bluuebunny/crossref_metadata_2025_split huggingface dataset:
Great Bear Snow Shed on the Coquihalla Highway, British Columbia, Canada
Authors: Nichol Douglas 
Published: September 2016

Canadians claim that the recently constructed Coquihalla Highway over the Rocky Mountains is one of the most spectacular and scenic superhighways in the world (Fig. 1). Unfortunately in winter snow avalanche activity is widespread and about 150 avalanche sites affect almost 17 km of the route. In one critical area a roof structure called the Great Bear Snow Shed has been constructed over the highway to protect traffic throughout the winter. This particular area of extreme avalanche hazard has a history of high avalanche frequency. Here heavy snowfall, steep terrain and adverse geological factors combine to create potentially unsafe ground above the road (Fig. 2).
The Coquihalla Highway is a four-lane dual carriage-way and the only tollway in British Columbia. It starts approximately 200 km east of Vancouver near the township of Hope on the Trans-Canada Highway and runs northeastwards for 195 km through Merritt to rejoin the Trans-Canada Highway at Kamloops. The new highway follows a series of mountain corridors through the rugged Cascade Ranges and thereby reduces the Hope-Kamloops travel distance by 80 km. The main corridors are primarily glacial in origin and contain extensive deposits of moraine and fluvioglacial drift in the valley bottoms. Along the route elevations greater than 1900 m are commonplace and relief may be as much as 1300 m. The annual snowfall in this part of the Cascade Range is usually less than 8 m, but in particularly cold years the snowpack may reach depths of more than 16 m. Extensive drifting during
Phreatomagmatic maar-diatreme volcanoes and their incremental growth: a model
Authors: Lorenz Volker , Suhr Peter , Suhr Stefan 
Published: September 2016

Abstract
We report here a growth model for phreatomagmatic maar-diatreme volcanoes with respect to the number of eruptions documented in the tephra beds of maar tephra rings and the upper bedded diatreme facies. We show that the number of tephra beds in large diatremes is larger than that in maar tephra rings. Base surges that lack sufficient momentum to scale high maar crater walls deposit their tephra only inside the crater. Thus the total number of eruptions at large maar-diatreme volcanoes will be larger than the number recorded in maar tephra rings. As many maar-diatreme volcanoes erupt dominantly accidental clasts, an incremental mathematical model was applied to study the growth of diatremes. The model is based only on the ejection of distinct amounts of accidental clasts per unit eruption and the chosen number of eruptions is assumed to be identical. The incremental growth of cone-shaped diatremes follows cube-root functions with respect to diameter and depth and slows down with ongoing eruptions. In nature, small and large maar-diatreme volcanoes are formed and filled syn-eruptively, mostly by tephra, depending on the duration and quantity of magma involved in phreatomagmatic eruptions. In our opinion, this mathematical model is the only current method able to model the growth of diatremes.
The Added Value of Circulating Tumor Cell Enumeration to Standard Markers in Assessing Prognosis in a Metastatic Castration-Resistant Prostate Cancer Population
Authors: Heller Glenn , Fizazi Karim , McCormack Robert , Molina Arturo , MacLean David , Webb Iain J. , Saad Fred , de Bono Johann S. , Scher Howard I. 
Published: September 2016

AbstractPurpose: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease for which better prognostic models for survival are needed. We examined the added value of circulating tumor cell (CTC) enumeration relative to common prognostic laboratory measures from patients with CRPC.Methods: Utility of CTC enumeration as a baseline and postbaseline prognostic biomarker was examined using data from two prospective randomized registration-directed trials (COU-AA-301 and ELM-PC4) within statistical models used to estimate risk for survival. Discrimination and calibration were used to measure model predictive accuracy and the added value for CTC enumeration in the context of a Cox model containing albumin, lactate dehydrogenase (LDH), PSA, hemoglobin, and alkaline phosphatase (ALK). Discrimination quantifies how accurately a risk model predicts short-term versus long-term survivors. Calibration measures the closeness of actual survival time to the predicted survival time.Results: Adding CTC enumeration to a model containing albumin, LDH, PSA, hemoglobin, and ALK (“ALPHA”) improved its discriminatory power. The weighted c-index for ALPHA without CTCs was 0.72 (SE, 0.02) versus 0.75 (SE, 0.02) for ALPHA + CTCs. The increase in discrimination was restricted to the lower-risk cohort. In terms of calibration, adding CTCs produced a more accurate model-based prediction of patient survival. The absolute prediction error for ALPHA was 3.95 months (SE, 0.28) versus 3.75 months (SE, 0.22) for ALPHA + CTCs.Conclusions: Addition of CTC enumeration to standard measures provides more accurate assessment of patient risk in terms of baseline and postbaseline prognosis in the mCRPC population. Clin Cancer Res; 23(8); 1967–73. ©2016 AACR.
A Novel Compound ARN-3236 Inhibits Salt-Inducible Kinase 2 and Sensitizes Ovarian Cancer Cell Lines and Xenografts to Paclitaxel
Authors: Zhou Jinhua , Alfraidi Albandri , Zhang Shu , Santiago-O'Farrill Janice M. , Yerramreddy Reddy Venkata Krishna , Alsaadi Abdulkhaliq , Ahmed Ahmed A. , Yang Hailing , Liu Jinsong , Mao Weiqun , Wang Yan , Takemori Hiroshi , Vankayalapati Hariprasad , Lu Zhen , Bast Robert C. 
Published: September 2016

Abstract
Purpose: Salt-inducible kinase 2 (SIK2) is a centrosome kinase required for mitotic spindle formation and a potential target for ovarian cancer therapy. Here, we examine the effects of a novel small-molecule SIK2 inhibitor, ARN-3236, on sensitivity to paclitaxel in ovarian cancer.
Experimental Design: SIK2 expression was determined in ovarian cancer tissue samples and cell lines. ARN-3236 was tested for its efficiency to inhibit growth and enhance paclitaxel sensitivity in cultures and xenografts of ovarian cancer cell lines. SIK2 siRNA and ARN-3236 were compared for their ability to produce nuclear–centrosome dissociation, inhibit centrosome splitting, block mitotic progression, induce tetraploidy, trigger apoptotic cell death, and reduce AKT/survivin signaling.
Results: SIK2 is overexpressed in approximately 30% of high-grade serous ovarian cancers. ARN-3236 inhibited the growth of 10 ovarian cancer cell lines at an IC50 of 0.8 to 2.6 μmol/L, where the IC50 of ARN-3236 was inversely correlated with endogenous SIK2 expression (Pearson r = −0.642, P = 0.03). ARN-3236 enhanced sensitivity to paclitaxel in 8 of 10 cell lines, as well as in SKOv3ip (P = 0.028) and OVCAR8 xenografts. In at least three cell lines, a synergistic interaction was observed. ARN-3236 uncoupled the centrosome from the nucleus in interphase, blocked centrosome separation in mitosis, caused prometaphase arrest, and induced apoptotic cell death and tetraploidy. ARN-3236 also inhibited AKT phosphorylation and attenuated survivin expression.
Conclusions: ARN-3236 is the first orally available inhibitor of SIK2 to be evaluated against ovarian cancer in preclinical models and shows promise in inhibiting ovarian cancer growth and enhancing paclitaxel chemosensitivity. Clin Cancer Res; 23(8); 1945–54. ©2016 AACR.
Ibrutinib Inhibits ERBB Receptor Tyrosine Kinases and HER2-Amplified Breast Cancer Cell Growth
Authors: Chen Jun , Kinoshita Taisei , Sukbuntherng Juthamas , Chang Betty Y. , Elias Laurence 
Published: September 2016

Abstract
Ibrutinib is a potent, small-molecule Bruton tyrosine kinase (BTK) inhibitor developed for the treatment of B-cell malignancies. Ibrutinib covalently binds to Cys481 in the ATP-binding domain of BTK. This cysteine residue is conserved among 9 other tyrosine kinases, including HER2 and EGFR, which can be targeted. Screening large panels of cell lines demonstrated that ibrutinib was growth inhibitory against some solid tumor cells, including those inhibited by other HER2/EGFR inhibitors. Among sensitive cell lines, breast cancer lines with HER2 overexpression were most potently inhibited by ibrutinib (&lt;100 nmol/L); in addition, the IC50s were lower than that of lapatinib and dacomitinib. Inhibition of cell growth by ibrutinib coincided with downregulation of phosphorylation on HER2 and EGFR and their downstream targets, AKT and ERK. Irreversible inhibition of HER2 and EGFR in breast cancer cells was established after 30-minute incubation above 100 nmol/L or following 2-hour incubation at lower concentrations. Furthermore, ibrutinib inhibited recombinant HER2 and EGFR activity that was resistant to dialysis and rapid dilution, suggesting an irreversible interaction. The dual activity toward TEC family (BTK and ITK) and ERBB family kinases was unique to ibrutinib, as ERBB inhibitors do not inhibit or covalently bind BTK or ITK. Xenograft studies with HER2+ MDA-MB-453 and BT-474 cells in mice in conjunction with determination of pharmacokinetics demonstrated significant exposure-dependent inhibition of growth and key signaling molecules at levels that are clinically achievable. Ibrutinib's unique dual spectrum of activity against both TEC family and ERBB kinases suggests broader applications of ibrutinib in oncology. Mol Cancer Ther; 15(12); 2835–44. ©2016 AACR.
ФІЗІОЛОГІЧНІ МЕХАНІЗМИ ДІЇ ПОЛІХРОМАТИЧНОГО ПОЛЯРИЗОВАНОГО СВІТЛА ПРИ УШКОДЖЕННЯХ ШКІРИ ВИСОКОЮ ТЕМПЕРАТУРОЮ
Authors: Gulyar S. O. , Strelchenko Yu. I. , Jelskyj V. M. 
Published: September 2016

We developed a valid experimental model of dosed burn to study the influence of polarized light on burns, obtained from open flame, with a possibility of their basic parameters regulation. In the article there are characterized the expression and peculiarities of inflammation reaction process, development and dynamics of granulation growth and the process of burn wound epithelization. We observed polarized light positive influence on burn wound regeneration and speed of its healing. In particular, we singled out: derma depth alteration restriction and secondary alteration of skin tissues and sub muscles, activation of mechanisms, that restrict inflammation, fibroblasts proliferation increase, formation of granulations and neo-angiogenesis, stimulation of proliferation, keratinocytes' migration and wound surface epithelialization under the influence of polarized light. We singled out expressed antinociceptive, anti-stress and adaptive-stimulating effects of polarized light on central nervous system functional state at burns.
Amelioration of X-Linked Related Autophagy Failure in Danon Disease With DNA Methylation Inhibitor
Authors: Ng Kwong-Man , Mok Pamela Y. , Butler Amy W. , Ho Jenny C.Y. , Choi Shing-Wan , Lee Yee-Ki , Lai Wing-Hon , Au Ka-Wing , Lau Yee-Man , Wong Lai-Yung , Esteban Miguel A. , Siu Chung-Wah , Sham Pak C. , Colman Alan , Tse Hung-Fat 
Published: September 2016

Background:
Danon disease is an X-linked disorder that leads to fatal cardiomyopathy caused by a deficiency in lysosome-associated membrane protein-2 (LAMP2). In female patients, a later onset and less severe clinical phenotype have been attributed to the random inactivation of the X chromosome carrying the mutant diseased allele. We generated a patient-specific induced pluripotent stem cell (iPSCs)–based model of Danon disease to evaluate the therapeutic potential of Xi-chromosome reactivation using a DNA methylation inhibitor.

Methods:

Using whole-exome sequencing, we identified a nonsense mutation (c.520C>T, exon 4) of the
LAMP2
gene in a family with Danon disease. We generated iPSC lines from somatic cells derived from the affected mother and her 2 sons, and we then differentiated them into cardiomyocytes (iPSC-CMs) for modeling the histological and functional signatures, including autophagy failure of Danon disease.

Results:

Our iPSC-CM platform provides evidence that random inactivation of the wild-type and mutant
LAMP2
alleles on the X chromosome is responsible for the unusual phenotype in female patients with Danon disease. In vitro, iPSC-CMs from these patients reproduced the histological features and autophagy failure of Danon disease. Administration of the DNA demethylating agent 5-aza-2’-deoxycytidine reactivated the silent
LAMP2
allele in iPSCs and iPSC-CMs in female patients with Danon disease and ameliorated their autophagy failure, supporting the application of a patient-specific iPSC platform for disease modeling and drug screening.

Conclusions:
Our iPSC-CM platform provides novel mechanistic and therapeutic insights into the contribution of random X chromosome inactivation to disease phenotype in X-linked Danon disease.
Genetic and Pharmacologic Inhibition of the Chemokine Receptor CXCR2 Prevents Experimental Hypertension and Vascular Dysfunction
Authors: Wang Lei , Zhao Xue-Chen , Cui Wei , Ma Yong-Qiang , Ren Hua-Liang , Zhou Xin , Fassett John , Yang Yan-Zong , Chen Yingjie , Xia Yun-Long , Du Jie , Li Hui-Hua 
Published: September 2016

Background:
The recruitment of leukocytes to the vascular wall is a key step in hypertension development. Chemokine receptor CXCR2 mediates inflammatory cell chemotaxis in several diseases. However, the role of CXCR2 in hypertension development and the underlying mechanisms remain unknown.

Methods:

Angiotensin II (490 ng·kg
-1
·min
-1
) or deoxycorticosterone acetate (DOCA) salt–induced mouse hypertensive models in genetic ablation, pharmacologic inhibition of CXCR2, and adoptive bone marrow transfer mice were used to determine the role of CXCR2 in hypertension (measured by radiotelemetry and tail-cuff system), inflammation (verified by flow cytometry and quantitative real-time polymerase chain reaction [PCR] analysis), vascular remodeling (studied by haematoxylin and eosin and Masson’s trichrome staining), vascular dysfunction (assessed by aortic ring), and oxidative stress (indicated by nicotinamide adenine dinucleotide phosphate [NADPH] oxidase activity, dihydroethidium staining, and quantitative real-time PCR analysis). Moreover, the blood CXCR2
+
cells in normotensive controls and hypertension patients were analyzed by flow cytometry.

Results:

Angiotensin II significantly upregulated the expression of CXCR2 mRNA and protein and increased the number of CD45
+
CXCR2
+
cells in mouse aorta (n=8 per group). Selective CXCR2 knockout (CXCR2
-/-
) or pharmacological inhibition of CXCR2 markedly reduced angiotensin II- or DOCA-salt-induced blood pressure elevation, aortic thickness and collagen deposition, accumulation of proinflammatory cells into the vascular wall, and expression of cytokines (n=8 per group). CXCR2 inhibition also ameliorated angiotensin II-induced vascular dysfunction and reduced vascular superoxide formation, NADPH activity, and expression of NADPH oxidase subunits (n=6 per group). Bone marrow reconstitution of wild-type mice with CXCR2
-/-
bone marrow cells also significantly abolished angiotensin II-induced responses (n=6 per group). It is important to note that CXCR2 blockade reversed established hypertension induced by angiotensin II or DOCA-salt challenge (n=10 per group). Furthermore, we demonstrated that CXCR2
+
proinflammatory cells were higher in hypertensive patients (n=30) compared with normotensive individuals (n=20).

Conclusions:

Infiltration of CXCR2
+
cells plays a pathogenic role in arterial hypertension and vascular dysfunction. Inhibition of CXCR2 pathway may represent a novel therapeutic approach to treat hypertension.
Derivation Lexicale En Iangues Gestveiles Et Chinoises
Authors: Shun-chiu Yau 
Published: October 2016

Given a certain number of basic signs (gestural lexical items), the lexicon of a sign language can expand by modifying the morphology of its basic items. The case I present here concerns only those data where morphological modification is exploited as a lexical branching device, i.e., where a sign acquires a new signification but no additional, morphemes after undergoing such a modification, and the root form of that sign retains its original, meaning.The movement parameter is the principal device of an intrinsic nature for lexical branching in sign languages. In this respect, the movement modification in sign language is comparable to tonal modification in certain oral languages. In Cantonese, for example, the difference between cognate pairs such as "sugar:sweet is marked by a tonal shift. Tones are generally attached to the vowels. Since vowels are the nuclei of syllables in a sonorous modality as movements are of signs in a visually dynamic medium, we can consider the two lexical, branching mechanisms in their respective systems to be parallel linguistic phenomena.
Les Onomatopees Et Meophones Dujaponais
Authors: Labrune Laurence 
Published: October 2016

Japanese imitative words (gitaigo and giongo) are not simple attempts to reproduce extra-Linguistical phenomena in a non arbitrary way.The majority of these words results from definite phonological and suffixal rules operating on a few root words and constitute many semantico-formal families. This shows that Japanese imitative words are grammaticalized and that their creation is subjected to rules.The second interesting point concerning these words is that many of them are formally very close to Corean imitative words. Such a resemblance attests the fact that Japanese onomatopoeia and ideophones constitute the substratum of a Language which was once common to the Japanese and Korean peoples.
PLURALITE EN COREEN : DEUX FONCTIONS DE TUL
Authors: Prost Martine 
Published: October 2016

The aim of this article is to establish the existence, in the Korean language, of a marker of pluralization TUL, which acts either as a nominal suffix, or as a thematic particle.
The nominal suffix (NS) is the marker of an operation of local pluralization limited to the suffixed noun, whereas the thematic particle (TP) is that of an operation of global pluralization enlarged to the whole sentence.
The main characteristics of the NS are:
- its limitation in use to the case of undetermined plurality.
- its obligatory (and not optional as often stated) use in some contexts (with the deictics for example)
- its compatibility with animate nouns
The main characteristics of the TP are :
- its mobility, since it may be attached to nearly any element in the sentence.
- its commun distributionwith the other Korean thematic particles
- more than strictly grammatical enunciative function.
Tropical Cyclone Center Positions from Sequences of HDSS Sondes Deployed along High-Altitude Overpasses
Authors: Creasey Robert L. , Elsberry Russell L. 
Published: September 2016

Abstract
A method is developed to calculate the zero-wind center (ZWC) position from a sequence of Yankee High Density Sounding System (HDSS) dropwindsondes deployed during a high-altitude overpass of a tropical cyclone. The approach is similar to the Willoughby and Chelmow technique in that it utilizes the intersections of bearings normal to the wind directions across the center to locate the ZWC position. Average wind directions over 1-km layers are calculated from the accurate global positioning system (GPS) latitude–longitude positions as the HDSS sonde falls from the 60 000-ft flight level of the NASA WB-57 to the ocean surface. An iterative procedure is used to also account for the storm translation, which is necessary to put these high-frequency HDSS observations into a storm-relative coordinate system. The Tropical Cyclone Intensity (TCI-15) mission into Hurricane Joaquin on 4 October 2015 is examined here. The ZWC positions from two center overpasses indicate the vortex tilts from 1- to 10-km elevation and rotates cyclonically with height.
Performance Assessment for Mastoidectomy: State of the Art Review
Authors: Sethia Rishabh , Kerwin Thomas F. , Wiet Gregory J. 
Published: September 2016

ObjectiveThe aim of this report is to provide a review of the current literature for assessment of performance for mastoidectomy, to identify the current assessment tools available in the literature, and to summarize the evidence for their validity.Data SourcesThe MEDLINE database was accessed via PubMed.Review MethodsInclusion criteria consisted of English‐language published articles that reported use of a mastoidectomy performance assessment tool. Studies ranged from 2007 to November 2015 and were divided into 2 groups: intraoperative assessments and those performed with simulation (cadaveric laboratory or virtual reality). Studies that contained specific reliability analyses were also highlighted. For each publication, validity evidence data were analyzed and interpreted according to conceptual definitions provided in a recent systematic review on the modern framework of validity evidence.ConclusionsTwenty‐three studies were identified that met our inclusion criteria for review, including 4 intraoperative objective assessment studies, 5 cadaveric studies, 10 virtual reality simulation studies, and 4 that used both cadaveric assessment and virtual reality.Implications for PracticeA review of the literature revealed a wide variety of mastoidectomy assessment tools and varying levels of reliability and validity evidence. The assessment tool developed at Johns Hopkins possesses the most validity evidence of those reviewed. However, a number of agreed‐on specific metrics could be integrated into a standardized assessment instrument to be used nationally. A universally agreed‐on assessment tool will provide a means for developing standardized benchmarks for performing mastoid surgery.
Effect of Preoperative Counseling on Hospital Length of Stay and Readmissions after Total Laryngectomy
Authors: Shenson Jared A. , Craig Jennifer N. , Rohde Sarah L. 
Published: September 2016

ObjectiveTotal laryngectomy (TL) is a high‐cost procedure with patients at risk for significant postoperative health care use. Face‐to‐face preoperative counseling provided by speech‐language pathologists is a relatively inexpensive intervention that may improve care quality and decrease costs. We evaluated if preoperative counseling for patients undergoing TL was associated with differences in length of stay (LOS), use of the emergency department (ED), or unplanned readmissions within 30 days of discharge. A secondary analysis identified predictors of these 3 outcomes.Study DesignCase series with chart review.SettingAcademic medical center in the United States.Subjects and MethodsPatients were included if they underwent TL from 2011 to 2015. Patient demographics and comorbidities, surgical characteristics, and perioperative care data were retrieved and analyzed for 116 patients. Univariate and multivariate models were constructed for 3 outcomes.ResultsLOS was significantly lower for patients receiving counseling (–3.0 days, P =. 02). No differences were observed in rates of 30‐day ED visits or unplanned readmissions. Care provided by high‐volume surgeons was associated with decreased LOS (P =. 005), while having postoperative complications increased LOS (P <. 001). High rates of ED visits (12.1%) and readmissions (20.6%) were observed. Discharge to inpatient rehabilitation and the patient’s home distance from the institution were predictors of ED visits. TL as salvage therapy and occurrence of postoperative complications were risk factors for readmission.ConclusionPreoperative counseling was associated with marked reduction in LOS following TL without increased readmissions, which suggests that it may promote safe, earlier patient readiness for discharge.