbr. GeoViz
, is the science of analytical reasoning assisted by GeoVisual map interfaces. For example, a GeoViz heat map of the New York City taxi trips tells the taxi company where the hot pick-up and drop-off locations are. GeoViz involves the following two memory and compute intensive phases:
Phase I: Spatial Data Preparation:
In this phase, the system first loads the designated spatial data from the database (e.g., Shape files, PostGIS, HDFS). Based on the application, the system may then need to perform data processing operations (e.g., spatial range query, spatial join query) on the loaded spatial data to return the set of spatial objects to be visualized.
Phase II: Map Visualization:
In this phase, the system applies the map visualization effect, e.g., Heatmap, on the spatial objects produced in the Phase I. The system first pixelizes the spatial objects, then aggregates overlapped pixels, and finally renders an image for each geospatial map tile.
SRC
Authors: Lian Jing
Published: January 2018

Customized bus (CB) services that operate between residential areas and work places during rush hours have surfaced in many cities to deal with traffic congestion problem. One major challenge of CB services is to design service areas based on user demands. To solve this problem, we extract commute patterns from large-scale taxi GPS data for CB service area design. We present a novel clustering algorithm that embeds origin and destination data to a low dimensional feature space, such that the resulting patterns satisfy both the needs of commuters and operators. The algorithm has been tested on both synthesized and real-world data.
Overview of the ASSETS 2017 conference
Authors: Hurst Amy , Findlater Leah , Morris Meredith Ringel
Published: January 2018

This year was the 19th edition of the ACM SIGACCESS International Conference on Computers and Accessibility (ASSETS 2017), which took place in October in Baltimore, Maryland, USA. The ASSETS conference is the premier computing research conference exploring the design, evaluation, and use of computing and information technologies to benefit people with disabilities and older adults. We set a new attendance this year with 200 participants from across the globe. In addition to a rich technical program, an increase in industrial sponsorship allowed the conference to support several receptions, including an event at the National Federation of the Blind on Halloween evening.

SIGACCESS made several awards during this year's conference. The SIGACCESS ASSETS Paper Impact Award was awarded to Keith Edwards, Elizabeth Mynatt and Kathryn Stockton for their 1994 paper "Providing access to graphical user interfaces---not graphical screens". This paper is one of the first to raise and tackle the challenge of providing screen reader capabilities in graphical user interfaces. It proposes that translation of the GUI should be done at a semantic, rather than syntactic level. The 2017 Best Paper Award went to "Evaluating the Usability of Automatically Generated Captions for People who are Deaf or Hard of Hearing" by Sushant Kafle and Matt Huenerfauth. The 2017 Best Student Paper Award went to "Technology-Mediated Sight: A Case Study of Early Adopters of a Low Vision Assistive Technology" by Annuska Zolyomi, Anushree Shukla, and Jaime Snyder. We thank Clayton Lewis from University of Colorado Boulder for Chairing the SIGACCESS Awards Committee and Anne Marie Piper from Northwestern University for chairing the 2017 ASSETS Best Papers Committee.
How do ideas flow around SIGMM conferences?
Authors: Xie Lexing
Published: January 2018

The ACM Multimedia conference just celebrated its quarter century in October 2017. This is a great opportunity to reflect on the intellectual influence of the conference, and the SIGMM community in general.

The progress on big scholarly data allows us to make this task analytical. I download a data dump from Microsoft Academic Graph (MAG) in February 2016. I find all papers from ACM Multimedia (MM), the SIGMM flagship conference - there are 4,346 publication entries from 1993 to 2015. I then search the entire MAG for: (1) any paper that appears in the reference list of these MM papers - 35,829 entries across 1,560 publication venues (including both journals and conferences), with an average of 8.24 per paper; (2) any paper that cites any of these MM papers - 46826 citations from 1694 publication venues, with an average of 10.77 citations per paper.

This data allows us to profile the incoming (references) and outgoing (citations) influence in the community in detail.
Acute downregulation of miR-199a attenuates sepsis-induced acute lung injury by targeting SIRT1
Authors: Liu Yang , Guan Hao , Zhang Ju-Lei , Zheng Zhao , Wang Hong-Tao , Tao Ke , Han Shi-Chao , Su Lin-Lin , Hu Dahai
Published: January 2018

MicroRNA-199a (miR-199a) is a novel gene regulator with an important role in inflammation and lung injury. However, its role in the pathogenesis of sepsis-induced acute respiratory distress syndrome (ARDS) is currently unknown. Our study explored the role of miR-199a in sepsis-induced ARDS and its mechanism of action. First, we found that LPS could upregulate miR-199a in alveolar macrophages. Downregulation of miR-199a inhibited the upregulation of inflammatory cytokines in alveolar macrophages and induced the remission of histopathologic changes, the reduction of proinflammatory cytokines, and the upregulation of apoptosis protein expression in an ARDS lung, showing a protective role for miR-199a. We further identified sirtuin 1 (SIRT1) as a direct target of miR-199a in alveolar macrophages, and the expression of SIRT1 was negatively correlated with the level of miR-199a. The protective role of miR-199a downregulation in LPS-stimulated alveolar macrophages and sepsis-induced ARDS could be attenuated by SIRT1 inhibitor. Taken together, these results indicate that downregulation of miR-199a might protect lung tissue against sepsis-induced ARDS by upregulation of SIRT1 through the suppression of excessive inflammatory responses and the inhibition of cellular apoptosis in lung tissue, suggesting its potential therapeutic effects on sepsis-induced ARDS.
Array profiling reveals contribution of Cthrc1 to growth of the denervated rat urinary bladder
Authors: Zhu Baoyi , Ekman Mari , Svensson Daniel , Lindvall Jessica M. , Nilsson Bengt-Olof , Uvelius Bengt , Swärd Karl
Published: January 2018

Bladder denervation and bladder outlet obstruction are urological conditions that cause bladder growth. Transcriptomic surveys in outlet obstruction have identified differentially expressed genes, but similar studies following denervation have not been done. This was addressed using a rat model in which the pelvic ganglia were cryo-ablated followed by bladder microarray analyses. At 10 days following denervation, bladder weight had increased 5.6-fold, and 2,890 mRNAs and 135 micro-RNAs (miRNAs) were differentially expressed. Comparison with array data from obstructed bladders demonstrated overlap between the conditions, and 10% of mRNAs changed significantly and in the same direction. Many mRNAs, including collagen triple helix repeat containing 1 ( Cthrc1), Prc1, Plod2, and Dkk3, and miRNAs, such as miR-212 and miR-29, resided in the shared signature. Discordantly regulated transcripts in the two models were rare, making up for <0.07% of all changes, and the gene products in this category localized to the urothelium of normal bladders. These transcripts may potentially be used to diagnose sensory denervation. Western blotting demonstrated directionally consistent changes at the protein level, with increases of, e.g., Cthrc1, Prc1, Plod2, and Dkk3. We chose Cthrc1 for further studies and found that Cthrc1 was induced in the smooth muscle cell (SMC) layer following denervation. TGF-β1 stimulation and miR-30d-5p inhibition increased Cthrc1 in bladder SMCs, and knockdown and overexpression of Cthrc1 reduced and increased SMC proliferation. This work defines common and distinguishing features of bladder denervation and obstruction and suggests a role for Cthrc1 in bladder growth following denervation.
MiR-200a negatively regulates TGF-β1-induced epithelial-mesenchymal transition of peritoneal mesothelial cells by targeting ZEB1/2 expression
Authors: Guo Runsheng , Hao Guojun , Bao Yi , Xiao Jun , Zhan Xiaojiang , Shi Xintian , Luo Laimin , Zhou Jing , Chen Qinkai , Wei Xin
Published: January 2018

Although epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells was recognized as the key process of peritoneal fibrosis, which is a major cause of peritoneal failure related to peritoneal dialysis (PD), mechanisms underlying these processes remain largely unknown. In this study, we found that miR-200a was significantly downregulated in peritoneal tissues with fibrosis in a rat model of PD. In vitro, transforming growth factor (TGF)-β1-induced EMT, identified by de novo expression of α-smooth muscle actin and a loss of E-cadherin in human peritoneal mesothelial cells (HPMCs), was associated with downregulation of miR-200a but upregulation of zinc finger E-box-binding homeobox 1/2 (ZEB1/2), suggesting a close link between miR-200a and ZEB1/2 in TGF-β1-induced EMT. It was further demonstrated that miR-200a was able to bind to the 3′UTR of ZEB1/2, and overexpression of miR-200a blocked TGF-β1-induced upregulation of ZEB1/2 and, therefore, inhibited EMT and collagen expression. In contrast, overexpression ZEB1/2 blocked miR-200a inhibition of EMT and collagen expression in HMPCs. In conclusion, miR-200a could negatively regulate TGF-β1-induced EMT by targeting ZEB1/2 in peritoneal mesothelial cells. Blockade of EMT in HPMCS indicates the therapeutic potential of miR-200a as a treatment for peritoneal fibrosis associated with PD.
A computational model for how the fast afterhyperpolarization paradoxically increases gain in regularly firing neurons
Authors: Jaffe David B. , Brenner Robert
Published: January 2018

The gain of a neuron, the number and frequency of action potentials triggered in response to a given amount of depolarizing injection, is an important behavior underlying a neuron’s function. Variations in action potential waveform can influence neuronal discharges by the differential activation of voltage- and ion-gated channels long after the end of a spike. One component of the action potential waveform, the afterhyperpolarization (AHP), is generally considered an inhibitory mechanism for limiting firing rates. In dentate gyrus granule cells (DGCs) expressing fast-gated BK channels, large fast AHPs (fAHP) are paradoxically associated with increased gain. In this article, we describe a mechanism for this behavior using a computational model. Hyperpolarization provided by the fAHP enhances activation of a dendritic inward current (a T-type Ca2+channel is suggested) that, in turn, boosts rebound depolarization at the soma. The model suggests that the fAHP may both reduce Ca2+channel inactivation and, counterintuitively, enhance its activation. The magnitude of the rebound depolarization, in turn, determines the activation of a subsequent, slower inward current (a persistent Na+current is suggested) limiting the interspike interval. Simulations also show that the effect of AHP on gain is also effective for physiologically relevant stimulation; varying AHP amplitude affects interspike interval across a range of “noisy” stimulus frequency and amplitudes. The mechanism proposed suggests that small fAHPs in DGCs may contribute to their limited excitability.

NEW & NOTEWORTHY The afterhyperpolarization (AHP) is canonically viewed as a major factor underlying the refractory period, serving to limit neuronal firing rate. We recently reported that enhancing the amplitude of the fast AHP (fAHP) in a relatively slowly firing neuron (vs. fast spiking neurons) expressing fast-gated BK channels augments neuronal excitability. In this computational study, we present a novel, quantitative hypothesis for how varying the amplitude of the fAHP can, paradoxically, influence a subsequent spike tens of milliseconds later.
Association between HLA-B Alleles and Carbamazepine-Induced Maculopapular Exanthema and Severe Cutaneous Reactions in Thai Patients
Authors: Sukasem Chonlaphat , Chaichan Chonlawat , Nakkrut Thapanat , Satapornpong Patompong , Jaruthamsophon Kanoot , Jantararoungtong Thawinee , Koomdee Napatrupron , Sririttha Suthida , Medhasi Sadeep , Oo-Puthinan Sarawut , Rerkpattanapipat Ticha , Klaewsongkram Jettanong , Rerknimitr Pawinee , Tuchinda Papapit , Chularojanamontri Leena , Tovanabutra Napatra , Puangpetch Apichaya , Aekplakorn Wichai
Published: January 2018

The HLA-B∗15:02 allele has been reported to have a strong association with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Thai patients. The HLA-B alleles associated with carbamazepine-induced maculopapular exanthema (MPE) and the drug reaction with eosinophilia and systemic symptoms (DRESS) among the Thai population have never been reported. The aim of the present study was to carry out an analysis of the involvement of HLA-B alleles in carbamazepine-induced cutaneous adverse drug reactions (cADRs) in the Thai population. A case-control study was performed by genotyping the HLA-B alleles of Thai carbamazepine-induced hypersensitivity reaction patients (17 MPE, 16 SJS/TEN, and 5 DRESS) and 271 carbamazepine-tolerant controls. We also recruited 470 healthy Thai candidate subjects who had not taken carbamazepine. HLA-B∗15:02 showed a significant association with carbamazepine-induced MPE (P=0.0022, odds ratio (OR) (95% confidence interval [CI]) = 7.27 (2.04–25.97)) and carbamazepine-induced SJS/TEN (P=4.46×10−13; OR (95% CI) = 70.91(19.67–255.65)) when compared with carbamazepine-tolerant controls. Carbamazepine-induced SJS/TEN also showed an association with HLA-B∗15:21 allele (P=0.013; OR (95% CI) = 9.54 (1.61–56.57)) when compared with carbamazepine-tolerant controls. HLA-B∗58:01 allele was significantly related to carbamazepine-induced MPE (P=0.007; OR (95% CI) = 4.73 (1.53–14.66)) and DRESS (P=0.0315; OR (95% CI) = 7.55 (1.20–47.58)) when compared with carbamazepine-tolerant controls. These alleles may serve as markers to predict carbamazepine-induced cADRs in the Thai population.
FPGA Implementation of Reconfigurable Finite State Machine with Input Multiplexing Architecture Using Hungarian Method
Authors: Das Nitish , Priya P. Aruna
Published: January 2018

The mathematical model for designing a complex digital system is a finite state machine (FSM). Applications such as digital signal processing (DSP) and built-in self-test (BIST) require specific operations to be performed only in the particular instances. Hence, the optimal synthesis of such systems requires a reconfigurable FSM. The objective of this paper is to create a framework for a reconfigurable FSM with input multiplexing and state-based input selection (Reconfigurable FSMIM-S) architecture. The Reconfigurable FSMIM-S architecture is constructed by combining the conventional FSMIM-S architecture and an optimized multiplexer bank (which defines the mode of operation). For this, the descriptions of a set of FSMs are taken for a particular application. The problem of obtaining the required optimized multiplexer bank is transformed into a weighted bipartite graph matching problem where the objective is to iteratively match the description of FSMs in the set with minimal cost. As a solution, an iterative greedy heuristic based Hungarian algorithm is proposed. The experimental results from MCNC FSM benchmarks demonstrate a significant speed improvement by 30.43% as compared with variation-based reconfigurable multiplexer bank (VRMUX) and by 9.14% in comparison with combination-based reconfigurable multiplexer bank (CRMUX) during field programmable gate array (FPGA) implementation.
Mining Outlier Data in Mobile Internet‐Based Large Real‐Time Databases
Authors: Liu Xin , Zhou Yanju , Chen Xiaohong
Published: January 2018

Mining outlier data guarantees access security and data scheduling of parallel databases and maintains high‐performance operation of real‐time databases. Traditional mining methods generate abundant interference data with reduced accuracy, efficiency, and stability, causing severe deficiencies. This paper proposes a new mining outlier data method, which is used to analyze real‐time data features, obtain magnitude spectra models of outlier data, establish a decisional‐tree information chain transmission model for outlier data in mobile Internet, obtain the information flow of internal outlier data in the information chain of a large real‐time database, and cluster data. Upon local characteristic time scale parameters of information flow, the phase position features of the outlier data before filtering are obtained; the decision‐tree outlier‐classification feature‐filtering algorithm is adopted to acquire signals for analysis and instant amplitude and to achieve the phase‐frequency characteristics of outlier data. Wavelet transform threshold denoising is combined with signal denoising to analyze data offset, to correct formed detection filter model, and to realize outlier data mining. The simulation suggests that the method detects the characteristic outlier data feature response distribution, reduces response time, iteration frequency, and mining error rate, improves mining adaptation and coverage, and shows good mining outcomes.
Antitumor Effects of Blocking Protein Neddylation in T315I-BCR-ABL Leukemia Cells and Leukemia Stem Cells
Authors: Liu Chang , Nie Danian , Li Juan , Du Xin , Lu Yuhong , Li Yangqiu , Zhou Jingfeng , Jin Yanli , Pan Jingxuan
Published: January 2018

Imatinib revolutionized the treatment of chronic myeloid leukemia (CML), but drug resistance and disease recurrence remain a challenge. In this study, we suggest a novel strategy based on blocking protein neddylation to address BCR-ABL point mutations and leukemia stem cells (LSC) that lie at the root of imatinib-resistant recurrences. On the basis of the finding that the NEDD8-activating enzyme subunit NAE1 is overexpressed in CML cells, we hypothesized that the function of certain neddylation-dependent protein substrates might be targeted to therapeutic ends in imatinib-resistant CML cells and LSCs. In support of this hypothesis, we demonstrated that the NAE1 inhibitor MLN4924 induced G2–M-phase arrest and apoptosis in bulk CML cells with wild-type p53, regardless of their T315I mutation status in BCR-ABL. Moreover, MLN4924 inhibited the survival and self-renewal of primary human CML CD34+ cells and LSCs in CML-bearing mice via accumulation of p27kip1 in the nucleus. Notably, p27kip1 silencing attenuated the suppressive effect of MLN4924 on the maintenance of LSCs in CML-bearing mice. Taken together, our findings offer a preclinical proof of concept for targeting protein neddylation as a novel therapeutic strategy to override mutational and LSC-derived imatinib resistance in CML.

Significance: These findings highlight a mediator of protein neddylation, a type of protein turnover mechanism, as a viable therapeutic target against imatinib-resistant forms of chronic myelogenous leukemia. Cancer Res; 78(6); 1522–36. ©2018 AACR.
V600E BRAF versus Non-V600E BRAF Mutated Lung Adenocarcinomas: Cytomorphology, Histology, Coexistence of Other Driver Mutations and Patient Characteristics
Authors: Salimian Kevan J. , Fazeli Roghayeh , Zheng Gang , Ettinger David , Maleki Zahra
Published: January 2018

Objectives: We analyzed the morphologic features and clinical characteristics of lung adenocarcinomas (ACAs) harboring mutated BRAF. Study Design: A review of the histology/cytology of BRAF-mutated lung ACAs was performed at the Johns Hopkins Hospital from January 1, 2013, to January 1, 2015. Patient demographics, clinical history, and ACA morphology were assessed. Results: Thirty-six cases were identified with a median age of 66 years (range 44-87), 58% (21/36) were female, and 94% (34/36) were current or former smokers. In total, 28% (10/36) had a BRAF-V600E mutation. Concurrent mutations were identified in KRAS in 4 cases (11%), PIK3CA in 2 cases (6%), and AKT1 in 2 cases (6%). No cases tested for ALK rearrangement were positive. The tumor grading varied from well to poorly differentiated, and the architecture assumed various patterns, including papillary, micropapillary, solid/cribriform, lepidic, and acinar. Of the cases with immunostains, 90% (18/20) were TTF-1 positive, 88% (14/16) were napsin-A positive, and 100% (8/8) were P63 negative. Conclusion: Mutated-BRAF lung ACA arose on average in the seventh decade of life in patients who were current or former smokers and was infrequently found in combination with other common lung ACA driver mutations. The actionable V600E mutation was present in <30% of cases, more commonly in females. The histologic grade and architecture of these tumors varied significantly.
Clinical Course and Outcome of Childhood Acquired Platelet Dysfunction with Eosinophilia
Authors: Chotsampancharoen Thirachit , Sripornsawan Pornpun , Duangchu Sarapee , McNeil Edward
Published: January 2018

Acquired platelet dysfunction with eosinophilia (APDE) is a syndrome which manifests as a transient state of platelet dysfunction in the presence of eosinophilia. The aim of this work was to study the clinical course and outcomes of children diagnosed with APDE. The hospital records of children with APDE were retrospectively reviewed and a total of 69 children were included. The mean (standard deviation) age at diagnosis was 6.9 (3.1) years. All of the patients presented with ecchymoses on the extremities, body, and face. None had serious bleeding symptoms. Platelet counts were within the normal range but all of the patients had abnormal platelet morphology by light microscopy. Parasitic infestation was found in 38% and most (87%) were treated with antiparasitic drugs. The median time from the onset of symptoms to remission was 2.6 months (95% CI 1.8-3.1). The overall complete remission rates at 3, 6, and 12 months were 61, 90, and 94%, respectively, with a median follow-up time after remission of 14.0 months (interquartile range 6.0-30.8). Neither univariate nor multivariate analysis indicated any statistically significant determinants for remission time. In our study, APDE was transient with spontaneous remission, no serious bleeding manifestations, and had a benign clinical course.
Black Hole Sign Predicts Poor Outcome in Patients with Intracerebral Hemorrhage
Authors: Li Qi , Yang Wen-Song , Chen Sheng-Li , Lv Fu-Rong , Lv Fa-Jin , Hu Xi , Zhu Dan , Cao Du , Wang Xing-Chen , Li Rui , Yuan Liang , Qin Xin-Yue , Xie Peng
Published: January 2018

Background: In spontaneous intracerebral hemorrhage (ICH), black hole sign has been proposed as a promising imaging marker that predicts hematoma expansion in patients with ICH. The aim of our study was to investigate whether admission CT black hole sign predicts hematoma growth in patients with ICH. Methods: From July 2011 till February 2016, patients with spontaneous ICH who underwent baseline CT scan within 6 h of symptoms onset and follow-up CT scan were recruited into the study. The presence of black hole sign on admission non-enhanced CT was independently assessed by 2 readers. The functional outcome was assessed using the modified Rankin Scale (mRS) at 90 days. Univariate and multivariable logistic regression analyses were performed to assess the association between the presence of the black hole sign and functional outcome. Results: A total of 225 patients (67.6% male, mean age 60.3 years) were included in our study. Black hole sign was identified in 32 of 225 (14.2%) patients on admission CT scan. The multivariate logistic regression analysis demonstrated that age, intraventricular hemorrhage, baseline ICH volume, admission Glasgow Coma Scale score, and presence of black hole sign on baseline CT independently predict poor functional outcome at 90 days. There are significantly more patients with a poor functional outcome (defined as mRS ≥4) among patients with black hole sign than those without (84.4 vs. 32.1%, p < 0.001; OR 8.19, p = 0.001). Conclusions: The CT black hole sign independently predicts poor outcome in patients with ICH. Early identification of black hole sign is useful in prognostic stratification and may serve as a potential therapeutic target for anti-expansion clinical trials.
Mortality After Magnetic Resonance Imaging of the Brain in Patients With Cardiovascular Implantable Devices
Authors: Padmanabhan Deepak , Jondal Mary L. , Hodge David O. , Mehta Ramila A. , Acker Nancy G. , Dalzell Connie M. , Kapa Suraj , Asirvatham Samuel J. , Cha Yong-Mei , Felmlee Joel P. , Watson Robert E. , Friedman Paul A.
Published: January 2018

Background:

Use of magnetic resonance imaging (MRI) brain is restricted in patients with cardiovascular implantable electronic devices (CIEDs). We proposed to determine whether mortality difference exists for patients with non–MRI-conditional CIEDs undergoing brain MRI compared with controls.

Methods and Results:

Retrospective analysis of prospectively collected data was performed to compare all-cause mortality in patients with CIEDs undergoing brain MRI (CIED-MRI) with 3 control groups matched for age, sex, imaging year, and type of CIED: (1) no CIED, brain MRI (no–CIED-MRI); (2) CIED, brain computerized tomography (CT) scan (CIED-CT); and (3) no CIED, brain CT (no–CIED-CT). The primary outcome was a significant difference (
P
<0.05) between estimated mortality rates. Secondary outcomes were changes in device function before and after brain MRI. The estimated all-cause mortality at 5 years for the CIED-MRI group [mean age (±SD), 68.2 years (15.3 years); 61.2% men] was not significantly different from patients who underwent CT with or without a device (CIED-CT group: hazard ratio, 0.814; 95% confidence interval, 0.593–1.117;
P
=0.2; no–CIED-CT group: hazard ratio, 1.149; 95% confidence interval, 0.818–1.613;
P
=0.4). There was a significant increase in mortality between CIED-MRI and no–CIED-MRI groups (hazard ratio, 1.463; 95% confidence interval, 1.019–2.099;
P
=0.04).

Conclusions:

Brain MRI in patients with CIEDs does not carry an increased mortality risk compared with brain CT and can be performed with adherence to appropriate procedural protocols.
Transvenous Lead Extraction in Chronic Kidney Disease and Dialysis Patients With Infected Cardiac Devices
Authors: Barakat Amr F. , Wazni Oussama M. , Tarakji Khaldoun G. , Callahan Thomas , Nimri Nayef , Saliba Walid I. , Shah Shailee , Abdur Rehman Karim , Rickard John , Brunner Michael P. , Martin David O. , Kanj Mohamed , Baranowski Bryan , Cantillon Daniel , Niebauer Mark , Dresing Thomas , Lindsay Bruce D. , Wilkoff Bruce L. , Hussein Ayman A.
Published: January 2018

Background:

Cardiac implantable electronic device infections have been on the rise. A high-risk population is that with renal disease, especially dialysis. We aimed to assess procedural profiles and clinical outcomes of transvenous lead extraction for cardiac implantable electronic device infection based on renal disease status.

Methods and Results:

In 1420 consecutive patients undergoing transvenous lead extraction of infected cardiac implantable electronic devices (1996–2012), we assessed procedural profiles and clinical outcomes in 3 groups: normal renal function (group 1, n=1159), renal dysfunction not requiring dialysis (group 2, n=163), and dialysis (group 3, n=98). A total of 3182 infected leads were extracted. Dialysis patients had shorter lead dwell times and were less likely to require transvenous lead extraction tools but as likely to require femoral workstations. There were higher overall rates of procedure-related complications in dialysis patients (12% versus ≈6% in nondialysis) with no difference in the major complication rates (
P
=not significant). Complete procedural success rates were 94%, 96%, and 94% in groups 1, 2, and 3, respectively (
P
=not significant). There were 4 intraprocedural deaths in group 1 versus none in groups 2 and 3. Mortality rates were significantly higher in dialysis patients both at 1 and 6 months (
P
<0.0001 for both). In multivariable analyses, dialysis status was independently associated with increased mortality risk at 1 and 6 months. Other factors associated with mortality were lead material retention, functional (New York Heart Association) class, and occurrence of procedural complications.

Conclusions:

In patients with cardiac implantable electronic device infection, dialysis status did not seem to add complexity to transvenous lead extraction but was independently associated with increased mortality at 1 and 6 months.