bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deubiquitinating Enzyme USP9X Suppresses Tumor Growth via LATS Kinase and Core Components of the Hippo Pathway
Authors: Toloczko Aleksandra , Guo Fusheng , Yuen Hiu-Fung , Wen Qing , Wood Stephen A. , Ong Yan Shan , Chan Pei Yi , Shaik Asfa Alli , Gunaratne Jayantha , Dunne Mark J. , Hong Wanjin , Chan Siew Wee 
Published: July 2017

Abstract
The core LATS kinases of the Hippo tumor suppressor pathway phosphorylate and inhibit the downstream transcriptional co-activators YAP and TAZ, which are implicated in various cancers. Recent studies have identified various E3 ubiquitin ligases that negatively regulate the Hippo pathway via ubiquitination, yet few deubiquitinating enzymes (DUB) have been implicated. In this study, we report the DUB USP9X is an important regulator of the core kinases of this pathway. USP9X interacted strongly with LATS kinase and to a lesser extent with WW45, KIBRA, and Angiomotin, and LATS co-migrated exclusively with USP9X during gel filtration chromatography analysis. Knockdown of USP9X significantly downregulated and destabilized LATS and resulted in enhanced nuclear translocation of YAP and TAZ, accompanied with activation of their target genes. In the absence of USP9X, cells exhibited an epithelial-to-mesenchymal transition phenotype, acquired anchorage-independent growth in soft agar, and led to enlarged, disorganized, three-dimensional acini. YAP/TAZ target gene activation in response to USP9X knockdown was suppressed by knockdown of YAP, TAZ, and TEAD2. Deletion of USP9X in mouse embryonic fibroblasts resulted in significant downregulation of LATS. Furthermore, USP9X protein expression correlated positively with LATS but negatively with YAP/TAZ in pancreatic cancer tissues as well as pancreatic and breast cancer cell lines. Overall, these results strongly indicate that USP9X potentiates LATS kinase to suppress tumor growth. Cancer Res; 77(18); 4921–33. ©2017 AACR.
MUC1-Mediated Metabolic Alterations Regulate Response to Radiotherapy in Pancreatic Cancer
Authors: Gunda Venugopal , Souchek Joshua , Abrego Jaime , Shukla Surendra K. , Goode Gennifer D. , Vernucci Enza , Dasgupta Aneesha , Chaika Nina V. , King Ryan J. , Li Sicong , Wang Shuo , Yu Fang , Bessho Tadayoshi , Lin Chi , Singh Pankaj K. 
Published: July 2017

Abstract
Purpose: MUC1, an oncogene overexpressed in multiple solid tumors, including pancreatic cancer, reduces overall survival and imparts resistance to radiation and chemotherapies. We previously identified that MUC1 facilitates growth-promoting metabolic alterations in pancreatic cancer cells. The present study investigates the role of MUC1-mediated metabolism in radiation resistance of pancreatic cancer by utilizing cell lines and in vivo models.
Experimental Design: We used MUC1-knockdown and -overexpressed cell line models for evaluating the role of MUC1-mediated metabolism in radiation resistance through in vitro cytotoxicity, clonogenicity, DNA damage response, and metabolomic evaluations. We also investigated whether inhibition of glycolysis could revert MUC1-mediated metabolic alterations and radiation resistance by using in vitro and in vivo models.
Results: MUC1 expression diminished radiation-induced cytotoxicity and DNA damage in pancreatic cancer cells by enhancing glycolysis, pentose phosphate pathway, and nucleotide biosynthesis. Such metabolic reprogramming resulted in high nucleotide pools and radiation resistance in in vitro models. Pretreatment with the glycolysis inhibitor 3-bromopyruvate abrogated MUC1-mediated radiation resistance both in vitro and in vivo, by reducing glucose flux into nucleotide biosynthetic pathways and enhancing DNA damage, which could again be reversed by pretreatment with nucleoside pools.
Conclusions: MUC1-mediated nucleotide metabolism plays a key role in facilitating radiation resistance in pancreatic cancer and targeted effectively through glycolytic inhibition. Clin Cancer Res; 23(19); 5881–91. ©2017 AACR.
Вплив поліморфізму генів PTHR1 та COL1A1 на розвиток захворювань тканин пародонта у людей молодого віку
Authors: Luchynskyi M. A. , Boliuk Y. V. , Luchynskyi V. M. 
Published: July 2017

At the present stage of development of dentistry, the leading Ukrainian and foreign scientists devote a considerable part of the research to a deeper study of the etiology and pathogenetic mechanisms of periodontal tissue diseases and the influence of various exogenous and endogenous factors on their course.The aim of the study – to learn the ability and methods of forecasting and early diagnosis of the periodontal tissue lesions in young people. Materials and Methods. During our research we examined 24 young people with periodontal tissue diseases, who were included to the main group, and 15 healthy people, who formed the control group. The complex clinical examination was performed in each research group. It was studied the distribution of polymorphous variants of the type I parathormone receptor and the α1-chain of collagen gene with a help of polymerase chain reaction by restrictase cleavage of DNA fragments and electrophoresis in polyacrylamide gel (AA/BA 29:1). Results and Discussion. The distribution of genotypes by PTHR1 gene in control group was similar to those in main group (p>0.05). Also we didn’t find the difference between frequencies of the separate alleles in people with periodontal tissue pathology and without it (p>0.05). Yes, the repetitions of the allele 5 encoding normal type I parathormone receptor were found more often, comparing with the allele 6 that is responsible for the formation of unfunctional PTHR1 (р<0.001) in both main and control groups. The dominance of the genotype TT, which corresponds to the pathology, was found in young people with the periodontal tissue lesions – (38.46 ± 4.79) %, while among the control group the genotype of norm GG was met the most often – (68.24±5.08) %. Also, the frequency of repetitions of the allele T encoding the imperfect collagen chain was (57.60±3.79) % in young people with periodontal diseases, and in the control group this figure was (13.27±2.81) %, p<0.001. Conclusions. According to our results the presence of allele T and genotype TT that correspond the imperfect collagen chain may be one of the causes of periodontal tissue pathology.
Effects of Non–Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: A Systematic Review and Meta‐Analysis
Authors: Pan Kuo‐Li , Singer Daniel E. , Ovbiagele Bruce , Wu Yi‐Ling , Ahmed Mohamed A. , Lee Meng 
Published: July 2017

Background

The original non–vitamin K antagonist oral anticoagulant (
NOAC
) trials in nonvalvular atrial fibrillation (
AF
) enrolled patients with native valve pathologies. The object of this study was to quantify the benefit–risk profiles of
NOAC
s versus warfarin in
AF
patients with native valvular heart disease (
VHD
).

Methods and Results

Trials were identified by exhaustive literature search. Trial data were combined using inverse variance weighting to produce a meta‐analytic summary hazard ratio (
HR
) and 95% confidence interval (
CI
) of efficacy and safety of
NOAC
s versus warfarin. Our final analysis included 4 randomized controlled trials that enrolled 71 526 participants, including 13 574 with
VHD
. Pooling results from included trials showed that
NOAC
s versus warfarin reduced stroke or systemic embolism (
HR
: 0.70; 95%
CI
, 0.60–0.82) and intracranial hemorrhage (
HR
: 0.47; 95%
CI
, 0.24–0.92) in
AF
patients with
VHD
. However, risk reduction of major bleeding and intracranial hemorrhage was driven by apixaban, edoxaban, and dabigatran (HR for major bleeding: 0.79 [95%
CI
, 0.69–0.91]; HR for intracranial hemorrhage: 0.33 [95%
CI
, 0.25–0.45]) but not rivaroxaban (HR for major bleeding: 1.56 [95%
CI
, 1.20–2.04]; HR for intracranial hemorrhage: 1.27 [95%
CI
, 0.77–2.10]).

Conclusions

Among patients with
AF
and native
VHD
,
NOAC
s reduce stroke and systemic embolism compared with warfarin. Evidence shows that apixaban, dabigatran, and edoxaban also reduce bleeding in this patient subgroup, whereas major bleeding (but not intracranial hemorrhage or mortality rate) is significantly increased in
VHD
patients treated with rivaroxaban.
NOAC
s are a reasonable alternative to warfarin in
AF
patients with
VHD
.
Microclimate Variation among Urban Land Covers: The Importance of Vertical and Horizontal Structure in Air and Land Surface Temperature Relationships
Authors: Crum Steven M. , Jenerette G. Darrel 
Published: July 2017

AbstractAir and land surface warming effects from urbanization are of increasing concern because of expanding heat-related impacts on human health. Many studies have investigated land-cover effects on air temperature Ta or land surface temperature (LST) individually, but relatively few studies have examined the relationships between these two heat indicators and other meteorological variables. The authors investigate how land cover influences local distributions of LST, Ta, and relative humidity (RH) and their interactions. During July 2016, 30 Ta and RH sensors were deployed at two heights above the ground (0.1 and 1.5 m) along with a thermal camera and an anemometer to quantify the influence of surface dynamics on atmospheric micrometeorological conditions. Sensors were distributed in Riverside, California, over five common urban land covers: asphalt, bare surface, turf grass, short trees, and tall trees. Stronger Ta–LST relationships were observed at 0.1 m for asphalt, bare surface, and grass and at 1.5 m for short and tall trees. Excluding grass, greater Ta–LST differences were found for daytime than for nighttime. To add to the complexity of Ta–LST relationships, increasing spatial variation in LST during the day for short- and tall-tree land covers were found. Furthermore, both wind velocity and LST were correlated with Ta vertical distributions. Higher RH and lower LST, Ta, and vapor pressure deficit were found in vegetated covers. Through the use of thermal imagery and meteorological measures, it was found that distinct land-cover influences on microclimate exist and that estimates of urban Ta using LST may improve with the use of land-cover-specific relationships.
Performance of the New NCEP Global Ensemble Forecast System in a Parallel Experiment
Authors: Zhou Xiaqiong , Zhu Yuejian , Hou Dingchen , Luo Yan , Peng Jiayi , Wobus Richard 
Published: July 2017

Abstract
A new version of the Global Ensemble Forecast System (GEFS, v11) is tested and compared with the operational version (v10) in a 2-yr parallel run. The breeding-based scheme with ensemble transformation and rescaling (ETR) used in the operational GEFS is replaced by the ensemble Kalman filter (EnKF) to generate initial ensemble perturbations. The global medium-range forecast model and the Global Forecast System (GFS) analysis used as the initial conditions are upgraded to the GFS 2015 implementation version. The horizontal resolution of GEFS increases from Eulerian T254 (~52 km) for the first 8 days of the forecast and T190 (~70 km) for the second 8 days to semi-Lagrangian T574 (~34 km) and T382 (~52 km), respectively. The sigma pressure hybrid vertical layers increase from 42 to 64 levels. The verification of geopotential height, temperature, and wind fields at selected levels shows that the new GEFS significantly outperforms the operational GEFS up to days 8–10 except for an increased warm bias over land in the extratropics. It is also found that the parallel system has better reliability in the short-range probability forecasts of precipitation during warm seasons, but no clear improvement in cold seasons. There is a significant degradation of TC track forecasts at days 6–7 during the 2012–14 TC seasons over the Atlantic and eastern Pacific. This degradation is most likely a sampling issue from a low number of TCs during these three TC seasons. The results for an extended verification period (2011–14) and the recent two hurricane seasons (2015 and 2016) are generally positive. The new GEFS became operational at NCEP on 2 December 2015.
Assessing Markers of Working Memory Function in Dissociative Identity Disorder Using Neutral Stimuli: A Comparison with Clinical and General Population Samples
Authors: Dorahy Martin J. , Irwin Harvey J. , Middleton Warwick 
Published: July 2017

Objectives: Memory functioning is a central conceptual and phenomenological aspect of dissociative identity disorder (DID). Most empirical work on memory functions in DID has focused on retrieval deficits either within or between dissociated identities. The current study attempted to remedy the scant attention given to working memory functioning. Method: In samples representing the DID, non-clinical, depressed, posttraumatic stress disorder (PTSD) and psychosis populations (n = 10 per group), neutral stimuli were used to examine three markers of working memory functioning: one measuring inhibition; one assessing facilitation; and one measuring interference. Results: With the exception of the psychosis sample all groups displayed significant negative priming in the distractor inhibition condition. Facilitation effects were demonstrated by the DID and PTSD groups only. Interference effects were evident in all samples, though the DID and non-clinical groups demonstrated significantly more interference than the psychosis cohort. Distractor inhibition was related to overall schizotypy scores, and dissociation was related to scores in the facilitation condition. Conclusions: The DID sample displayed a completely distinct functional working memory profile to the psychosis sample when assessed with emotionally neutral stimuli. However, the working memory profile in the DID sample was not entirely dissimilar to the other comparison groups.
Race and the Criminal Process: Breaking the Mould to Ensure Accurate Ethnic Monitoring
Authors: Sharma Kamal 
Published: July 2017

The media, judiciary, legislature and the Executive currently agree that the criminal process is in need of reform. Indeed, on Tuesday 18 June 2002, Tony Blair described the criminal justice system as ‘antique and ineffectual’. This article investigates the purposes and uses of racial and ethnical terminologies in the criminal justice system. Notwithstanding the importance of existing racial definitions in criminal justice, a standard definition of ethnicity is regarded as necessary to ensure that ethnic monitoring is accurate and effective. Therefore this article questions the validity, accuracy and purposes of the terminologies used in contemporary and past studies in relation to the most extensive reports on ethnic monitoring; namely the National Censuses of Population, the Home Office Research Statistics and Development Directorate's publications and the British Crime Surveys'. This article also considers the impact that foreseeable social and demographic changes may have on the use of racial and ethnic classifications in the criminal justice system, as well as the ways in which the various bodies of the criminal process may prepare for potential changes.
Fraud—The Latest Law Commission Proposals
Authors: Sullivan G. R. 
Published: July 2017

This article examines the latest Law Commission proposals for replacing conspiracy to defraud with statutory offences. The Report proposes a general offence of fraud which can be committed three ways: (1) by false representation; (2) wrongfully failing to disclose; (3) abuse of position. The first form of the general offence constitutes a very useful reform whereas aspects of the second and third ways of committing the general offence are criticised for engendering uncertainty and for their potential to criminalise otherwise valid civil law transactions. Additionally the Report proposes a broad offence of obtaining services by dishonesty; this is found to be a very useful proposal.
Flow Rates of Resting Whole and Stimulated Parotid Saliva in Relation to Age and Gender
Authors: Percival R.S. , Challacombe SJ , Marsh P.D. 
Published: July 2017

Dry mouth is a common feature in the elderly, but it is not clear what proportion of incidences are related to functional disturbances and whether age per se and gender play a role. The aim of this study was to determine the effects of age and gender on salivary flow rates. The effect of age on unstimulated (resting) whole and stimulated parotid saliva flow rates was determined in 116 unmedicated, healthy individuals. The subjects were divided into four age groups: 20-39 years (group A), 40-59 years (group B), 60-79 years (group C), and 80 years and over (group D). A significant decrease in the secretion rates of unstimulated whole saliva in relation to age was observed in the study population (p < 0.001). However, the flow rates of stimulated parotid saliva were not significantly different in the four age groups. Females had significantly lower mean flow rates than males for both unstimulated (resting) whole saliva (p < 0.005) and stimulated parotid saliva (p < 0.05). In the study as a whole, significant negative correlations were found between either the DMF index (decayed, missing, and filled teeth) or the DMFS index (decayed, missing, and filled tooth surfaces) and the flow rates of unstimulated whole saliva (p < 0.02), but no relationship to stimulated parotid saliva flow rates was apparent. The results suggest that elderly subjects have no impairment in their ability to respond to sialogogues but that resting saliva rates are significantly lower than in younger individuals and may contribute to the increase in oral mucosal diseases seen in the elderly.
Distribution of Protein Kinase Ca and Accumulation of Extracellular Ca2+ During Early Dentin and Enamel Formation
Authors: Bawden J.W. , Rozell B. , Wurtz T. , Fouda N. , Hammarstrom L. 
Published: July 2017

Activation of the protein kinase C (PKC)-related signal transduction system has been associated with phenotypic expression in a wide variety of cell types. In in vitro studies, it has often been activated by relatively small increases in the Ca2+ concentration ([Ca2+]) in the medium. The studies reported here explored the hypothesis that localized increases in the extracellular [Ca2+] and activation of the PKC-related pathway may be involved in early dentin and enamel formation. Whole-head, freeze-dried sections through the developing molars of 5-day-old rats were evaluated by methods that localized non-crystalline Ca2+. Immunohistochemical methods were adapted for use with the freeze-dried sections, and two monoclonal antibodies were used to localize PKCa in the formative cells of the developing teeth. Low concentrations of extracellular Ca2+ were observed in the early, unmineralized dentin in the area of ameloblast differentiation. Increased concentrations occurred at the point of initial dentin mineralization, immediately before the beginning of enamel matrix deposition. PKCa was localized in the differentiating odontoblasts, at the beginning of dentin matrix deposition. It was intensely localized in the distal borders of the pre-ameloblasts, and appeared to redistribute in the cells during ameloblast differentiation. These observations suggest that local increases in the extracellular [Ca2+] and the PKC signal transduction pathway may be involved in key inductions in the early stages of dentin and enamel formation.
Indentation Cracking of Composite Matrix Materials
Authors: Baran G. , Shin W. , Abbas A. , Wunder S. 
Published: July 2017

Composite restorative materials wear by a fatigue mechanism in the occlusal contact area. Here, tooth cusps and food debris cyclically indent the restoration. Modeling this phenomenon requires an understanding of material response to indentation. The question in this study was whether material response depends on indenter size and geometry, and also, whether polymers used in restorative materials should be considered elastic and brittle, or plastic and ductile for modeling purposes. Three resins used as matrices in proprietary restorative composites were the experimental materials. To ascertain the influence of glass transition temperature, liquid sorption, and small amounts of filler on indentation response, we prepared materials with various degrees of cure; some samples were soaked in a 50/50 water/ethanol solution, and 3 vol% silica was added in some cases. Indentation experiments revealed that no cracking occurred in any material after indentation by Vickers pyramid or spherical indenters with diameters equal to or smaller than 0.254 mm. Larger spherical indenters induced subsurface median and surface radial and/or ring cracks. Critical loads causing subsurface cracks were measured. Indentation with suitably large spherical indenters provoked an elastoplastic response in polymers, and degree of cure and Tg had less influence on critical load than soaking in solution. Crack morphology was correlated with yield strain. Commonly held assumptions regarding the brittle elastic behavior of composite matrix materials may be incorrect.
Insights into how to conduct a clinical trial in the UK
Authors: Abozguia Khalid , Phan Thanh Trung , Shivu Ganesh Nallur , Maher Abdul , Ahmed Ibrar , Frenneaux Michael P 
Published: July 2017

Summary New researchers may find starting and conducting clinical studies in the UK complicated and time-consuming. In this article, we describe our collective experiences and provide some pointers on how to navigate through the various committees and regulatory bodies. The article is intended to aid junior researchers in understanding the study process and to provide them with some insight on how to get through this complex system successfully.
The Neoclassical Consumer: are they Real or Just Fata Morgana?
Authors: Amir Shmuel 
Published: July 2017

A basic assumption of neoclassical macroeconomic theory is that in a market economy, consumers choose bundles of goods to maximize their budget-constrained utilities. A direct conclusion of this assumption is that in picking up their optimal bundles, consumers set their marginal utilities in proportion to the market prices of the goods consumed. In this paper, we show this type of behavior to contradict any behavioral pattern that is consistent with the second law of thermodynamics. This makes the “neoclassical consumer” the only system so far known to be able to evade the governance of this law. Should real consumers behave in agreement with the second law, their demands cannot satisfy the proportionality condition, and their marginal utilities cannot be determined solely by the prices. Since no real system has been found to violate the second law, and it is unlikely that one will ever be found, the need to revise consumer theory is there, even if empirically it has not yet been tested and refuted. JEL Classification: B41, D11
Designing Ecolabels In Order To Mitigate Market Failures
Authors: Bougherara Douadia , Grolleau Gilles 
Published: July 2017

For the market for ecofriendly characteristics of agrofood products to function effectively, means of mitigating asymmetric information, informational overload and public goods properties are necessary. Ecolabel success requires a design and an implementation capable of mitigating simultaneously these three sources of market failures. Our contribution differs from many to date by (1) introducing and analyzing the informational overload as a source of market failure and (2) considering the ecolabel, not only as a tool to re-establish information symmetry between the producer and consumer but also as a way to overcome informational overload and public goods problems. We analyze how these sources of market failures may be mitigated by providing information perceived as trustworthy, tying credence and public attributes to verifiable and private attributes and designing the ecolabel as a cognitive support for consumers. We provide an exploratory qualitative study of several French ecolabels to stress how they more or less succeed in attenuating the identified sources of market failures. Several implications for policymakers and managers are stressed. We conclude by suggesting several issues requiring further investigations. JEL Classification Numbers: D11, D21, L15