bluuebunny/crossref_metadata_2025_split huggingface dataset:
Boltzmann–Curtiss Description for Flows Under Translational Nonequilibrium
Authors: Ahmed Mohamed M. , Cheikh Mohamad I. , Chen James 
Published: December 2019

Abstract
Continuum-based theories, such as Navier–Stokes (NS) equations, have been considered inappropriate for flows under nonequilibrium conditions. In part, it is due to the lack of rotational degrees-of-freedom in the Maxwell–Boltzmann distribution. The Boltzmann–Curtiss formulation describes gases allowing both rotational and translational degrees-of-freedom and forms morphing continuum theory (MCT). The first-order solution to Boltzmann–Curtiss equation yields a stress tensor that contains a coupling coefficient that is dependent on the particles number density, the temperature, and the total relaxation time. A new bulk viscosity model derived from the Boltzmann–Curtiss distribution is employed for shock structure and temperature profile under translational and rotational nonequilibrium. Numerical simulations of argon and nitrogen shock profiles are performed in the Mach number range of 1.2–9. The current study, when comparing with experimental measurements and direct simulation Monte Carlo (DSMC) method, shows a significant improvement in the density profile, normal stresses, and shock thickness at nonequilibrium conditions than NS equations. The results indicate that equations derived from the Boltzmann–Curtiss distribution are valid for a wide range of nonequilibrium conditions than those from the Maxwell–Boltzmann distribution.
Slurry Erosion Performance of Ni + B4C Microwave Composite Clads
Authors: Minhaj M. , Singh Bhupinder , Zafar Sunny 
Published: December 2019

Abstract
A composite clad of Ni-based alloy and B4C was developed on austenitic steel substrate through microwave hybrid heating. The B4C was added with Ni-based alloy powder in various weight proportions (0%, 5%, 10%, and 20%). The clads were investigated for the microstructural details, nanohardness and slurry erosion performance. Silt collected from river Uhl was used as the erodent for the slurry erosion test. Slurry erosion performance of the clads was evaluated at an impact angle of 90 deg and jet velocity of 40 m/s. Microstructural characterization confirms the uniform distribution of hard (boride and carbide) phases in the Ni-based matrix of the microwave composite clads. The presence of hard phases in the Ni-based matrix enhanced the slurry erosion resistance performance.
Recent density decline in wild-collected subarctic crustose coralline algae reveals climate change signature
Authors: Chan P.T.W. , Halfar J. , Adey W.H. , Lebednik P.A. , Steneck R. , Norley C.J.D. , Holdsworth D.W. 
Published: December 2019

AbstractWarming surface ocean temperatures combined with the continued diffusion of atmospheric CO2 into seawater have been shown to have detrimental impacts on calcareous marine organisms in tropical and temperate localities. However, greater oceanic CO2 uptake in higher latitudes may present a higher oceanic acidification risk to carbonate organisms residing in Arctic and subarctic habitats. This is especially true for crustose coralline algae that build their skeletons using high-Mg calcite, which is among the least stable and most soluble of the carbonate minerals. Here we present a century-long annually resolved growth, density, and calcification rate record from the crustose coralline alga Clathromorphum nereostratum, a dominant calcifier in Pacific Arctic and subarctic benthic communities. Specimens were collected from the Aleutian Islands, Alaska (USA), a region that has undergone a long-term decline of 0.08 ± 0.01 pH units since the late 19th century. Growth and calcification rates remain relatively stable throughout the record, but skeletal densities have declined substantially since A.D. 1983. Strong correlations to warming sea-surface temperatures indicate that temperature stress may play a significant role in influencing the ability of corallines to calcify. Decreasing algal skeletal density may offset the benefits of continued growth and calcification due to a weakening in structural integrity, which could have detrimental consequences for the diverse reef-like communities associated with algal structures in mid-to-high latitudes.
Triple oxygen isotope variations in magnetite from iron-oxide deposits, central Iran, record magmatic fluid interaction with evaporite and carbonate host rocks
Authors: Peters Stefan T.M. , Alibabaie Narges , Pack Andreas , McKibbin Seann J. , Raeisi Davood , Nayebi Niloofar , Torab Farhad , Ireland Trevor , Lehmann Bernd 
Published: December 2019

Abstract
Oxygen isotope ratios in magnetite can be used to study the origin of iron-oxide ore deposits. In previous studies, only 18O/16O ratios of magnetite were determined. Here, we report triple O isotope data (17O/16O and 18O/16O ratios) of magnetite from the iron-oxide–apatite (IOA) deposits of the Yazd and Sirjan areas in central Iran. In contrast to previous interpretations of magnetite from similar deposits, the triple O isotope data show that only a few of the magnetite samples potentially record isotopic equilibrium with magma or with pristine magmatic water (H2O). Instead, the data can be explained if magnetite had exchanged O isotopes with fluids that had a mass-independently fractionated O isotope composition (i.e., MIF-O), and with fluids that had exchanged O isotopes with marine sedimentary carbonate rocks. The MIF-O signature of the fluids was likely obtained by isotope exchange with evaporite rocks of early Cambrian age that are associated with the IOA deposits in central Iran. In order to explain the triple O isotope composition of the magnetite samples in conjunction with available iron isotope data for magnetite from the deposits, we propose that magnetite formed from magmatic fluids that had interacted with evaporite and carbonate rocks at high temperatures and at variable water/rock ratios; e.g., magmatic fluids that had been released into the country rocks of a magma reservoir. Additionally, the magnetite could have formed from magmatic fluids that had exchanged O isotopes with SO2 and CO2 that, in turn, had been derived by the magmatic assimilation and/or metamorphic breakdown of evaporite and carbonate rocks.
Higher aqueous levels of matrix metalloproteinases indicated visual impairment in patients with retina vein occlusion after anti-VEGF therapy
Authors: Luo Yong , Wan Jianbo , Luo Chang , Liu HengWei , Zhou YuFan , Xu Heping , Chen Zhongping 
Published: December 2019

PurposeTo investigate the levels of matrix metalloproteinases (MMPs) in aqueous humour of patients with retinal vein occlusion (RVO) and the relationship between intraocular MMP levels and retinal lesion and visual prognosis.Materials and methods52 RVO patients, including 23 with central retinal vein occlusion (CRVO) and 29 with branch retinal vein occlusion (BRVO) and 20 participants with senile cataract were enrolled in this study. Retinal lesions were examined by fundus colour photography, fluorescein fundus angiography and optical coherence tomographic angiography. Sixty microliters of aqueous humour were collected during intravitreal anti-Vascular Endothelial Growth Factor (VEGF) injection or cataract surgery. The aqueous levels of MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10 were measured using the Luminex xMAP multiplex assay. The relationship between MMP levels and clinical presentations was analysed by Pearson correlation test.ResultsThe aqueous humour levels of MMP-1, MMP-2, MMP-7 and MMP-9, but not MMP10 in RVO patients were significantly higher than those in people with cataract after adjusting for age. Further analysis of RVO subgroups showed that the aqueous humour level of MMP2 in CRVO was significantly higher than that in BRVO. The aqueous humour levels of MMP-1 and MMP-2 were positively correlated with superficial capillary plexus vessel density (SVD), whereas the aqueous humour levels of MMP-1 and MMP-7 were negatively correlated with visual improvement following treatment. No correlation between aqueous humour levels of MMP and disease duration and central retinal thickness was observed.ConclusionsRVO eyes had significantly higher intraocular levels of MMP-1, MMP-2, MMP-7 and MMP-9 than cataract eyes and the level of MMP2 appears to be related to the area of occlusion. Intraocular levels of MMP may positively affect SVD and negatively impact visual function in RVO.
Routine induction in late-term pregnancies: follow-up of a Danish induction of labour paradigm
Authors: Rydahl Eva , Declercq Eugene , Juhl Mette , Maimburg Rikke Damkjær 
Published: December 2019

ObjectivesFor many years, routine elective induction of labour at gestational week (GW) 42+0 has been recommended in Denmark. In 2011, a more proactive protocol was introduced aimed at reducing stillbirths, and practice changed into earlier routine induction, i.e. between 41+3 and 41+5 GW. The present study evaluates a national change in induction of labour regime. The trend of maternal and neonatal consequences are monitored in the preintervention period (2000–2010) compared with the postintervention period (2012–2016).DesignA national retrospective register-based cohort study.SettingDenmark.ParticipantsAll births in Denmark 41+3 to 45+0 GWs between 2000 and 2016 (N = 152 887).Outcome measuresPrimary outcomes: stillbirths, perinatal death, and low Apgar scores. Additional outcomes: birth interventions and maternal outcomes.ResultsFor the primary outcomes, no differences in stillbirths, perinatal death, and low Apgar scores were found comparing the preintervention and postintervention period. Of additional outcomes, the trend changed significantly postintervention concerning use of augmentation of labour, epidural analgesia, induction of labour and uterine rupture (all p<0.05). There was no significant change in the trend for caesarean section and instrumental birth. Most notable for clinical practice was the increase in induction of labour from 41% to 65% (p<0.01) at 41+3 weeks during 2011 as well as the rare occurrence of uterine ruptures (from 2.6 to 4.2 per thousand, p<0.02).ConclusionsEvaluation of a more proactive regimen recommending induction of labour from GW 41+3 compared with 42+0 using national register data found no differences in neonatal outcomes including stillbirth. The number of women with induced labour increased significantly.
Tobacco industry access to policy elites and the implementation of Article 5.3 of the WHO Framework Convention on Tobacco Control
Authors: Willemsen Marc C , Fooks Gary 
Published: December 2019

IntroductionArticle 5.3 WHO Framework Convention on Tobacco Control (FCTC) aims to prevent tobacco industry interference with public health policy. The degree of protection depends on several factors: the interpretation of Article 5.3 by governments; the presence of codes of practice; and the effectiveness of industry lobbying versus public health advocacy. We examine these factors with reference to the Dutch government’s interpretation of Article 5.3.MethodsWe searched the Dutch Tobacco Industry Special Collection, part of the Truth Tobacco Industry Documents archive, containing more than 1100 Dutch government documents.ResultsBetween 2007 and 2012, under consistent pressure from the industry, an initial strict view of Article 5.3 gave way to increased contact with the industry. The industry tried to shift the governance of tobacco policy back to the Ministry of Economic Affairs. Around 2010, Dutch public health advocates began to use Article 5.3. Efforts included naming and shaming government contact with the industry, parliamentary questions about industry–government contact, a report outlining how Article 5.3 should be observed and, most importantly, a court case. In response to this, the government produced a formal code of practice, which was used to prevent industry involvement in the development of a new National Prevention Accord.DiscussionThe Dutch government’s initial decision not to codify Article 5.3 created an administrative environment in which health ministers’ interpretation of Article 5.3 was able to shift according to their political beliefs. The findings support the recommendation that Parties to the FCTC take a strict approach and formally codify Article 5.3 to ensure effective implementation.
Weak and strong deflection gravitational lensing by a renormalization group improved Schwarzschild black hole
Authors: Lu Xu , Xie Yi 
Published: December 2019

AbstractWeak and strong deflection gravitational lensing by a renormalization group improved Schwarzschild black hole is investigated and its observables are found. By taking the supermassive black holes Sgr A* and M87* respectively in the Galactic Center and at the center of M87 as lenses, we estimate these observables and analyse possibility of detecting this quantum improvement. It is not feasible to distinguish such a black hole by most observables in the near future except for the apparent size of the shadow. We also note that directly using measured shadow of M87* to constrain this quantum effect requires great care.
HPV16 E5 Mediates Resistance to PD-L1 Blockade and Can Be Targeted with Rimantadine in Head and Neck Cancer
Authors: Miyauchi Sayuri , Sanders P. Dominick , Guram Kripa , Kim Sangwoo S. , Paolini Francesca , Venuti Aldo , Cohen Ezra E.W. , Gutkind J. Silvio , Califano Joseph A. , Sharabi Andrew B. 
Published: December 2019

AbstractThere is a critical need to understand mechanisms of resistance and to develop combinatorial strategies to improve responses to checkpoint blockade immunotherapy (CBI). Here, we uncover a novel mechanism by which the human papillomavirus (HPV) inhibits the activity of CBI in head and neck squamous cell carcinoma (HNSCC). Using orthotopic HNSCC models, we show that radiation combined with anti–PD-L1 immunotherapy significantly enhanced local control, CD8+ memory T cells, and induced preferential T-cell homing via modulation of vascular endothelial cells. However, the HPV E5 oncoprotein suppressed immune responses by downregulating expression of major histocompatibility complex and interfering with antigen presentation in murine models and patient tumors. Furthermore, tumors expressing HPV E5 were rendered entirely resistant to anti–PD-L1 immunotherapy, and patients with high expression of HPV16 E5 had worse survival. The antiviral E5 inhibitor rimantadine demonstrated remarkable single-agent antitumor activity. This is the first report that describes HPV E5 as a mediator of resistance to anti–PD-1/PD-L1 immunotherapy and demonstrates the antitumor activity of rimantadine. These results have broad clinical relevance beyond HNSCC to other HPV-associated malignancies and reveal a powerful mechanism of HPV-mediated immunosuppression, which can be exploited to improve response rates to checkpoint blockade.Significance:This study identifies a novel mechanism of resistance to anti–PD-1/PD-L1 immunotherapy mediated by HPV E5, which can be exploited using the HPV E5 inhibitor rimantadine to improve outcomes for head and neck cancer patients.
Tim-3 Hampers Tumor Surveillance of Liver-Resident and Conventional NK Cells by Disrupting PI3K Signaling
Authors: Tan Siyu , Xu Yong , Wang Zehua , Wang Tixiao , Du Xianhong , Song Xiaojia , Guo Xiaowei , Peng Jiali , Zhang Jie , Liang Yan , Lu Jinghui , Peng Jun , Gao Chengjiang , Wu Zhuanchang , Li Chunyang , Li Nailin , Gao Lifen , Liang Xiaohong , Ma Chunhong 
Published: December 2019

Abstract

Natural killer (NK) cells are enriched within the liver. Apart from conventional NK (cNK) cells, recent studies identified a liver-resident NK (LrNK) subset, which constitutes about half of hepatic NK cells and exhibits distinct developmental, phenotypic, and functional features. However, it remains unclear whether and how LrNK cells, as well as cNK cells, participate in the development of hepatocellular carcinoma (HCC) individually. Here, we report that both LrNK and cNK cells are significantly decreased in HCC. The T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) was significantly upregulated in both tumor-infiltrating LrNK and cNK cells and suppressed their cytokine secretion and cytotoxic activity. Mechanistically, phosphatidylserine (PtdSer) engagement promoted phosphorylation of Tim-3, which then competed with PI3K p110 to bind p85, inhibiting downstream Akt/mTORC1 signaling and resulting in malfunctioning of both NK-cell subsets. Tim-3 blockade retarded HCC growth in a NK-cell–dependent manner. These studies for the first time report the presence and dysfunction of LrNK cells in HCC and show that Tim-3–mediated PI3K/mTORC1 interference is responsible for the dysfunction of both tumor-infiltrating cNK and LrNK cells, providing a new strategy for immune checkpoint-based targeting.

Significance:
Tim-3 enhances hepatocellular carcinoma growth by blocking natural killer cell function.
Primary Preclinical and Clinical Evaluation of 68Ga-DOTA-TMVP1 as a Novel VEGFR-3 PET Imaging Radiotracer in Gynecological Cancer
Authors: Li Fei , Zhang Zhenzhong , Cai Jiong , Chen Xi , Zhou Ying , Ma Xiangyi , Dong Qingjian , Li Fang , Xi Ling 
Published: December 2019

Abstract

Purpose:
Tumor periphery and lymph nodes of tumor-induced lymphangiogenesis often abundantly express VEGFR-3. In our previous study, we identified a 5-amino acid peptide named TMVP1, which binds specifically to VEGFR-3. The objective of this study was to develop a novel 68Ga-labeled TMVP1 for VEGFR-3 PET imaging and to investigate its safety, biodistribution, and tumor-localizing efficacy in xenograft tumor models and a small cohort of patients with recurrent ovarian and cervical cancer.

Experimental Design:
The DOTA-conjugated TMVP1 peptide was labeled with radionuclide 68Ga. SPR and saturation binding assays were used for the receptor-binding studies. Gynecologic xenograft tumors were employed for small-animal PET imaging and biodistribution of 68Ga-DOTA-TMVP1 in vivo. In the clinical study, 5 healthy volunteers and 8 patients with gynecologic cancer underwent whole-body PET/CT after being injected with 68Ga-DOTA-TMVP1.

Results:
DOTA-TMVP1 was successfully labeled with 68Ga. LECs showed higher binding capacity with 68Ga-DOTA-TMVP1 than LEC(shVEGFR-3) and human umbilical vein endothelial cells. In mice with subcutaneous C33-A and SKOV-3 xenografts, the tracer was rapidly eliminated through the kidney to the bladder, and the small-animal PET/CT helped to clearly visualize the tumors. In patients with recurrent ovarian cancer and cervical cancer, tracer accumulation well above the background level was demonstrated in most identified sites of disease; especially with recurrent endodermal sinus tumors, the diagnostic value of 68Ga-DOTA-TMVP1 was comparable with that of 18F-FDG PET/CT.

Conclusions:
68Ga-DOTA-TMVP1 is a potential PET tracer for imaging VEGFR-3 with favorable pharmacokinetics.
A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors
Authors: Varga Andrea , Soria Jean-Charles , Hollebecque Antoine , LoRusso Patricia , Bendell Johanna , Huang Shih-Min A. , Wagle Marie-Claire , Okrah Kwame , Liu Lichuan , Murray Elaine , Sanabria-Bohorquez Sandra M. , Tagen Michael , Dokainish Hatem , Mueller Lars , Burris Howard 
Published: December 2019

Abstract

Purpose:
ERK1/2 signaling can be dysregulated in cancer. GDC-0994 is an oral inhibitor of ERK1/2. A first-in-human, phase I dose escalation study of GDC-0994 was conducted in patients with locally advanced or metastatic solid tumors.

Patients and Methods:
GDC-0994 was administered once daily on a 21-day on/7-day off schedule to evaluate safety, pharmacokinetics, and preliminary signs of efficacy. Patients with pancreatic adenocarcinoma and BRAF-mutant colorectal cancer were enrolled in the expansion stage.

Results:
Forty-seven patients were enrolled in six successive cohorts (50–800 mg). A single DLT of grade 3 rash occurred at 600 mg. The most common drug-related adverse events (AE) were diarrhea, rash, nausea, fatigue, and vomiting. Pharmacokinetic data showed dose-proportional increases in exposure, with a mean half-life of 23 hours, supportive of once daily dosing. In evaluable paired biopsies, MAPK pathway inhibition ranged from 19% to 51%. Partial metabolic responses by FDG-PET were observed in 11 of 20 patients across dose levels in multiple tumor types. Overall, 15 of 45 (33%) patients had a best overall response of stable disease and 2 patients with BRAF-mutant colorectal cancer had a confirmed partial response.

Conclusions:
GDC-0994 had an acceptable safety profile and pharmacodynamic effects were observed by FDG-PET and in serial tumor biopsies. Single-agent activity was observed in 2 patients with BRAF-mutant colorectal cancer.
Targeting Protein Translation by Rocaglamide and Didesmethylrocaglamide to Treat MPNST and Other Sarcomas
Authors: Chang Long-Sheng , Oblinger Janet L. , Burns Sarah S. , Huang Jie , Anderson Larry W. , Hollingshead Melinda G. , Shen Rulong , Pan Li , Agarwal Garima , Ren Yulin , Roberts Ryan D. , O'Keefe Barry R. , Kinghorn A. Douglas , Collins Jerry M. 
Published: December 2019

Abstract

Malignant peripheral nerve sheath tumors (MPNST) frequently overexpress eukaryotic initiation factor 4F components, and the eIF4A inhibitor silvestrol potently suppresses MPNST growth. However, silvestrol has suboptimal drug-like properties, including a bulky structure, poor oral bioavailability (&lt;2%), sensitivity to MDR1 efflux, and pulmonary toxicity in dogs. We compared ten silvestrol-related rocaglates lacking the dioxanyl ring and found that didesmethylrocaglamide (DDR) and rocaglamide (Roc) had growth-inhibitory activity comparable with silvestrol. Structure–activity relationship analysis revealed that the dioxanyl ring present in silvestrol was dispensable for, but may enhance, cytotoxicity. Both DDR and Roc arrested MPNST cells at G2–M, increased the sub-G1 population, induced cleavage of caspases and PARP, and elevated the levels of the DNA-damage response marker γH2A.X, while decreasing the expression of AKT and ERK1/2, consistent with translation inhibition. Unlike silvestrol, DDR and Roc were not sensitive to MDR1 inhibition. Pharmacokinetic analysis confirmed that Roc had 50% oral bioavailability. Importantly, Roc, when administered intraperitoneally or orally, showed potent antitumor effects in an orthotopic MPNST mouse model and did not induce pulmonary toxicity in dogs as found with silvestrol. Treated tumors displayed degenerative changes and had more cleaved caspase-3–positive cells, indicative of increased apoptosis. Furthermore, Roc effectively suppressed the growth of osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma cells and patient-derived xenografts. Both Roc- and DDR-treated sarcoma cells showed decreased levels of multiple oncogenic kinases, including insulin-like growth factor-1 receptor. The more favorable drug-like properties of DDR and Roc and the potent antitumor activity of Roc suggest that these rocaglamides could become viable treatments for MPNST and other sarcomas.