bluuebunny/crossref_metadata_2025_split huggingface dataset:
APPROX-NoC
Authors: Boyapati Rahul , Huang Jiayi , Majumder Pritam , Yum Ki Hwan , Kim Eun Jung 
Published: September 2017

The trend of unsustainable power consumption and large memory bandwidth demands in massively parallel multicore systems, with the advent of the big data era, has brought upon the onset of alternate computation paradigms utilizing heterogeneity, specialization, processor-in-memory and approximation. Approximate Computing is being touted as a viable solution for high performance computation by relaxing the accuracy constraints of applications. This trend has been accentuated by emerging data intensive applications in domains like image/video processing, machine learning and big data analytics that allow inaccurate outputs within an acceptable variance. Leveraging relaxed accuracy for high throughput in Networks-on-Chip (NoCs), which have rapidly become the accepted method for connecting a large number of on-chip components, has not yet been explored. We propose APPROX-NoC, a hardware data approximation framework with an online data error control mechanism for high performance NoCs. APPROX-NoC facilitates approximate matching of data patterns, within a controllable value range, to compress them thereby reducing the volume of data movement across the chip.
Our evaluation shows that APPROX-NoC achieves on average up to 9% latency reduction and 60% throughput improvement compared with state-of-the-art NoC data compression mechanisms, while maintaining low application error. Additionally, with a data intensive graph processing application we achieve a 36.7% latency reduction compared to state-of-the-art compression mechanisms.
Macropinocytosis of Bevacizumab by Glioblastoma Cells in the Perivascular Niche Affects their Survival
Authors: Müller-Greven Gaëlle , Carlin Cathleen R. , Burgett Monica E. , Ahluwalia Manmeet S. , Lauko Adam , Nowacki Amy S. , Herting Cameron J. , Qadan Maha A. , Bredel Markus , Toms Steven A. , Lathia Justin D. , Hambardzumyan Dolores , Sarkaria Jann N. , Hamerlik Petra , Gladson Candece L. 
Published: September 2017

Abstract
Purpose: Bevacizumab, a humanized monoclonal antibody to VEGF, is used routinely in the treatment of patients with recurrent glioblastoma (GBM). However, very little is known regarding the effects of bevacizumab on the cells in the perivascular space in tumors.
Experimental Design: Established orthotopic xenograft and syngeneic models of GBM were used to determine entry of monoclonal anti-VEGF-A into, and uptake by cells in, the perivascular space. Based on the results, we examined CD133+ cells derived from GBM tumors in vitro. Bevacizumab internalization, trafficking, and effects on cell survival were analyzed using multilabel confocal microscopy, immunoblotting, and cytotoxicity assays in the presence/absence of inhibitors.
Results: In the GBM mouse models, administered anti-mouse-VEGF-A entered the perivascular tumor niche and was internalized by Sox2+/CD44+ tumor cells. In the perivascular tumor cells, bevacizumab was detected in the recycling compartment or the lysosomes, and increased autophagy was found. Bevacizumab was internalized rapidly by CD133+/Sox2+-GBM cells in vitro through macropinocytosis with a fraction being trafficked to a recycling compartment, independent of FcRn, and a fraction to lysosomes. Bevacizumab treatment of CD133+ GBM cells depleted VEGF-A and induced autophagy thereby improving cell survival. An inhibitor of lysosomal acidification decreased bevacizumab-induced autophagy and increased cell death. Inhibition of macropinocytosis increased cell death, suggesting macropinocytosis of bevacizumab promotes CD133+ cell survival.
Conclusions: We demonstrate that bevacizumab is internalized by Sox2+/CD44+-GBM tumor cells residing in the perivascular tumor niche. Macropinocytosis of bevacizumab and trafficking to the lysosomes promotes CD133+ cell survival, as does the autophagy induced by bevacizumab depletion of VEGF-A. Clin Cancer Res; 23(22); 7059–71. ©2017 AACR.
Enhanced Cancer Immunotherapy by Chimeric Antigen Receptor–Modified T Cells Engineered to Secrete Checkpoint Inhibitors
Authors: Li Si , Siriwon Natnaree , Zhang Xiaoyang , Yang Shuai , Jin Tao , He Feng , Kim Yu Jeong , Mac John , Lu Zhengfei , Wang Sijie , Han Xiaolu , Wang Pin 
Published: September 2017

Abstract
Purpose: Despite favorable responses of chimeric antigen receptor (CAR)-engineered T-cell therapy in patients with hematologic malignancies, the outcome has been far from satisfactory in the treatment of solid tumors, partially owing to the development of an immunosuppressive tumor microenvironment. To overcome this limitation, we engineered CAR T cells secreting checkpoint inhibitors (CPI) targeting PD-1 (CAR.αPD1-T) and evaluated their efficacy in a human lung carcinoma xenograft mouse model.
Experimental Design: To evaluate the effector function and expansion capacity of CAR.αPD1-T cells in vitro, we measured the production of IFNγ and T-cell proliferation following antigen-specific stimulation. Furthermore, the antitumor efficacy of CAR.αPD1-T cells, CAR T cells, and CAR T cells combined with anti–PD-1 antibody was determined using a xenograft mouse model. Finally, the underlying mechanism was investigated by analyzing the expansion and functional capacity of TILs.
Results: Human anti–PD-1 CPIs secreted by CAR.αPD1-T cells efficiently bound to PD-1 and reversed the inhibitory effect of PD-1/PD-L1 interaction on T-cell function. PD-1 blockade by continuously secreted anti–PD-1 attenuated the inhibitory T-cell signaling and enhanced T-cell expansion and effector function both in vitro and in vivo. In the xenograft mouse model, we demonstrated that the secretion of anti–PD-1 enhanced the antitumor activity of CAR T cells and prolonged overall survival.
Conclusions: With constitutive anti–PD-1 secretion, CAR.αPD1-T cells are more functional and expandable, and more efficient at tumor eradication than parental CAR T cells. Collectively, our study presents an important and novel strategy that enables CAR T cells to achieve better antitumor immunity, especially in the treatment of solid tumors. Clin Cancer Res; 23(22); 6982–92. ©2017 AACR.
Customized Viral Immunotherapy for HPV-Associated Cancer
Authors: Atherton Matthew J. , Stephenson Kyle B. , Pol Jonathan , Wang Fuan , Lefebvre Charles , Stojdl David F. , Nikota Jake K. , Dvorkin-Gheva Anna , Nguyen Andrew , Chen Lan , Johnson-Obaseki Stephanie , Villeneuve Patrick J. , Diallo Jean-Simon , Dimitroulakos Jim , Wan Yonghong , Lichty Brian D. 
Published: September 2017

Abstract
The viral-transforming proteins E6 and E7 make human papillomavirus–positive (HPV+) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multifunctional CD8+ T-cell responses. Boosting with MG1-E6E7 significantly increased the magnitude of T-cell responses compared with mice treated with a priming vaccine alone (greater than 50 × 106 E7-specific CD8+ T cells per mouse was observed, representing a 39-fold mean increase in boosted animals). MG1-E6E7 vaccination in the HPV+ murine model TC1 clears large tumors in a CD8+-dependent manner and results in durable immunologic memory. MG1-Maraba can acutely alter the tumor microenvironment in vivo and exploit molecular hallmarks of HPV+ cancer, as demonstrated by marked infection of HPV+ patient tumor biopsies and is, therefore, ideally suited as an oncolytic treatment against clinical HPV+ cancer. This approach has the potential to be directly translatable to human clinical oncology to tackle a variety of HPV-associated neoplasms that cause significant morbidity and mortality globally. Cancer Immunol Res; 5(10); 847–59. ©2017 AACR.
Representativity of the genus Asphondylia Loew, 1850 (Diptera, Cecidomyiidae) in Brazil
Authors: Flor Ismael Cividini , Maia Valéria Cid 
Published: September 2017

Representativity of the genus Asphondylia Loew, 1850 (Diptera, Cecidomyiidae) in Brazil. This cosmopolitan genus includes 272 galling species described, of which about 100 occur in the Neotropical Region. The present study goal to evaluate the richness of Asphondylia in Brazil, to provide an updated list of the host plant species, to determine the plant organs where galls are induced, to update the geographic distribution of the genus, to verify it distribution in the Brazilian biomes, and to the list the associated fauna. The survey data was carried out by consulting the Cecidomyiidae collection of the Museu Nacional/UFRJ, the database “Web of Science” using Asphondylia and Brasil/Brazil as keywords, 51 Brazilian inventories and two catalogues. Asphondylia is represented by 58 species in Brazil, among them, twenty are already known and 38 are still undetermined. The Brazilian described species represent 8% of the total of known species of Asphondylia in the world and 21% of species of the Neotropical fauna. This genus is associated with 51 plant species and 20 plant families in Brazil. Asteraceae comprise the greatest richness of Asphondylia species. This genus was found in five biomes, among them the Atlantic forest has the highest species richness. The associated fauna comprises parasitoids (Hymenoptera) and inquilines (Lepidoptera, Coleoptera and Diptera).
Novel Pathological Role of hnRNPA1 (Heterogeneous Nuclear Ribonucleoprotein A1) in Vascular Smooth Muscle Cell Function and Neointima Hyperplasia
Authors: Zhang Li , Chen Qishan , An Weiwei , Yang Feng , Maguire Eithne Margaret , Chen Dan , Zhang Cheng , Wen Guanmei , Yang Mei , Dai Bin , Luong Le Anh , Zhu Jianhua , Xu Qingbo , Xiao Qingzhong 
Published: September 2017

Objective—
hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1) plays a variety of roles in gene expression. However, little is known about the functional involvement of hnRNPA1 in vascular smooth muscle cell (VSMC) function and neointima hyperplasia. In this study, we have attempted to investigate the functional roles of hnRNPA1 in the contexts of VSMC function, injury-induced vessel remodeling, and human atherosclerotic lesions, as well as discern the molecular mechanisms involved.

Approach and Results—
hnRNPA1 expression levels were consistently modulated during VSMC phenotype switching and neointimal lesion formation induced by wire injury. Functional studies showed that VSMC-specific gene expression, proliferation, and migration were regulated by hnRNPA1. Our data show that hnRNPA1 exerts its effects on VSMC functions through modulation of IQGAP1 (IQ motif containing GTPase activating protein 1). Mechanistically, hnRNPA1 regulates IQGAP1 mRNA degradation through 2 mechanisms: upregulating microRNA-124 (miR-124) and binding to AU-rich element of IQGAP1 gene. Further evidence suggests that hnRNPA1 upregulates miR-124 by modulating miR-124 biogenesis and that IQGAP1 is the authentic target gene of miR-124. Importantly, ectopic overexpression of hnRNPA1 greatly reduced VSMC proliferation and inhibited neointima formation in wire-injured carotid arteries. Finally, lower expression levels of hnRNPA1 and miR-124, while higher expression levels of IQGAP1, were observed in human atherosclerotic lesions.

Conclusions—
Our data show that hnRNPA1 is a critical regulator of VSMC function and behavior in the context of neointima hyperplasia, and the hnRNPA1/miR-124/IQGAP1 regulatory axis represents a novel therapeutic target for the prevention of cardiovascular diseases.
Clinical Yield of Familial Screening After Sudden Death in Young Subjects
Authors: Quenin Pauline , Kyndt Florence , Mabo Philippe , Mansourati Jacques , Babuty Dominique , Thollet Aurélie , Guyomarch Béatrice , Redon Richard , Barc Julien , Schott Jean-Jacques , Sacher Frederic , Probst Vincent , Gourraud Jean Baptiste 
Published: September 2017

Background:
After sudden cardiac death with negative autopsy, clinical screening of relatives identifies a high proportion of inherited arrhythmia syndrome. However, the efficacy of this screening in families not selected by autopsy has never been assessed. We aim to investigate the value of clinical screening in relatives of all subjects who died suddenly before 45 years of age.

Methods and results:

One hundred and three consecutive families who experienced unexplained sudden cardiac death before 45 years of age were included from May 2009 to December 2014 in a prospective multicenter registry. Clinical screening was provided to all relatives and performed in 64 families (230 relatives, 80 unexplained sudden cardiac death). Diagnosis was established in 16 families (25%), including Brugada syndrome (7), long QT syndromes (5), dilated cardiomyopathy (2), and hypertrophic cardiomyopathy (2). The diagnostic yield was mainly dependent on the number of screened relatives (3.8±3.4 screened relatives in diagnosed families versus 2.0±1.5;
P
<0.005) rising to 47% with at least 3 relatives. It additionally increased from 3 of 32 (9%) to 9 of 22 (41%) when both parents were screened (
P
=0.01). Diagnostic performance was also dependent on the exhaustiveness of screening (70% of complete screening in the diagnosed families versus 25%;
P
<0.0001) with 17 Brugada syndromes and 15 long QT syndromes diagnosed based on pharmacological tests.

Conclusions:
Even without autopsy, familial screening after sudden death in young patients is effective. Broad screening of relatives and systematic tests, including pharmacological challenges, greatly increases the likelihood of diagnosis in families.
NOD2 (Nucleotide-Binding Oligomerization Domain 2) Is a Major Pathogenic Mediator of Coxsackievirus B3-Induced Myocarditis
Authors: Tschöpe Carsten , Müller Irene , Xia Yu , Savvatis Konstantinos , Pappritz Kathleen , Pinkert Sandra , Lassner Dirk , Heimesaat Markus M. , Spillmann Frank , Miteva Kapka , Bereswill Stefan , Schultheiss Heinz-Peter , Fechner Henry , Pieske Burkert , Kühl Uwe , Van Linthout Sophie 
Published: September 2017

Background:
The cytoplasmatic pattern recognition receptor, NOD2 (nucleotide-binding oligomerization domain 2), belongs to the innate immune system and is among others responsible for the recognition of single-stranded RNA. With Coxsackievirus B3 (CVB3) being a single-stranded RNA virus, and the recent evidence that the NOD2 target, NLRP3 (NOD-like receptor family, pyrin domain containing 3) is of importance in the pathogenesis of CVB3-induced myocarditis, we aimed to unravel the role of NOD2 in CVB3-induced myocarditis.

Methods and Results:

Endomyocardial biopsy NOD2 mRNA expression was higher in CVB3-positive patients compared with patients with myocarditis but without evidence of persistent CVB3 infection. Left ventricular NOD2 mRNA expression was also induced in CVB3-induced myocarditis versus healthy control mice. NOD2 knockdown
(−/−
)
mice were rescued from the detrimental CVB3-mediated effects as shown by a reduced cardiac inflammation (less cardiac infiltrates and suppression of proinflammatory cytokines), cardiac fibrosis, apoptosis, lower CAR (Coxsackievirus and adenovirus receptor) expression and CVB3 copy number, and an improved left ventricular function in NOD2
−/−
CVB3 mice compared with wild-type CVB3 mice. In agreement, NOD2
−/−
decreased the CVB3-induced inflammatory response, CVB3 copy number, and apoptosis in vitro. NOD2
−/−
was further associated with a reduction in CVB3-induced NLRP3 expression and activity as evidenced by lower ASC (apoptosis-associated speck-like protein containing a CARD) expression, caspase 1 activity, or IL-1β (interleukin-1β) protein expression under in vivo and in vitro CVB3 conditions.

Conclusions:
NOD2 is an important mediator in the viral uptake and inflammatory response during the pathogenesis of CVB3 myocarditis.
Preoperative Pectoralis Muscle Quantity and Attenuation by Computed Tomography Are Novel and Powerful Predictors of Mortality After Left Ventricular Assist Device Implantation
Authors: Teigen Levi M. , John Ranjit , Kuchnia Adam J. , Nagel Emily M. , Earthman Carrie P. , Kealhofer Jessica , Martin Cindy , Cogswell Rebecca 
Published: September 2017

Background:
Skeletal muscle mass decreases in end-stage heart failure and is predictive of clinical outcomes in several disease states. Skeletal muscle attenuation and quantity as quantified on preoperative chest computed tomographic scans may be predictive of mortality after continuous flow (CF) left ventricular assist device (LVAD) implantation.

Methods and Results:

A single-center continuous flow-LVAD database (n=354) was used to identify patients with chest computed tomographies performed in the 3 months before LVAD implantation (n=143). Among patients with computed tomography data available, unilateral pectoralis muscle mass indexed to body surface area and attenuation (approximated by mean Hounsfield units [PHU
m
]) were measured in each patient with a high intrarater and inter-rater reliability (intraclass correlation coefficients 0.98 and 0.97, respectively). Multivariate Cox regression analyses were performed, censoring at cardiac transplantation, to assess the impact of preoperative pectoralis muscle index and pectoralis muscle mean Hounsfield unit on survival after LVAD implantation. Each unit increase in pectoralis muscle index was associated with a 27% reduction in the hazard of death after LVAD (adjusted hazard ratio, 0.73; 95% confidence interval, 0.58–0.92;
P
=0.007). Each 5-U increase in pectoralis muscle mean Hounsfield unit was associated with a 22% reduction in the hazard of death after LVAD (adjusted hazard ratio, 0.78; 95% confidence interval, 0.68–0.89;
P
<0.0001). Pectoralis muscle index and pectoralis muscle mean Hounsfield unit outperformed other traditional measures in the data set, including the HeartMate II risk score.

Conclusions:
Pectoralis muscle size and attenuation were powerful predictors of outcomes after LVAD implantation in this data set. This one time, repeatable, internal assessment of patient substrate added valuable prognostic information that was not available on standard preoperative testing.
Diastolic Pressure Difference to Classify Pulmonary Hypertension in the Assessment of Heart Transplant Candidates
Authors: Wright Stephen P. , Moayedi Yasbanoo , Foroutan Farid , Agarwal Suhail , Paradero Geraldine , Alba Ana C. , Baumwol Jay , Mak Susanna 
Published: September 2017

Background:
The diastolic pressure difference (DPD) is recommended to differentiate between isolated postcapillary and combined pre-/postcapillary pulmonary hypertension (Cpc-PH) in left heart disease (PH-LHD). However, in usual practice, negative DPD values are commonly calculated, potentially related to the use of mean pulmonary artery wedge pressure (PAWP). We used the ECG to gate late-diastolic PAWP measurements. We examined the method’s impact on calculated DPD, PH-LHD subclassification, hemodynamic profiles, and mortality.

Methods and Results:

We studied patients with advanced heart failure undergoing right heart catheterization to assess cardiac transplantation candidacy (N=141). Pressure tracings were analyzed offline over 8 to 10 beat intervals. Diastolic pulmonary artery pressure and mean PAWP were measured to calculate the DPD as per usual practice (diastolic pulmonary artery pressure–mean PAWP). Within the same intervals, PAWP was measured gated to the ECG QRS complex to calculate the QRS-gated DPD (diastolic pulmonary artery pressure–QRS-gated PAWP). Outcomes occurring within 1 year were collected retrospectively from chart review. Overall, 72 of 141 cases demonstrated PH-LHD. Within PH-LHD, the QRS-gated DPD yielded higher calculated DPD values (3 [−1 to 6] versus 0 [−4 to 3] mm Hg;
P
<0.01) and a greater proportion of Cpc-PH (24% versus 8%;
P
<0.01) versus the usual practice DPD. Cases reclassified as Cpc-PH based on QRS-gated DPD demonstrated higher pulmonary arterial pressures versus isolated postcapillary pulmonary hypertension (
P
<0.05). One-year mortality was similar between PH-LHD groups.

Conclusions:
The DPD calculated in usual practice is underestimated in PH-LHD, which may classify Cpc-PH patients as isolated postcapillary pulmonary hypertension. The QRS-gated DPD reclassifies a subset of PH-LHD patients from isolated postcapillary pulmonary hypertension to Cpc-PH, which is characterized by an adverse hemodynamic profile.
Case Study and Climatological Analysis of Upper-Tropospheric Jet Stream and Stratosphere–Troposphere Exchanges Using VHF Profilers and Radionuclide Measurements in France
Authors: Baray Jean-Luc , Pointin Yves , Van Baelen Joël , Lothon Marie , Campistron Bernard , Cammas Jean-Pierre , Masson Olivier , Colomb Aurélie , Hervier Claude , Bezombes Yannick , Banson Sandra , Duroure Christophe , Hadad Dany , Tridon Frédéric 
Published: September 2017

AbstractThe authors present a climatological analysis of tropospheric horizontal wind profiles and jet stream events using long series of wind profiles from two VHF profilers located in France: Lannemezan (2001–14) and Opme (1999–2014). A case study of jet stream and stratospheric intrusion of air into the troposphere that occurred in January 2013 is first described and demonstrates the capability of the VHF profilers to detect jet stream events. The climatology study over the two sites reveals the strongest values of seasonal wind during winter (21.4 m s−1at 8.7-km height at Opme; 25.1 m s−1at 9.6-km height at Lannemezan). A methodology based on the automatic detection of maximum winds on a decadal series of hourly wind profiles allows the detection of jet stream events and establishes its climatology for each site. A frequency analysis of jet stream events of westerly winds over 50 m s−1presents a clear seasonality at the two sites, with a maximum in winter (3.5%–9.7% of hourly profiles) and a minimum in summer (near 1%). Cosmogenic radionuclides sampled at Opme also exhibit a clear seasonal variation with maximum in spring and minimum in the cold seasons; the7Be/22Na activity ratio confirms stratosphere-to-troposphere exchanges for the studied cases. The mean interannual variability of the frequency of jet stream events is 1.5% in Opme and 2.9% in Lannemezan. Positive decadal trends are observed for the two sites: +1.6 ± 1.2% decade−1for Opme and +2.4 ± 2.2% decade−1for Lannemezan.