bluuebunny/crossref_metadata_2025 huggingface dataset:
Imaging the distribution of transient viscosity after the 2016
M
w
7.1 Kumamoto earthquake
Authors: Moore James D. P. , Yu Hang , Tang Chi-Hsien , Wang Teng , Barbot Sylvain , Peng Dongju , Masuti Sagar , Dauwels Justin , Hsu Ya-Ju , Lambert Valère , Nanjundiah Priyamvada , Wei Shengji , Lindsey Eric , Feng Lujia , Shibazaki Bunichiro
Published: April 2017

Crustal rock strength from outer space

The response of crustal rock to stresses is challenging to estimate yet vital for determining risks from events such as earthquakes. Moore
et al.
take advantage of the recent
M
w
7.1 Kumamoto earthquake in Japan to determine the rheology of crustal rocks in the region. The observed inversion of the crustal strain rates demonstrates that certain areas have stiff rock and others (e.g., under the Aso volcanic complex) have much weaker rock. The results match up with expectations, which means that the method can successfully measure rock properties over a wide range of strength and large spatial and temporal scales.

Science
, this issue p.
163
Synthesis of a carbon nanobelt
Authors: Povie Guillaume , Segawa Yasutomo , Nishihara Taishi , Miyauchi Yuhei , Itami Kenichiro
Published: April 2017

Stitching a belt out of carbon rings

If you had a molecular scalpel, you could slice a carbon nanotube twice against the long axis to excise a loop of fused phenyl rings. Of course, knives don't come that small. Instead, Povie
et al.
succeeded in stitching together such a nanometer-scale belt in bottom-up fashion from molecular components, using consecutive Wittig reactions (see the Perspective by Siegel). The belt of 12 edge-sharing rings could ultimately be a first step toward more precisely controlled bottom-up syntheses of extended nanotubes.

Science
, this issue p.
172
; see also p.
135
Eating ecosystems
Authors: Brashares Justin S. , Gaynor Kaitlyn M.
Published: April 2017

Wildlife harvest and depletion compromise socioecological stability
An HIV Envelope gp120-Fc Fusion Protein Elicits Effector Antibody Responses in Rhesus Macaques
Authors: Shubin Zhanna , Li Weizhong , Poonia Bhawna , Ferrari Guido , LaBranche Celia , Montefiori David , Zhu Xiaoping , Pauza C. David
Published: April 2017

A goal for HIV prevention programs is to develop safe, effective vaccines that elicit durable and broadly protective antibodies. Many vaccine programs focus on the immune responses to critical epitopes in the gp120 portion of HIV envelope glycoprotein (Env) and seek to improve the quality and quantity of antibodies by altering the sequence, conformation, oligomerization, or glycosylation of gp120 to activate appropriate germ line B cells and mimic the subsequent maturation pathways seen in infected individuals. As a complement to these strategies, we developed dimeric fusion protein immunogens consisting of HIV
BaL
gp120 monomer attached to a Gly/Ser linker that is, in turn, fused to one half of the dimeric Fc domain from rhesus macaque IgG1 (Env-rFc). We envisioned that Env-rFc may mimic some aspects of immune complexes by binding Fc gamma receptors (FcγRs) on immune cells to increase the strength, breadth, and durability of Env-specific antibody responses. The Env-rFc retained a capacity to bind both cell surface CD4 and FcγRs. In a rhesus macaque immunization study, Env-rFc elicited higher gp120 binding antibody titers than Env and elicited antibodies that recognize CD4-induced epitopes. Env-rFc also induced antibodies capable of neutralizing tier 1A HIV pseudotyped viruses and mediating antibody-dependent cellular cytotoxicity, outcomes not observed with monomeric gp120 in our study. Serum antibodies produced in Env-rFc-immunized macaques had increased durability compared to that of Env monomer immunization. Our work suggests that adding IgG1 Fc to Env-based immunogens may stimulate increased effector capacity in the immune sera and improve the protective serum antibody response.
Comparison of Whole-Genome Sequencing Methods for Analysis of Three Methicillin-Resistant Staphylococcus aureus Outbreaks
Authors: Cunningham Scott A. , Chia Nicholas , Jeraldo Patricio R. , Quest Daniel J. , Johnson Julie A. , Boxrud Dave J. , Taylor Angela J. , Chen Jun , Jenkins Gregory D. , Drucker Travis M. , Nelson Heidi , Patel Robin
Published: April 2017

Whole-genome sequencing (WGS) can provide excellent resolution in global and local epidemiological investigations of
Staphylococcus aureus
outbreaks. A variety of sequencing approaches and analytical tools have been used; it is not clear which is ideal. We compared two WGS strategies and two analytical approaches to the standard method of SmaI restriction digestion pulsed-field gel electrophoresis (PFGE) for typing
S. aureus
. Forty-two
S. aureus
isolates from three outbreaks and 12 reference isolates were studied. Near-complete genomes, assembled
de novo
with paired-end and long-mate-pair (8 kb) libraries were first assembled and analyzed utilizing an in-house assembly and analytical informatics pipeline. In addition, paired-end data were assembled and analyzed using a commercial software package. Single nucleotide variant (SNP) analysis was performed using the in-house pipeline. Two assembly strategies were used to generate core genome multilocus sequence typing (cgMLST) data. First, the near-complete genome data generated with the in-house pipeline were imported into the commercial software and used to perform cgMLST analysis. Second, the commercial software was used to assemble paired-end data, and resolved assemblies were used to perform cgMLST. Similar isolate clustering was observed using SNP calling and cgMLST, regardless of data assembly strategy. All methods provided more discrimination between outbreaks than did PFGE. Overall, all of the evaluated WGS strategies yielded statistically similar results for
S. aureus
typing.
Comparison of ePlex Respiratory Pathogen Panel with Laboratory-Developed Real-Time PCR Assays for Detection of Respiratory Pathogens
Authors: Nijhuis R. H. T. , Guerendiain D. , Claas E. C. J. , Templeton K. E.
Published: April 2017

Infections of the respiratory tract can be caused by a diversity of pathogens, both viral and bacterial. Rapid microbiological diagnosis ensures appropriate antimicrobial therapy as well as effective implementation of isolation precautions. The ePlex respiratory pathogen panel (RP panel) is a novel molecular biology-based assay, developed by GenMark Diagnostics, Inc. (Carlsbad, CA), to be performed within a single cartridge for the diagnosis of 25 respiratory pathogens (viral and bacterial). The objective of this study was to compare the performance of the RP panel with those of laboratory-developed real-time PCR assays, using a variety of previously collected clinical respiratory specimens. A total of 343 clinical specimens as well as 29 external quality assessment (EQA) specimens and 2 different Middle East respiratory syndrome coronavirus isolates have been assessed in this study. The RP panel showed an agreement of 97.4% with the real-time PCR assay regarding 464 pathogens found in the clinical specimens. All pathogens present in clinical samples and EQA samples with a threshold cycle (

C
T

) value of <30 were detected correctly using the RP panel. The RP panel detected 17 additional pathogens, 7 of which could be confirmed by discrepant testing. In conclusion, this study shows excellent performance of the RP panel in comparison to real-time PCR assays for the detection of respiratory pathogens. The ePlex system provided a large amount of useful diagnostic data within a short time frame, with minimal hands-on time, and can therefore potentially be used for rapid diagnostic sample-to-answer testing, in either a laboratory or a decentralized setting.
Brain-Eating Amoebae: Predilection Sites in the Brain and Disease Outcome
Authors: Ong Timothy Yu Yee , Khan Naveed Ahmed , Siddiqui Ruqaiyyah
Published: April 2017

Acanthamoeba
spp. and
Balamuthia mandrillaris
are causative agents of granulomatous amoebic encephalitis (GAE), while
Naegleria fowleri
causes primary amoebic meningoencephalitis (PAM). PAM is an acute infection that lasts a few days, while GAE is a chronic to subacute infection that can last up to several months. Here, we present a literature review of 86 case reports from 1968 to 2016, in order to explore the affinity of these amoebae for particular sites of the brain, diagnostic modalities, treatment options, and disease outcomes in a comparative manner.
An Immortalized Human Dorsal Root Ganglion Cell Line Provides a Novel Context To Study Herpes Simplex Virus 1 Latency and Reactivation
Authors: Thellman Nikki M. , Botting Carolyn , Madaj Zachary , Triezenberg Steven J.
Published: April 2017

A defining characteristic of alphaherpesviruses is the establishment of lifelong latency in host sensory ganglia with occasional reactivation causing recurrent lytic infections. As an alternative to rodent models, we explored the use of an immortalized cell line derived from human dorsal root ganglia. HD10.6 cells proliferate by virtue of a transduced tetracycline-regulated v-
myc
oncogene. In the presence of doxycycline, HD10.6 cells mature to exhibit neuronal morphology and express sensory neuron-associated markers such as neurotrophin receptors TrkA, TrkB, TrkC, and RET and the sensory neurofilament peripherin. Infection of mature HD10.6 neurons by herpes simplex virus 1 (HSV-1) results in a delayed but productive infection. However, infection at a low multiplicity of infection (MOI) in the presence of acyclovir results in a quiescent infection resembling latency in which viral genomes are retained in a low number of neurons, viral gene expression is minimal, and infectious virus is not released. At least some of the quiescent viral genomes retain the capacity to reactivate, resulting in viral DNA replication and release of infectious virus. Reactivation can be induced by depletion of nerve growth factor; other commonly used reactivation stimuli have no significant effect.

IMPORTANCE
Infections by herpes simplex viruses (HSV) cause painful cold sores or genital lesions in many people; less often, they affect the eye or even the brain. After the initial infection, the virus remains inactive or latent in nerve cells that sense the region where that infection occurred. To learn how virus maintains and reactivates from latency, studies are done in neurons taken from rodents or in whole animals to preserve the full context of infection. However, some cellular mechanisms involved in HSV infection in rodents are different from those in humans. We describe the use of a human cell line that has the properties of a sensory neuron. HSV infection in these cultured cells shows the properties expected for a latent infection, including reactivation to produce newly infectious virus. Thus, we now have a cell culture model for latency that is derived from the normal host for this virus.
Autologous Stem Cell Transplantation Disrupts Adaptive Immune Responses during Rebound Simian/Human Immunodeficiency Virus Viremia
Authors: Reeves Daniel B. , Peterson Christopher W. , Kiem Hans-Peter , Schiffer Joshua T.
Published: April 2017

Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts the plasma viral load set point and the rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe a lower peak viral load but an unchanged viral set point during viral rebound. The addition of an autologous stem cell transplant before cART withdrawal alters viral dynamics: we found a higher rebound set point but similar peak viral loads compared to the primary infection. Mathematical modeling of the data that accounts for fundamental immune parameters achieves excellent fit to heterogeneous viral loads. Analysis of model output suggests that the rapid memory immune response following treatment interruption does not ultimately lead to better viral containment. Transplantation decreases the durability of the adaptive immune response following cART withdrawal and viral rebound. Our model's results highlight the impact of the endogenous adaptive immune response during primary SHIV infection. Moreover, because we capture adaptive immune memory and the impact of transplantation, this model will provide insight into further studies of cure strategies inspired by the Berlin patient.

IMPORTANCE
HIV patients who interrupt combination antiretroviral therapy (cART) eventually experience viral rebound, the return of viral loads to pretreatment levels. However, the “Berlin patient” remained free of HIV rebound over a decade after stopping cART. His cure is attributed to leukemia treatment that included an HIV-resistant stem cell transplant. Inspired by this case, we studied the impact of stem cell transplantation in a macaque simian/HIV (SHIV) system. Using a mechanistic mathematical model, we found that while primary infection generates an adaptive immune memory response, stem cell transplantation disrupts this learned immunity. The results have implications for HIV cure regimens based on stem cell transplantation.
Membrane Penetration by Bacterial Viruses
Authors: Xu Jingwei , Xiang Ye
Published: April 2017

The bacteriophage ϕ29 infects Gram-positive
Bacillus subtilis
with a short noncontractile tail. Recent studies showed that the ϕ29 tail protein gp9 forms a hexameric tube with six long loops of membrane-active peptides blocking in the tube at the distal end of the tail. The long loops exit on genome release and form a membrane pore for passage of the genome. The membrane penetration mechanism of the ϕ29 tail might be common among tailed bacteriophages.
Genome-Wide Screening Uncovers the Significance of N-Sulfation of Heparan Sulfate as a Host Cell Factor for Chikungunya Virus Infection
Authors: Tanaka Atsushi , Tumkosit Uranan , Nakamura Shota , Motooka Daisuke , Kishishita Natsuko , Priengprom Thongkoon , Sa-ngasang Areerat , Kinoshita Taroh , Takeda Naokazu , Maeda Yusuke
Published: April 2017

The molecular mechanisms underlying chikungunya virus (CHIKV) infection are poorly characterized. In this study, we analyzed the host factors involved in CHIKV infection using genome-wide screening. Human haploid HAP1 cells, into which an exon-trapping vector was introduced, were challenged with a vesicular stomatitis virus pseudotype bearing the CHIKV E3 to E1 envelope proteins. Analysis of genes enriched in the cells resistant to the pseudotyped virus infection unveiled a critical role of N-sulfation of heparan sulfate (HS) for the infectivity of the clinically isolated CHIKV Thai#16856 strain to HAP1 cells. Knockout of NDST1 that catalyzes N-sulfation of HS greatly decreased the binding and infectivity of CHIKV Thai#16856 strain but not infectivity of Japanese encephalitis virus (JEV) and yellow fever virus (YFV). While glycosaminoglycans were commonly required for the efficient infectivity of CHIKV, JEV, and YFV, as shown by using
B3GAT3
knockout cells, the tropism for N-sulfate was specific to CHIKV. Expression of chondroitin sulfate (CS) in
NDST1
-knockout HAP1 cells did not restore the binding of CHIKV Thai#16856 strain and the infectivity of its pseudotype but restored the infectivity of authentic CHIKV Thai#16856, suggesting that CS functions at later steps after CHIKV binding. Among the genes enriched in this screening, we found that TM9SF2 is critical for N-sulfation of HS and therefore for CHIKV infection because it is involved in the proper localization and stability of NDST1. Determination of the significance of and the relevant proteins to N-sulfation of HS may contribute to understanding mechanisms of CHIKV propagation, cell tropism, and pathogenesis.

IMPORTANCE
Recent outbreaks of chikungunya fever have increased its clinical importance. Chikungunya virus (CHIKV) utilizes host glycosaminoglycans to bind efficiently to its target cells. However, the substructure in glycosaminoglycans required for CHIKV infection have not been characterized. Here, we unveil that N-sulfate in heparan sulfate is essential for the efficient infection of a clinical CHIKV strain to HAP1 cells and that chondroitin sulfate does not help the CHIKV binding but does play roles at the later steps in HAP1 cells. We show, by comparing previous reports using Chinese hamster ovary cells, along with another observation that enhanced infectivity of CHIKV bearing Arg82 in envelope E2 does not depend on glycosaminoglycans in HAP1 cells, that the infection manner of CHIKV varies among host cells. We also show that TM9SF2 is required for CHIKV infection to HAP1 cells because it is involved in the N-sulfation of heparan sulfate through ensuring NDST1 activity.
Double Plant Homeodomain Fingers 2 (DPF2) Promotes the Immune Escape of Influenza Virus by Suppressing Beta Interferon Production
Authors: Shin Dongjo , Lee Jihye , Park Ji Hoon , Min Ji-Young
Published: April 2017

The high mutation rates of the influenza virus genome facilitate the generation of viral escape mutants, rendering vaccines and drugs against influenza virus-encoded targets potentially ineffective. Therefore, we identified host cell determinants dispensable for the host but crucial for virus replication, with the goal of preventing viral escape and finding effective antivirals. To identify these host factors, we screened 2,732 human genes using RNA interference and focused on one of the identified host factors, the double plant homeodomain fingers 2 (DPF2/REQ) gene, for this study. We found that knockdown of DPF2 in cells infected with influenza virus resulted in decreased expression of viral proteins and RNA. Furthermore, production of progeny virus was reduced by two logs in the multiple-cycle growth kinetics assay. We also found that DPF2 was involved in the replication of seasonal influenza A and B viruses. Because DPF2 plays a crucial role in the noncanonical NF-κB pathway, which negatively regulates type I interferon (IFN) induction, we examined the relationship between DPF2 and IFN responses during viral infection. The results showed that knockdown of DPF2 resulted in increased expression of IFN-β and induced phosphorylation of STAT1 in infected cells. In addition, high levels of several cytokines/chemokines (interleukin-8 [IL-8], IP-10, and IL-6) and antiviral proteins (MxA and ISG56) were produced by DPF2 knockdown cells. In conclusion, we identified a novel host factor, DPF2, that is required for influenza virus to evade the host immune response and that may serve as a potential antiviral target.

IMPORTANCEInfluenza virus is responsible for seasonal epidemics and occasional pandemics and is an ongoing threat to public health worldwide. Influenza virus relies heavily on cellular factors to complete its life cycle. Here we identified a novel host factor, DPF2, which is involved in influenza virus infection. Our results showed that DPF2 plays a crucial role in the replication and propagation of influenza virus. DPF2 functions in the noncanonical NF-κB pathway, which negatively regulates type I IFN induction. Thus, we investigated the relationship between the IFN response and DPF2 in influenza virus infection. Upon influenza virus infection, DPF2 dysregulated IFN-β induction and expression of cytokines/chemokines and antiviral proteins. This study provides evidence that influenza virus utilizes DPF2 to escape host innate immunity.
Characterization of Pre-F-GCN4t, a Modified Human Respiratory Syncytial Virus Fusion Protein Stabilized in a Noncleaved Prefusion Conformation
Authors: Blais Normand , Gagné Martin , Hamuro Yoshitomo , Rheault Patrick , Boyer Martine , Steff Ann-Muriel , Baudoux Guy , Dewar Vincent , Demers Josée , Ruelle Jean-Louis , Martin Denis
Published: April 2017

The human respiratory syncytial virus (hRSV) fusion (F) protein is considered a major target of the neutralizing antibody response to hRSV. This glycoprotein undergoes a major structural shift from the prefusion (pre-F) to the postfusion (post-F) state at the time of virus-host cell membrane fusion. Recent evidences suggest that the pre-F state is a superior target for neutralizing antibodies compared to the post-F state. Therefore, for vaccine purposes, we have designed and characterized a recombinant hRSV F protein, called Pre-F-GCN4t, stabilized in a pre-F conformation. To show that Pre-F-GCN4t does not switch to a post-F conformation, it was compared with a recombinant post-F molecule, called Post-F-XC. Pre-F-GCN4t was glycosylated and trimeric and displayed a conformational stability different from that of Post-F-XC, as shown by chemical denaturation. Electron microscopy analysis suggested that Pre-F-GCN4t adopts a lollipop-like structure. In contrast, Post-F-XC had a typical elongated conical shape. Hydrogen/deuterium exchange mass spectrometry demonstrated that the two molecules had common rigid folding core and dynamic regions and provided structural insight for their biophysical and biochemical properties and reactivity. Pre-F-GCN4t was shown to deplete hRSV-neutralizing antibodies from human serum more efficiently than Post-F-XC. Importantly, Pre-F-GCN4t was also shown to bind D25, a highly potent monoclonal antibody specific for the pre-F conformation. In conclusion, this construct presents several pre-F characteristics, does not switch to the post-F conformation, and presents antigenic features required for a protective neutralizing antibody response. Therefore, Pre-F-GCN4t can be considered a promising candidate vaccine antigen.

IMPORTANCE
Human respiratory syncytial virus (RSV) is a global leading cause of infant mortality and adult morbidity. The development of a safe and efficacious RSV vaccine remains an important goal. The RSV class I fusion (F) glycoprotein is considered one of the most promising vaccine candidates, and recent evidences suggest that the prefusion (pre-F) state is a superior target for neutralizing antibodies. Our study presents the physicochemical characterization of Pre-F-GCN4t, a molecule designed to be stabilized in the pre-F conformation. To confirm its pre-F conformation, Pre-F-GCN4t was analyzed in parallel with Post-F-XC, a molecule in the post-F conformation. Our results show that Pre-F-GCN4t presents characteristics of a stabilized pre-F conformation and support its use as an RSV vaccine antigen. Such an antigen may represent a significant advance in the development of an RSV vaccine.
Discovery of a Novel Antifungal Agent in the Pathogen Box
Authors: Mayer François L. , Kronstad James W.
Published: April 2017

Cryptococcus neoformans
and
Candida albicans
are two major human fungal pathogens and together account for over 1.4 million infections annually, with very high mortality rates. These fungi often infect immunocompromised individuals, such as HIV/AIDS patients. In an effort to identify novel drugs with antifungal activity, we have screened the Pathogen Box for compounds with anticryptococcal and anticandidal activities. This approach led to the discovery of a promising lead compound (MMV688271) with strong antifungal potency under nutrient-limited conditions.
Neonatal airway: challenging endotracheal intubation in infants with tracheal malformations at birth
Authors: Agarwal Arpan , Nakao Masakazu , Rajadurai Victor Samuel , Chandran Suresh
Published: April 2017

Intubating newborn infants can be exacting. We describe two cases of endotracheal intubations in infants born with tracheal malformations. A male infant aged 30 weeks required intubation at birth for respiratory distress. Repeated attempts at intubation failed to achieve an optimal endotracheal tube position as the tube could not advance beyond the vocal cords. Hence ventilation continued with suboptimal air entry in the lungs. Bronchoscopy and CT scan confirmed tracheal stenosis. Slide tracheoplasty was successfully executed on day 78 of life. A female infant aged 33 weeks was intubated at birth for perinatal depression. Attempts at intubation were unsuccessful due to non-visualisation of the laryngeal inlet. Oesophagus was intubated and attempts to inflate showed air entry in the lungs, suggesting a fistulous communication between oesophagus and airway. A contrast oesophagogram showed a fistula connecting oesophagus and carina. With airway patency in question and associated major anomalies, parents were counselled and support was withdrawn.
Hand exercises for patients with rheumatoid arthritis: an extended follow-up of the SARAH randomised controlled trial
Authors: Williamson Esther , McConkey Christopher , Heine Peter , Dosanjh Sukhdeep , Williams Mark , Lamb Sarah E
Published: April 2017

Objectives

The Stretching And strengthening for Rheumatoid Arthritis of the Hand (SARAH) randomised controlled trial evaluated the effectiveness of a hand exercise programme and demonstrated it was clinically effective and cost-effective at 12 months. The aim of this extended follow-up was to evaluate the effects of the SARAH programme beyond 12 months.

Methods

Using postal questionnaires, we collected the Michigan Hand Questionnaire hand function (primary outcome), activities of daily living and work subscales, pain troublesomeness, self-efficacy and health-related quality of life. All participants were asked how often they performed hand exercises for their rheumatoid arthritis. Mean difference in hand function scores were analysed by a linear model, adjusted for baseline score.

Results

Two-thirds (n=328/490, 67%) of the original cohort provided data for the extended follow-up. The mean follow-up time was 26 months (range 19–40 months).

There was no difference in change in hand function scores between the two groups at extended follow-up (mean difference (95% CI) 1.52 (−1.71 to 4.76)). However, exercise group participants were still significantly improved compared with baseline (p=0.0014) unlike the best practice usual care group (p=0.1122). Self-reported performance of hand exercises had reduced substantially.

Conclusions

Participants undertaking the SARAH exercise programme had improved hand function compared with baseline >2 years after randomisation. This was not the case for the control group. However, scores were no longer statistically different between the groups indicating the effect of the programme had diminished over time. This reduction in hand function compared with earlier follow-up points coincided with a reduction in self-reported performance of hand exercises. Further intervention to promote long-term adherence may be warranted.

Trial registration number

ISRCTN89936343; Results.
Hypoxia-inducible factor 1α predicts recurrence in high-grade soft tissue sarcoma of extremities and trunk wall
Authors: Nyström H , Jönsson M , Werner-Hartman L , Nilbert M , Carneiro A
Published: April 2017

Background and aim

Sarcomas are of mesenchymal origin and typically show abundant tumour stroma and presence of necrosis. In search for novel biomarkers for personalised therapy, we determined the prognostic impact of stromal markers, hypoxia and neovascularity in high-grade soft tissue leiomyosarcoma and pleomorphic undifferentiated sarcoma.

Method

We evaluated CD163, colony-stimulating factor (CSF)-1, CD16 and hypoxia-inducible factor 1 (HIF-1)α using immunohistochemical staining and assessed microvessel density using CD31 in 73 high-grade leiomyosarcomas and undifferentiated pleomorphic sarcomas of the extremities and the trunk wall. The results were correlated to metastasis-free and overall survival.

Results

Expression of HIF-1α was associated with the presence of necrosis and independently predicted shorter metastasis-free survival (HR 3.2, CI 1.4 to 7.0, p=0.004), whereas neither expression of the stromal markers CD163, CD16 and CSF-1 nor microvessel density was prognostically relevant in this series.

Conclusions

There is increasing evidence for the prognostic role of hypoxia in high-grade soft tissue sarcoma, and these data suggest that HIF-1α expression represents a candidate prognostic biomarker for clinical application in high-grade leiomyosarcoma and undifferentiated pleomorphic sarcoma.
Republished: Endovascular retrieval of dental needle retained in the internal carotid artery
Authors: Moore Kenneth , Khan Nickalus R , Michael L Madison , Arthur Adam S , Hoit Daniel
Published: April 2017

Intravascular foreign bodies are a known complication of medical and dental procedures. Dental anesthetic needles may be broken off and retained in the oropharynx. These needles have occasionally been reported to migrate through the oral mucosa in to deeper structures. Here we present the case of a 57-year-old man who had a retained dental needle that had migrated into his internal carotid artery. The needle was removed using endovascular techniques. To our knowledge, this is the first report of a retained dental needle being retrieved using this method. We review the literature on intravascular foreign bodies, retained dental needles, and endovascular techniques for retrieval of such foreign bodies.
Can fishways mitigate fragmentation effects on Great Plains fish communities?
Authors: Pennock Casey A. , Bender David , Hofmeier Jordan , Mounts Jessica A. , Waters Ryan , Weaver Vaughn D. , Gido Keith B.
Published: April 2017

Fishways are a common tool for mitigating the effects of habitat fragmentation on fish, but their utility in low-gradient, sand-bed rivers of the Great Plains is not well studied. The Lincoln Street Fishway on the Arkansas River became operational in 2015 and was built specifically to pass small-bodied threatened fishes. We compared current and historical surveys up- and downstream of the barrier to test the effect of the fishway on community structure and conducted tagging experiments to test the ability of fishes to move into and through the fishway. Differences in community structure and species richness between communities up- and downstream of the dam were reduced following construction of the fishway. Surveys within the fishway revealed that 74% of species from the sampled community were using the fishway. Fishes marked with visible implant elastomer downstream of the dam were recaptured in the fishway, qualitatively showing that small-bodied fishes could move into and upstream within the fishway. We further quantified upstream movement for three species of small-bodied minnow tagged with passive integrated transponder tags during manipulations of flows through the fishway. Our results illustrate the potential for fishways to mitigate the effects of habitat fragmentation on fishes in sand-bed rivers.
Do granular systems obey statistical mechanics? A review of recent work assessing the applicability of equilibrium theory to vibrationally excited granular media
Authors: Windows-Yule C. R. K.
Published: April 2017

Driven granular media — assemblies of discrete, macroscopic elements exposed to a source of mechanical energy — represent inherently out-of-equilibrium systems. Although granular media are ubiquitous in both nature and industry, due to their dissipative nature and resultant complex behaviors they remain startlingly poorly understood as compared to classical, thermodynamic systems. Nonetheless, in recent years it has been observed that the behaviors of granular media can, under certain circumstances, closely resemble those of equilibrium systems. One of the most important contemporary questions in the field of granular physics is whether these similarities are merely superficial, or whether the parallels run deep enough that the behaviors of these nonequilibrium systems can in fact be successfully captured using analogs to existing theoretical models developed for classical systems. In this review, we draw together the findings of a variety of recent studies where this question has been addressed, comparing and contrasting the results and conclusions presented. We focus our attention on vibrated and vibrofluidized granular beds, which provide a canonical system representative of various equilibrium and nonequilibrium physical systems, and whose simple dynamics offer a valuable testing ground for exploring the fundamental physics of the granular state.
A non-contact method for determining the junction temperature of GaN-based blue light LED
Authors: Jie Guo , Ma Junshan , Feng Rao
Published: April 2017

A novel method to determine the junction temperature of GaN type blue light LED based on the spectral parameters is proposed. In this method, the relationships among LED junction temperature, centroid wavelength and FWHM are obtained in the lab, and then the junction temperature of operating LED of the same type can be derived from this relationship. A comparative analysis of the junction temperatures which are measured with the centroid wavelength-FWHM method and with the forward voltage method is performed. The standard deviation between these two methods is found to be about 2.3[Formula: see text]C. Therefore, the combination of centroid wavelength and FWHM can be used to determine the junction temperature of GaN-based blue LED.
The study of a novel ultrasonic A-scan signal processing method based on fractal theory
Authors: Zhu Ye , Wei Shi-Cheng , Dong Yu-Cai , Liang Yi , Wang Yu-Jiang
Published: April 2017

Concerning ultrasonic non-destructive testing of ceramic-lined composite steel pipes, a novel bonding flaw locating method based on fractal dimension is proposed. Ultrasonic A-scan method is used on different positions of the composite steel pipe test piece. The fractal dimension of each curve of ultrasonic vibration signal is calculated. The transformation of each fractal dimension is compared and abnormal positions where bonding defects potentially exist are detected. The result indicates that ultrasonic A-scan signal has an excellent fractal conduct characteristic. It is feasible to compare fractal dimension of signal with the normal range and find out abnormal positions, which can provide basis for follow-up inspections.
Peculiarities in the concentration dependence of the superconducting transition temperature in the bipolaron theory of Cooper pairs
Authors: Lakhno Victor
Published: April 2017

It is shown that the bipolaron theory of Cooper pairs suggests that there is a possibility for a superconducting phase to exist at low and high levels of doping and be absent at the intermediate level of doping. The results obtained possibly to imply the universal character of 1/8 anomaly.
Human-derived gut microbiota modulates colonic secretion in mice by regulating 5-HT3 receptor expression via acetate production
Authors: Bhattarai Yogesh , Schmidt Bradley A. , Linden David R. , Larson Eric D. , Grover Madhusudan , Beyder Arthur , Farrugia Gianrico , Kashyap Purna C.
Published: April 2017

Serotonin [5-hydroxytryptamine (5-HT)], an important neurotransmitter and a paracrine messenger in the gastrointestinal tract, regulates intestinal secretion by its action primarily on 5-HT3 and 5-HT4 receptors. Recent studies highlight the role of gut microbiota in 5-HT biosynthesis. In this study, we determine whether human-derived gut microbiota affects host secretory response to 5-HT and 5-HT receptor expression. We used proximal colonic mucosa-submucosa preparation from age-matched Swiss Webster germ-free (GF) and humanized (HM; ex-GF colonized with human gut microbiota) mice. 5-HT evoked a significantly greater increase in short-circuit current (Δ Isc) in GF compared with HM mice. Additionally, 5-HT3 receptor mRNA and protein expression was significantly higher in GF compared with HM mice. Ondansetron, a 5-HT3 receptor antagonist, inhibited 5-HT-evoked Δ Isc in GF mice but not in HM mice. Furthermore, a 5-HT3 receptor-selective agonist, 2-methyl-5-hydroxytryptamine hydrochloride, evoked a significantly higher Δ Isc in GF compared with HM mice. Immunohistochemistry in 5-HT3A-green fluorescent protein mice localized 5-HT3 receptor expression to enterochromaffin cells in addition to nerve fibers. The significant difference in 5-HT-evoked Δ Isc between GF and HM mice persisted in the presence of tetrodotoxin (TTX) but was lost after ondansetron application in the presence of TTX. Application of acetate (10 mM) significantly lowered 5-HT3 receptor mRNA in GF mouse colonoids. We conclude that host secretory response to 5-HT may be modulated by gut microbiota regulation of 5-HT3 receptor expression via acetate production. Epithelial 5-HT3 receptor may function as a mediator of gut microbiota-driven change in intestinal secretion.

NEW & NOTEWORTHY We found that gut microbiota alters serotonin (5-HT)-evoked intestinal secretion in a 5-HT3 receptor-dependent mechanism and gut microbiota metabolite acetate alters 5-HT3 receptor expression in colonoids.

View this article's corresponding video summary at https://www.youtube.com/watch?v=aOMYJMuLTcw&feature=youtu.be .
Glycolytic inhibition by 2-deoxy-d-glucose abolishes both neuronal and network bursts in an in vitro seizure model
Authors: Shao Li-Rong , Stafstrom Carl E.
Published: April 2017

Neuronal activity is energy demanding and coupled to cellular metabolism. In this study, we investigated the effects of glycolytic inhibition with 2-deoxy-d-glucose (2-DG) on basal membrane properties, spontaneous neuronal firing, and epileptiform network bursts in hippocampal slices. The effect of glycolytic inhibition on basal membrane properties was examined in hippocampal CA1 neurons, which are not ordinarily active spontaneously. Intracellular application of 2-DG did not significantly alter the membrane input resistance, action-potential threshold, firing pattern, or input-output relationship of these neurons compared with simultaneously recorded neighboring neurons without intracellular 2-DG. The effect of glycolytic inhibition on neuronal firing was tested in spontaneously active hippocampal neurons (CA3) when synaptic transmission was left intact or blocked with AMPA, NMDA, and GABAA receptor antagonists (DNQX, APV, and bicuculline, respectively). Under both conditions (synaptic activity intact or blocked), bath application of 2-DG (2 mM) blocked spontaneous firing in ~2/3 (67 and 71%, respectively) of CA3 pyramidal neurons. In contrast, neuronal firing of CA3 neurons persisted when 2-DG was applied intracellularly, suggesting that glycolytic inhibition of individual neurons is not sufficient to stop neuronal firing. The effects of 2-DG on epileptiform network bursts in area CA3 were tested in Mg2+-free medium containing 50 µM 4-aminopyridine. Bath application of 2-DG abolished these epileptiform bursts in a dose-dependent and all-or-none manner. Taken together, these data suggest that altered glucose metabolism profoundly affects cellular and network hyperexcitability and that glycolytic inhibition by 2-DG can effectively abrogate epileptiform activity.

NEW & NOTEWORTHY Neuronal activity is highly energy demanding and coupled to cellular metabolism. In this study, we demonstrate that glycolytic inhibition with 2-deoxy-d-glucose (2-DG) effectively suppresses spontaneous neuronal firing and epileptiform bursts in hippocampal slices. These data suggest that an altered metabolic state can profoundly affect cellular and network excitability, and that the glycolytic inhibitor 2-DG may hold promise as a novel treatment of drug-resistant epilepsy.
Microbiotal-Host Interactions and Hypertension
Authors: Galla Sarah , Chakraborty Saroj , Mell Blair , Vijay-Kumar Matam , Joe Bina
Published: April 2017

Hypertension, or elevated blood pressure (BP), has been extensively researched over decades and clearly demonstrated to be caused due to a combination of host genetic and environmental factors. Although much research remains to be conducted to pin-point the precise genetic elements on the host genome that control BP, new lines of evidence are emerging to indicate that, besides the host genome, the genomes of all indigenous commensal micro-organisms, collectively referred to as the microbial metagenome or microbiome, are important, but largely understudied, determinants of BP. Unlike the rigid host genome, the microbiome or the “second genome” can be altered by diet or microbiotal transplantation in the host. This possibility is attractive from the perspective of exploiting the microbiotal composition for clinical management of inherited hypertension. Thus, focusing on the limited current literature supporting a role for the microbiome in BP regulation, this review highlights the need to further explore the role of the co-existence of host and the microbiota as an organized biological unit called the “holobiont” in the context of BP regulation.
Pathophysiology of Aortic Valve Stenosis: Is It Both Fibrocalcific and Sex Specific?
Authors: Sritharen Yoginee , Enriquez-Sarano Maurice , Schaff Hartzell V. , Casaclang-Verzosa Grace , Miller Jordan D.
Published: April 2017

Our understanding of the fundamental biology and identification of efficacious therapeutic targets in aortic valve stenosis has lagged far behind the fields of atherosclerosis and heart failure. In this review, we highlight the most clinically relevant problems facing men and women with fibrocalcific aortic valve stenosis, discuss the fundamental biology underlying valve calcification and fibrosis, and identify key molecular points of intersection with sex hormone signaling.
Feeding Your Baby In Utero: How the Uteroplacental Circulation Impacts Pregnancy
Authors: James Joanna L. , Chamley Lawrence W. , Clark Alys R.
Published: April 2017

The utero-placental circulation links the maternal and fetal circulations during pregnancy, ensuring adequate gas and nutrient exchange, and consequently fetal growth. However, our understanding of this circulatory system remains incomplete. Here, we discuss how the utero-placental circulation is established, how it changes dynamically during pregnancy, and how this may impact on pregnancy success, highlighting how we may address knowledge gaps through advances in imaging and computational modeling approaches.
Oleuropein Protects Cardiomyocyte against Apoptosis via Activating the Reperfusion Injury Salvage Kinase Pathway In Vitro
Authors: Zhao Qiming , Bai Yinliang , Li Caie , Yang Kun , Wei Wansheng , Li Zhenzhen , Pan Li , Li Xiaoming , Zhang Xuanfen
Published: April 2017

Oleuropein, the main glycoside present in olives, has been reported to have cardioprotective effect, but the exact mechanism has not been clearly elucidated. This study attempted to clarify the cardioprotective effect of oleuropein against simulated ischemia/reperfusion‐ (SI/R‐) induced cardiomyocyte injury in vitro and further explore the underlying mechanism. Here we confirmed that oleuropein reduced the cell injury in neonatal rat cardiomyocyte induced by SI/R evidenced by decreasing MTT dye reduction and LDH activity in the culture medium. Meanwhile, the compound also inhibited reactive oxygen species excessive generation and stabilized mitochondrial membrane potential after SI/R. The flow cytometry assessment results indicated the inhibition of cellular apoptosis with oleuropein treatment. Furthermore, western blot analysis showed that oleuropein attenuated the expression of Cyt‐C, c‐caspase‐3, and c‐caspase‐9, increased the Bcl‐2/Bax ratio, and enhanced the phosphorylation of ERK1/2 and Akt after SI/R. However, the phosphorylation enhancement was partially abolished in the presence of LY294002 (PI3K inhibitor) and U0126 (ERK inhibitor). All these findings indicate that oleuropein has the protective potential against SI/R‐induced injury and its protective effect may be partly due to the attenuation of apoptosis via the activation of the PI3K/Akt and ERK1/2 signaling pathways.
Impaired Healing of a Cutaneous Wound in an Inducible Nitric Oxide Synthase-Knockout Mouse
Authors: Kitano Takashi , Yamada Hiroshi , Kida Maki , Okada Yuka , Saika Shizuya , Yoshida Munehito
Published: April 2017

Background. We investigated the effects of loss of inducible nitric oxide synthase (iNOS) on the healing process of cutaneous excisional injury by using iNOS-null (KO) mice. Population of granulation tissue-related cell types, that is, myofibroblasts and macrophages, growth factor expression, and reepithelialization were evaluated.Methods. KO and wild type (WT) mice of C57BL/6 background were used. Under general anesthesia two round full-thickness excision wounds of 5.0 mm in diameter were produced in dorsal skin. After specific intervals of healing, macroscopic observation, histology, immunohistochemistry, and real-time reverse transcription-polymerase chain reaction (RT-PCR) were employed to evaluate the healing process.Results. The loss of iNOS retards granulation tissue formation and reepithelialization in excision wound model in mice. Detailed analyses showed that myofibroblast appearance, macrophage infiltration, and mRNA expression of transforming growth factor b and of collagen 1α2 were all suppressed by lacking iNOS.Conclusions. iNOS is required in the process of cutaneous wound healing. Lacking iNOS retards macrophage invasion and its expression of fibrogenic components that might further impair fibrogenic behaviors of fibroblasts.
Identification of ICS Security Risks toward the Analysis of Packet Interaction Characteristics Using State Sequence Matching Based on SF-FSM
Authors: Xu Jianxin , Feng Dongqin
Published: April 2017

This paper discusses two aspects of major risks related to the cyber security of an industrial control system (ICS), including the exploitation of the vulnerabilities of legitimate communication parties and the features abused by unauthorized parties. We propose a novel framework for exposing the above two types of risks. A state fusion finite state machine (SF-FSM) model is defined to describe multiple request-response packet pair sequence signatures of various applications using the same protocol. An inverted index of keywords in an industrial protocol is also proposed to accomplish fast state sequence matching. Then we put forward the concept of scenario reconstruction, using state sequence matching based on SF-FSM, to present the known vulnerabilities corresponding to applications of a specific type and version by identifying the packet interaction characteristics from the data flow in the supervisory control layer network. We also implement an anomaly detection approach to identifying illegal access using state sequence matching based on SF-FSM. An anomaly is asserted if none of the state sequence signatures in the SF-FSM is matched with a packet flow. Ultimately, an example based on industrial protocols is demonstrated by a prototype system to validate the methods of scenario reconstruction and anomaly detection.
Weighted-DESYNC and Its Application to End-to-End Throughput Fairness in Wireless Multihop Network
Authors: Yu Ui-Seong , Jung Ji-Young , Kong Eutteum , Choi HyungSeok , Lee Jung-Ryun
Published: April 2017

The end-to-end throughput of a routing path in wireless multihop network is restricted by a bottleneck node that has the smallest bandwidth among the nodes on the routing path. In this study, we propose a method for resolving the bottleneck-node problem in multihop networks, which is based on multihop DESYNC (MH-DESYNC) algorithm that is a bioinspired resource allocation method developed for use in multihop environments and enables fair resource allocation among nearby (up to two hops) neighbors. Based on MH-DESYNC, we newly propose weighted-DESYNC (W-DESYNC) as a tool artificially to control the amount of resource allocated to the specific user and thus to achieve throughput fairness over a routing path. Proposed W-DESYNC employs the weight factor of a link to determine the amount of bandwidth allocated to a node. By letting the weight factor be the link quality of a routing path and making it the same across a routing path via Cucker-Smale flocking model, we can obtain throughput fairness over a routing path. The simulation results show that the proposed algorithm achieves throughput fairness over a routing path and can increase total end-to-end throughput in wireless multihop networks.