bluuebunny/crossref_metadata_2025 huggingface dataset:
Circuit Complexity, Proof Complexity, and Polynomial Identity Testing
Authors: Grochow Joshua A. , Pitassi Toniann
Published: November 2018

We introduce a new and natural algebraic proof system, whose complexity measure is essentially the algebraic circuit size of Nullstellensatz certificates. This enables us to exhibit close connections between effective Nullstellensatzë, proof complexity, and (algebraic) circuit complexity. In particular, we show that any super-polynomial lower bound on any Boolean tautology in our proof system implies that the permanent does not have polynomial-size algebraic circuits (VNP ≠ VP). We also show that super-polynomial lower bounds on the number of lines in Polynomial Calculus proofs imply the Permanent versus Determinant Conjecture. Note that there was no proof system prior to ours for which lower bounds on an arbitrary tautology implied
any
complexity class lower bound.

Our proof system helps clarify the relationships between previous algebraic proof systems. In doing so, we highlight the importance of polynomial identity testing (PIT) in proof complexity. In particular, we use PIT to illuminate AC
0
[
p
]-Frege lower bounds, which have been open for nearly 30 years, with no satisfactory explanation as to their apparent difficulty.

Finally, we explain the obstacles that must be overcome in any attempt to extend techniques from algebraic circuit complexity to prove lower bounds in proof complexity. Using the algebraic structure of our proof system, we propose a novel route to such lower bounds. Although such lower bounds remain elusive, this proposal should be contrasted with the difficulty of extending AC
0
[
p
] circuit lower bounds to AC
0
[
p
]-Frege lower bounds.
Maintenance of Smart Buildings using Fault Trees
Authors: Cauchi Nathalie , Hoque Khaza Anuarul , Stoelinga Marielle , Abate Alessandro
Published: November 2018

Timely maintenance is an important means of increasing system dependability and life span. Fault Maintenance trees (FMTs) are an innovative framework incorporating both maintenance strategies and degradation models and serve as a good planning platform for balancing total costs (operational and maintenance) with dependability of a system. In this work, we apply the FMT formalism to a Smart Building application and propose a framework that efficiently encodes the FMT into Continuous Time Markov Chains. This allows us to obtain system dependability metrics such as system reliability and mean time to failure, as well as costs of maintenance and failures over time, for different maintenance policies. We illustrate the pertinence of our approach by evaluating various dependability metrics and maintenance strategies of a Heating, Ventilation, and Air-Conditioning system.
1
Designing Green Communication Systems for Smart and Connected Communities via Dynamic Spectrum Access
Authors: Shah Vijay K. , Bhattacharjee Shameek , Silvestri Simone , Das Sajal K.
Published: November 2018

Smart and connected communities (SCCs) are emerging as a novel paradigm that allows the community residents to be connected with surrounding environments through smart technologies. However, there remain important challenges to fully exploit the potential of SCCs in improving societal well-being and prosperity. In particular, there is a need for designing
green
communication systems that are also capable of providing high
quality of service
(QoS) to distribute and collect information to and from SCCs. However, simultaneously satisfying both of these criteria is difficult due to varying demands posed by heterogeneous sensing modalities, lack of dedicated infrastructure in rural/sub-urban areas, and certain sustainability constraints. While low-power short-range technologies often fail to achieve high QoS, using 3G or 4G technologies (LTE, LTE-A, GSM) for SCCs will eventually face spectrum scarcity and cross technology interference. In recent times,
Dynamic spectrum access
(DSA) has been proposed as a solution to overcome policy constraints and improve spectrum scarcity by spectrum sharing. In this article, we show that harnessing DSA in the context of SCCs can also achieve notable benefits in terms of energy efficiency and sustainability. Specifically, we propose a novel architecture for designing sustainable SCCs using a small-scale DSA-enabled overlay network that improves end-to-end energy efficiency of the network while guaranteeing QoS. We also propose a dynamic spectrum band selection approach that intelligently matches any message requirement to a suitable band type by exploiting distinct electro-magnetic characteristics of various bands. Since data generated in SCCs are typically valuable only when delivered within a certain
hard
(or
soft
) deadline, we formulate a linear optimization problem for determining the most energy-efficient path that ensures a delivery time within the hard deadline. After proving that such a problem is NP-Hard, we propose an exact pseudo-polynomial time dynamic programming algorithm to solve it followed by a polynomial time greedy heuristic. Additionally, we formulate a non-linear optimization problem to find the optimal path when the message delivery time is defined as a
soft
deadline and extend our greedy heuristic to handle soft deadlines. Compared to the homogeneous band access approaches that opportunistically access free channels within a given spectrum band, our extensive simulation study shows that the proposed dynamic multi-band selection approach significantly improves the achievable energy efficiency while meeting various hard and soft deadlines.
Adhesion and Proliferation of Osteoblast-Like Cells on Porous Polyetherimide Scaffolds
Authors: Zhang Yanbo , Li Ruiyan , Wu Wenzheng , Qing Yun’an , Tang Xiongfeng , Ye Wenli , Zhang Zhiyong , Qin Yanguo
Published: November 2018

The purpose of this work was to investigate the porous polyetherimide scaffold (P-PEIs) as an alternative biopolymer for bone tissue engineering. The P-PEIs was fabricated via solvent casting and particulate leaching technique. The morphology, phase composition, roughness, hydrophilicity, and biocompatibility of P-PEIs were evaluated and compared with polyetherimide (PEI) and Ti6Al4V disks. P-PEIs showed a biomimetic porous structure with a modulus of 78.95 ± 2.30 MPa. The water contact angle of P-PEIs was 75.4 ± 3.39°, which suggested that P-PEIs had a wettability surface. Moreover, P-PEIs provides a feasible environment for cell adhesion and proliferation. The relative cell adhesion capability and the cell morphology on P-PEIs were better than PEI and Ti6Al4V samples. Furthermore, the MC3T3-E1 cells on P-PEIs showed faster proliferation rate than other groups. It was revealed that the P-PEIs could be a potential material for the application of bone regeneration.
Effect of Nanoadditives on Bitumen Aging Resistance: A Critical Review
Authors: Filippi Sara , Cappello Miriam , Merce Manuel , Polacco Giovanni
Published: November 2018

Starting from the eighties, the use of nanoadditives registered an increasing attention in the scientific and patent literature, especially for the case of polymeric nanocomposites. In the last decade, this involved bituminous materials, modified either with nanosized fillers or with polymeric nanocomposites. One of the expected benefits is an increased resistance of the binder to aging. After a short introduction underlining the uncertainties and risks of artefacts in aging tests, a review is given, focusing on the antiaging properties of layered silicates, which are by far the most important nanoadditives for bitumens. Together with layered silicates, other materials such as nanohydrated lime, nanosilica, and layered double hydroxides are mentioned. Preparation and characterization of the binary bitumen/layered silicate and ternary bitumen/layered silicate/polymer systems are described in order to individuate the aspects that influence the antiaging effect. Even if the available literature is quite abundant and unanimously confirms that nanoadditives may improve bitumen durability, there is a lack of studies clarifying the involved mechanisms. As it is for conventional fillers, it seems to be a combination of physical and chemical interactions. Nanoadditives with different chemistries, porosities, and interlayer spacings differently absorb the polar components from the bitumen, thus affecting their predisposition to oxidative aging.
Exploration of Mechanisms of Joint Deterioration in Concrete Pavements regarding Interfacial Transition Zone
Authors: Wang Xin , Zhang Jiake , Wang Xuhao , Taylor Peter , Wang Kejin , Sun Xinjian
Published: November 2018

As a common issue for cold weather regions, premature deterioration of concrete at joints has been reported in many states. In this paper, the mechanisms of joint deterioration were investigated, and then, experimental investigations were conducted to further verify some of the mechanisms. It was found that freeze‐thaw (F‐T) damage and salt crystallization are not enough to cause the observed deterioration, but the deterioration near the interfacial transition zone (ITZ) may be the cause of some of the observed phenomena. In the experimental work, samples were tested at 40°F in salt solutions to observe the deterioration in the ITZ using the scanning electron microscope (SEM). Concrete tested in MgCl2 solution indicated distress in ITZ under SEM. It was found that ITZ may act as a shortcut for ion transfer to surrounding concrete near the joints and may also be the weak point for cracking due to expansion of the paste.
Enzymatic Extraction, Purification, and Characterization of Polysaccharides fromPenthorum chinense Pursh: Natural Antioxidant and Anti-Inflammatory
Authors: Lin Li-mei , Zhao Ling-jia , Deng Jing , Xiong Su-hui , Tang Jie , Li Ya-mei , Xia Bo-hou , Liao Duan-fang
Published: November 2018

Penthorum chinense Pursh(PCP) is a kind of functional food or medicine for liver protection. In the present work, Plackett-Burman design, steepest ascent method, and response surface methodology (RSM) were employed to obtain maximum total sugar yield. The experimental yield of 6.91% indicated a close agreement with the predicted yield of 7.00% of the model under optimized conditions. The major polysaccharide fraction (PCPP-1a) from PCPP was purified and identified as acidic polysaccharides with a high content of uronic acid (FT-IR, UV, HPGPC). PCPP had similar monosaccharide profile with PCPP-1a but was rich in galacturonic acid (HPLC). Both of PCPP and PCPP-1a possessed strong hydroxyl radical scavenging, DPPH radical scavenging, and Fe2+chelating activities. Moreover, they were revealed to show strong anti-inflammatory activities by inhibiting NO, TNF-α, and IL-1βrelease compared to LPS treatment in RAW264.7 cells. These data suggest that the polysaccharides from PCP could be potential natural products for treating ROS and inflammatory-related diseases.
Nonlinear Classical Elasticity Model for Materials with Fluid and Matrix Phases
Authors: Muñoz Rafael , Melchor Juan
Published: November 2018

Materials with fluid and matrix phases present different acoustic responses in each phase. While longitudinal waves propagate in both phases, shear waves do it only through the solid matrix. Longitudinal waves are mainly described by volumetric propagation and shear waves by deviatoric processes. In the case of nonlinear propagation cross effects occur between both components. This paper presents a new classical nonlinear model proposing a constitutive equation that separates volumetric and deviatoric effects. Four nonlinear constants of third order are defined. The formulation is compared to constitutive equations with Landau constants for weakly elasticity and both types of nonlinear constants related. Some reinterpretation of the Landau’s constants arises in terms of parallel or cross nonlinear effects between volumetric and deviatoric components.
Evaluation of Changes in Cariogenic Bacteria in a Young Moroccan Population with Fixed Orthodontic Appliances
Authors: Marda A. , Elhamzaoui S. , El Mansari A. , Souly K. , Farissi F. , Zouhdi M. , Zaoui F. , Bahije L.
Published: November 2018

Fixed orthodontic appliances hinder the maintenance of proper oral hygiene and result in dental plaque accumulation. Many studies report that qualitative changes in the dental flora occur after initiating the orthodontic treatment, but there is a paucity of literature on the same topic among Moroccan orthodontic patients. The aim of this study was to evaluate the changes of the oral microbial flora during the orthodontic treatment period of a young Moroccan population. Materials and Methods. Dental plaque samples of 18 patients, who were randomly selected before the placement of orthodontic appliances, were collected to isolate and identify the bacterial species involved using classical bacteriological methods for species’ culture and identification. The reading was recorded at T0 before placement of the device. New samples were taken again one month later and then three months afterwards, where the readings were recorded as T1 and T2, respectively. The culture was made via Columbia Agar with 5% sheep blood, Todd Hewitt Broth, and Schaedler medium containing vitamin K3. Bacterial species were identified using API-20 Strep for Streptococci and API-20 A for anaerobic bacteria. The phoenix system was used for identification. Results. After three months of orthodontic treatment, the increase in the frequency of Streptococcus sobrinus and Streptococcus mitis were significant (0.01 and 0.02, respectively) as well as for Lactobacillus (0.03). No significant difference was recorded for other bacterial species. Conclusion. There is a significant qualitative change in oral microorganisms after three months of orthodontic treatment, especially for bacteria that are incriminated in caries formation.
VTOL UAV Transition Maneuver Using Incremental Nonlinear Dynamic Inversion
Authors: Liu Zhenchang , Guo Jie , Li Mengting , Tang Shengjing , Wang Xiao
Published: November 2018

The paper seeks to study the control system design of a novel unmanned aerial vehicle (UAV). The UAV is capable of vertical takeoff and landing (VTOL), transition flight and cruising via the technique of direct force control. The incremental nonlinear dynamic inversion (INDI) approach is adopted for the 6-DOF nonlinear and nonaffine control of the UAV. Based on the INDI control law, a method of two-layer cascaded optimal control allocation is proposed to handle the redundant and coupled control variables. For the weight selection in optimal control allocation, a dynamic weight strategy is proposed. This strategy can adjust the weight of the objective function according to the flight states and mission requirements, thus determining the optimizing direction and ensuring the rationality of the allocation results. Simulation results indicate that the UAV can track the target trajectory accurately and exhibit continuous maneuverability in transition flight.
Determining the Margin of Safety for Damaging the Sphenoid Sinus with Nasal Septum Osteotome during Le Fort I Surgery in Young Adults
Authors: Saruhan Nesrin , Ataol Mert , Temiz Mustafa
Published: November 2018

Nasal septum (Obwegeser) osteotome is a basic instrument used for separating the nasal septum and maxilla during Le Fort I osteotomy. If this instrument is placed too high or tilted into the nasal cavity, sphenoid sinus and various adjacent vital structures may be damaged and serious bleeding, neurological complications, or blindness or even death may occur. The aim of this study is to determine the margin of safety for damaging the sphenoid sinus and the adjacent structures with nasal septum osteotome in the young adults: 49 male and 51 female patients between 15 and 25 ages who required a Cone Beam Computed Tomography (CBCT) examination as part of their routine examination. In the study sample consisting of CBCT images, the aimed surgical line, the line between spina nasalis anterior and vomer and the base of sphenoid sinus (undesired line), and tilt angle between surgical and undesirable lines were measured. As the primary outcome of this study, margin of safety for damaging the sphenoid sinus and adjacent vital structures with nasal septum osteotome during Le Fort surgeries in young adults recommended as 5 mm and 120. For this reason the importance of planning with preoperative CBCT before Le Fort I osteotomies has been revealed.
Object Detection in Ground-Penetrating Radar Images Using a Deep Convolutional Neural Network and Image Set Preparation by Migration
Authors: Ishitsuka Kazuya , Iso Shinichiro , Onishi Kyosuke , Matsuoka Toshifumi
Published: November 2018

Ground-penetrating radar allows the acquisition of many images for investigation of the pavement interior and shallow geological structures. Accordingly, an efficient methodology of detecting objects, such as pipes, reinforcing steel bars, and internal voids, in ground-penetrating radar images is an emerging technology. In this paper, we propose using a deep convolutional neural network to detect characteristic hyperbolic signatures from embedded objects. As a first step, we developed a migration-based method to collect many training data and created 53510 categorized images. We then examined the accuracy of the deep convolutional neural network in detecting the signatures. The accuracy of the classification was 0.945 (94.5%)–0.979 (97.9%) when using several thousands of training images and was much better than the accuracy of the conventional neural network approach. Our results demonstrate the effectiveness of the deep convolutional neural network in detecting characteristic events in ground-penetrating radar images.
The Detroit Research on Cancer Survivors (ROCS) Pilot Study: A Focus on Outcomes after Cancer in a Racially Diverse Patient Population
Authors: Beebe-Dimmer Jennifer L. , Albrecht Terrance L. , Baird Tara E. , Ruterbusch Julie J. , Hastert Theresa , Harper Felicity W.K. , Simon Michael S. , Abrams Judith , Schwartz Kendra L. , Schwartz Ann G.
Published: November 2018

Background:

African Americans are often diagnosed with advanced stage cancer and experience higher mortality compared with whites in the United States. Contributing factors, like differences in access to medical care and the prevalence of comorbidities, do not entirely explain racial differences in outcomes.

Methods:

The Detroit Research on Cancer Survivors (ROCS) pilot study was conducted to investigate factors related to short- and long-term outcomes among patients with cancer. Participants completed web-based surveys, and mailed saliva specimens were collected for future genetic studies.

Results:

We recruited 1,000 participants with an overall response rate of 68%. Thirty-one percent completed the survey without any interviewer support and the remaining participated in an interviewer-administered survey. Seventy-four percent provided a saliva specimen and 64% consented for tumor tissue retrieval. African American survivors required more interviewer support (P < 0.001); however, their response rate (69.6%) was higher than non-Hispanic whites (65.4%). African Americans reported poorer overall cancer-related quality of life compared with non-Hispanic whites, measured by FACT-G score (P < 0.001), however, this relationship was reversed after controlling for socioeconomic factors, marital status, and the presence of comorbidities.

Conclusions:

In this pilot study, we demonstrated that a web-based survey supplemented with telephone interviews and mailed saliva kits are cost-effective methods to collect patient-reported data and DNA for large studies of cancer survivors with a high proportion of minority patients. The preliminary data collected reinforces differences by race in factors affecting cancer outcomes. Our efforts continue as we expand this unique cohort to include more than 5,000 African American cancer survivors.

Impact:

Formal investigation of factors influencing adverse outcomes among African American cancer survivors will be critical in closing the racial gap in morbidity and mortality.
Selenium and Sex Steroid Hormones in a U.S. Nationally Representative Sample of Men: A Role for the Link between Selenium and Estradiol in Prostate Carcinogenesis?
Authors: Van Hemelrijck Mieke , Sollie Sam , Nelson William G. , Yager James D. , Kanarek Norma F. , Dobs Adrian , Platz Elizabeth A. , Rohrmann Sabine
Published: November 2018

Background:

Given the recent findings from pooled studies about a potential inverse association between selenium levels and prostate cancer risk, this cross-sectional study aimed to investigate the association between serum selenium and serum concentrations of sex steroid hormones including estradiol in a nationally representative sample of U.S. men to investigate one mechanism by which selenium may influence prostate cancer risk.

Methods:

The study included 1,420 men ages 20 years or older who participated in the Third National Health and Nutrition Examination Survey between 1988 and 1994. We calculated age/race–ethnicity-adjusted and multivariable-adjusted geometric mean serum concentrations of total and estimated free testosterone and estradiol, androstanediol glucuronide, and sex hormone binding globulin, and compared them across quartiles of serum selenium.

Results:

Adjusting for age, race/ethnicity, smoking status, serum cotinine, household income, physical activity, alcohol consumption, and percent body fat, mean total estradiol [e.g., Q1, 38.00 pg/mL (95% confidence interval (CI), 36.03–40.08) vs. Q4, 35.29 pg/mL (95% CI, 33.53–37.14); Ptrend = 0.050] and free estradiol [e.g., Q1, 0.96 pg/mL (95% CI, 0.92–1.01) vs. Q4, 0.90 (95% CI, 0.85–0.95); Ptrend = 0.065] concentrations decreased over quartiles of selenium. Stratification by smoking and alcohol consumption, showed that the latter observation was stronger for never smokers (Pinteraction = 0.073) and those with limited alcohol intake (Pinteraction = 0.017). No associations were observed for the other sex steroid hormones studied.

Conclusions:

Our findings suggests that a possible mechanism by which selenium may be protective for prostate cancer is related to estrogen.

Impact:

Further studies of longitudinal measurements of serum and toenail selenium in relation to serum measurements of sex steroid hormones are needed.
Tumor-Contacted Neutrophils Promote Metastasis by a CD90-TIMP-1 Juxtacrine–Paracrine Loop
Authors: Wang Ying , Chen Jianing , Yang Linbin , Li Jiaqian , Wu Wei , Huang Min , Lin Ling , Su Shicheng
Published: November 2018

Purpose:

The different prognostic values of tumor-infiltrating neutrophils (TIN) in different tissue compartments are unknown. In this study, we investigated their different prognostic roles and the underlying mechanism.

Experimental Design: We evaluated CD66b+ neutrophils in primary tumors from 341 patients with breast cancer from Sun Yat-sen Memorial Hospital by IHC. The association between stromal and parenchymal neutrophil counts and clinical outcomes was assessed in a training set (170 samples), validated in an internal validation set (171 samples), and further confirmed in an external validation set (105 samples). In addition, we isolated TINs from clinical samples and screened the cytokine profile by antibody microarray. The interaction between neutrophils and tumor cells was investigated in transwell and 3D Matrigel coculture systems. The therapeutic potential of indicated cytokines was evaluated in tumor-bearing immunocompetent mice.

Results:

We observed that the neutrophils in tumor parenchyma, rather than those in stroma, were an independent poor prognostic factor in the training [HR = 5.00, 95% confidence interval (CI): 2.88–8.68, P < 0.001], internal validation (HR = 3.56, 95% CI: 2.07–6.14, P < 0.001), and external validation set (HR = 5.07, 95% CI: 2.27–11.33, P < 0.001). The mechanistic study revealed that neutrophils induced breast cancer epithelial–mesenchymal transition (EMT) via tissue inhibitor of matrix metalloprotease (TIMP-1). Reciprocally, breast cancer cells undergoing EMT enhanced neutrophils' TIMP-1 secretion by CD90 in a cell-contact manner. In vivo, TIMP-1 neutralization or CD90 blockade significantly reduced metastasis. More importantly, TIMP-1 and CD90 were positively correlated in breast cancer (r2 = 0.6079; P < 0.001) and associated with poor prognosis of patients.

Conclusions:

Our findings unravel a location-dictated interaction between tumor cells and neutrophils and provide a rationale for new antimetastasis treatments.
Targeting the Sphingosine 1-Phosphate Axis Exerts Potent Antitumor Activity in BRAFi-Resistant Melanomas
Authors: Garandeau David , Noujarède Justine , Leclerc Justine , Imbert Caroline , Garcia Virginie , Bats Marie-Lise , Rambow Florian , Gilhodes Julia , Filleron Thomas , Meyer Nicolas , Brayer Stéphanie , Arcucci Silvia , Tartare-Deckert Sophie , Ségui Bruno , Marine Jean-Christophe , Levade Thierry , Bertolotto Corine , Andrieu-Abadie Nathalie
Published: November 2018

BRAF inhibitors (BRAFi) are used to treat patients with melanoma harboring the V600E mutation. However, resistance to BRAFi is inevitable. Here, we identified sphingosine 1-phosphate (S1P) receptors as regulators of BRAFV600E-mutant melanoma cell-autonomous resistance to BRAFi. Moreover, our results reveal a distinct sphingolipid profile, that is, a tendency for increased very long-chain ceramide species, in the plasma of patients with melanoma who achieve a response to BRAFi therapy as compared with patients with progressive disease. Treatment with BRAFi resulted in a strong decrease in S1PR1/3 expression in sensitive but not in resistant cells. Genetic and pharmacologic interventions, that increase ceramide/S1P ratio, downregulated S1PR expression and blocked BRAFi-resistant melanoma cell growth. This effect was associated with a decreased expression of MITF and Bcl-2. Moreover, the BH3 mimetic ABT-737 improved the antitumor activity of approaches targeting S1P-metabolizing enzymes in BRAFi-resistant melanoma cells. Collectively, our findings indicate that targeting the S1P/S1PR axis could provide effective therapeutic options for patients with melanoma who relapse after BRAFi therapy.
ZEB1 Promotes Chemoresistance to Cisplatin in Ovarian Cancer Cells by Suppressing SLC3A2
Authors: Cui Yajie , Qin Li , Tian Defu , Wang Ting , Fan Lijing , Zhang Peilian , Wang Zhongqi
Published: November 2018

Ovarian cancer is one of the deadliest gynecological malignancies in women. Chemoresistance has been a major obstacle for ovarian cancer treatment. Zinc finger E-box-binding homeobox 1 (ZEB1) is an important regulator of tumor development in various types of cancer. Abnormal expression of SLC3A2 (CD98hc), a type 2 transmembrane cell surface molecule, has been described in several cancers. This study was designed to investigate the role of ZEB1 and SLC3A2 in the chemoresistance to cisplatin in ovarian cancer cells. We found that ZEB1 was increased in cisplatin-resistant SKOV3/DPP cells. Downregulation of ZEB1 significantly decreased cell viability in response to cisplatin, increased cis­platin-induced apoptosis, and decreased migration and invasion in the presence of cisplatin. In addition, downregulation of ZEB1 decreased the volume and weight of implanted tumors. SLC3A2 was decreased in cisplatin-resistant SKOV3/DPP cells. Upregulation of SLC3A2 significantly decreased cell viability in response to cisplatin, increased cisplatin-induced apoptosis, and decreased migration and invasion in the presence of cisplatin. Moreover, upregulation of SLC3A2 decreased the volume and weight of implanted tumors. Downregulation of ZEB1 resulted in a significant increase of SLC3A2 expression. Moreover, downregulation of SLC3A2 significantly inhibited ZEB1 knockdown-mediated inhibition of cisplatin-resistance. ZEB1-mediated regulation of SLC3A2 was involved in the chemoresistance to cisplatin in ovarian cancer cells. Overall, we provide new insights into the mechanism of chemoresistance to cisplatin in ovarian cancer cells. ZEB1/SLC3A2 may be promising therapeutic targets for enhancement of the sensitivity of ovarian cancer cells to cisplatin-mediated chemotherapy.
Platelet-Neutrophil Interactions Are Lower in Cord Blood of Premature Newborns
Authors: Esiaba Ijeoma , Angeles Danilyn M. , Milford Terry-Ann M. , Salto Lorena M. , Payne Kimberly J. , Kidder Melissa Y. , Boskovic Danilo S.
Published: November 2018

Objective: To quantify platelet-neutrophil interaction by flow cytometry, in newborn cord blood, as a function of gestational age. Rationale: Little is known about platelet function markers in the newborn, and developmental variations in these markers are not well described. Methods: Cord blood samples were obtained from 64 newborns between 23 and 40 weeks’ gestation. The neonates were grouped into three categories: preterm (< 34 weeks’ gestation, n = 21), late preterm (34 to < 37 weeks’ gestation, n = 22), and term (≥37 weeks’ gestation, n = 21). We monitored the expression of P-selectin and the formation of platelet-neutrophil aggregates (PNAs) by flow cytometry while using adenosine 5′-diphosphate (ADP) or thrombin receptor-activating peptide (TRAP) as agonists. Results: PNAs were significantly lower in preterm compared to term neonates after TRAP or ADP stimulations (11.5 ± 5.2% vs. 19.9 ± 9.1%, p < 0.001, or 24.0 ± 10.1% vs. 39.1 ± 18.2%, p = 0.008, respectively). The expression of P-selectin also tended to be lower in preterm neonates, with significant positive correlations between P-selectin expression and PNA formation. Conclusions: The potential formation of PNAs correlates with gestational age. This suggests that the development of functional competencies of platelets and neutrophils continues throughout gestation, progressively enabling interactions between them.
The Dépistage Cognitif de Québec: A New Clinician’s Tool for Early Recognition of Atypical Dementia
Authors: Sellami Leila , Meilleur-Durand Synthia , Chouinard Anne-Marie , Bergeron David , Verret Louis , Poulin Stéphane , Jean Léonie , Fortin Marie-Pierre , Nadeau Yannick , Molin Pierre , Caron Stéphanie , Macoir Joël , Hudon Carol , Bouchard Rémi W. , Laforce Jr. Robert
Published: November 2018

Introduction: Early recognition of atypical dementia remains challenging partly because of lack of cognitive screening instruments precisely tailored for this purpose. Methods: We assessed the validity and reliability of the Dépistage Cognitif de Québec (DCQ; www.dcqtest.org), a newly developed cognitive screening test, to detect atypical dementia using a multicenter cohort of 628 participants. Sensitivity and specificity were compared to the Montreal Cognitive Assessment (MoCA). A predictive diagnostic algorithm for atypical dementia was determined using classification tree analysis. Results: The DCQ showed excellent psychometric properties. It was significantly more accurate than the MoCA to detect atypical dementia. All correlations between DCQ indexes and standard neuropsychological measures were significant. A statistical model distinguished typical from atypical dementia with a predictive power of 79%. Discussion: The DCQ is a better tool to detect atypical dementia than standard cognitive screening tests. Expanding the clinician’s tool kit with the DCQ could reduce missed/delayed identification of atypical dementia and accelerate therapeutic intervention.
An Algorithm for Digital Medicine Testing: A NODE.Health Perspective Intended to Help Emerging Technology Companies and Healthcare Systems Navigate the Trial and Testing Period prior to Full-Scale Adoption
Authors: Sheon Amy R. , Van Winkle Brian , Solad Yauheni , Atreja Ashish
Published: November 2018

Over the last several years, there has been rapid growth of digital technologies attempting to transform healthcare. Unique features of digital medicine technology lead to both challenges and opportunities for testing and validation. Yet little guidance exists to help a health system decide whether to undertake a pilot test of new technology, move right to full-scale adoption or start somewhere in between. To navigate this complexity, this paper proposes an algorithm to help choose the best path toward validation and adoption. Special attention is paid to considering whether the needs of patients with limited digital skills, equipment (e.g., smartphones) and connectivity (e.g., data plans) have been considered in technology development and deployment. The algorithm reflects the collective experience of 20+ health systems and academic institutions that have established the Network of Digital Evidence for Health, NODE.Health, plus insights from existing clinical research taxonomies, syntheses or frameworks for assessing technology or for reporting clinical trials.
miR-650 Promotes the Metastasis and Epithelial–Mesenchymal Transition of Hepatocellular Carcinoma by Directly Inhibiting LATS2 Expression
Authors: Han Li Li , Yin Xiao Ran , Zhang Shu Qun
Published: November 2018

Background/Aims: Previous studies have confirmed that microRNAs are involved in the metastasis and epithelial–mesenchymal transition (EMT) of malignancies. In this study, we examined whether miR-650 promotes the migration, invasion, and EMT of hepatocellular carcinoma (HCC) cells by targeting the large tumor suppressor kinase 2 gene (LATS2). Methods: qRT-PCR was used to detect expression of miR-650 in HCC tissues and paired normal tissues. MTT and Transwell assay were used to observe the effect of miR-650 on proliferation, migration and invasion of HCC cells. Western blot assay and Immunohistochemistry were performed to demonstrate association between miR-650 expression level and epithelial-mesenchymal transition (EMT) related protein. Mechanistically, Reporter luciferase assay was performed to reveal whether large tumor suppressor kinase 2 (LATS2) was a direct target of miR-650 in HCC cells. Results: We observed that miR-650 levels were largely up-regulated in HCC tissues, and that the increased expression was closely associated with the adverse clinical features of HCC patients. Additionally, the expression of LATS2, which was identified as a direct target of miR-650, can counteract the effects of miR-650 in HCC. Furthermore, we demonstrated that high miR-650 expression levels and low LATS2 expression levels in tumors may indicate a poor prognosis for HCC patients. Conclusion: In conclusion, the miR-650/LATS2 pathway may serve as a novel prognostic biomarker and an attractive therapeutic target for HCC patients.
Long Non-Coding RNA XLOC_006753 Promotes the Development of Multidrug Resistance in Gastric Cancer Cells Through the PI3K/AKT/mTOR Signaling Pathway
Authors: Zeng Lisi , Liao Quanxing , Zou Zhaowei , Wen Yuefeng , Wang Jingshu , Liu Chang , He Qingjun , Weng Nuoqing , Zeng Judeng , Tang Hongsheng , Fang Runya , Lei Ziying , Tang Zhen , Yang Xianzi , Cui Shuzhong
Published: November 2018

Background/Aims: The development of multidrug resistance (MDR), which results in disease recurrence and metastasis, is a crucial obstacle to successful chemotherapy for patients with gastric cancer (GC). Long non-coding RNAs (lncRNAs) have been found to play various roles in cancer. This study aimed to investigate the effect of XLOC_006753 on the development of MDR in GC cells. Methods: The expression levels of XLOC_006753 in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell line) were assessed by qRT-PCR. Statistical analyses were conducted to determine the relationship between XLOC_006753 expression and clinical features and to assess the prognostic value of XLOC_006753 for overall survival and progression-free survival. Then, a CCK-8 assay was used to detect cell proliferation ability and chemosensitivity. Flow cytometry was used to detect cell cycle and cell apoptosis. A wound-healing assay and transwell assay were used to detect cell migration. The expression of markers for MDR, G1/S transition, epithelial–mesenchymal transition (EMT) and PI3K/ AKT/mTOR signaling pathway were examined by western blot. Results: XLOC_006753 was highly expressed in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell lines), and its high expression was positively associated with metastasis, TNM stage, tumor size, and poor survival in GC patients. Moreover, XLOC_006753 was an independent prognostic biomarker of overall survival and progression-free survival for gastric cancer patients. Knocking down XLOC_006753 in the two MDR GC cell lines significantly inhibited cell proliferation, cell viability, cell cycle G1/S transition, and migration. XLOC_006753 knockdown also promoted apoptosis. Furthermore, western blots showed that XLOC_006753 knockdown decreased some markers of MDR, G1/S transition, and EMT expression, while increasing caspase9 expression and inhibiting the PI3K/AKT/mTOR signaling pathway in SGC-7901/5-FU and SGC-7901/DDP cells. Conclusion: High expression of XLOC_006753 promoted the development of MDR, which was activated by the PI3K/AKT/mTOR pathway in GC cells.
Metformin Inhibited Growth, Invasion and Metastasis of Esophageal Squamous Cell Carcinoma in Vitro and in Vivo
Authors: Liang Feng , Wang Yu-Gang , Wang Changcheng
Published: November 2018

Background/Aims: This study aimed at investigating the effects of metformin on the growth and metastasis of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. Methods: Two human ESCC cell lines EC9706 and Eca109 were selected and challenged with metformin in this study. Western blot assay was performed to detect th level of Bcl-2, Bax and Caspase-3. Scratch wound assay, transwell assay and Millicell invasion assay were used to assay the invasion and migration of EC9706 and Eca109 cells. Nude mice tumor models were used to assay the growth and lung metastasis of ESCC cells after metformin treatment. The plasma glucose level was also assayed. Results: We found that metformin significantly inhibited proliferation and induced apoptosis of both ESCC cell lines in a dose- and time-dependent manner, and the expression of Bcl-2 was down-regulated and Bax and Caspase-3 were up-regulated. Metformin significantly inhibited the invasion and migration of EC9706 and Eca109 cells (p < 0.05). mRNA and protein levels of MMP-2 and MMP-9 decreased significantly upon treatment with metformin of 10mM for 12, 24 and 48h in a time-dependent manner (p < 0.05). In line with in vitro results, in vivo experiments demonstrated that metformin inhibited tumorigenicity, inhibited lung metastasis and down-regulated the expression of MMP-2 and MMP-9. Moreover, we showed that metformin treatment did not cause significant alteration in liver and renal functions and plasma glucose level. Conclusion: Our study for the first time demonstrated the anti-invasive and anti-metastatic effects of metformin on human ESCC cells both in vitro and in vivo, which might be associated with the down-regulation of MMP-2 and MMP-9. As a whole, our results indicate the potential of metformin to be developed as a chemotherapeutic agent for patients with ESCC and might stimulate future studies on this area.
A Heterozygous Missense hERG Mutation Associated with Early Repolarization Syndrome
Authors: Cheng Yun-Jiu , Yao Hao , Ji Cheng-Cheng , Chen Xu-Miao , Fan Jun , Liu Li-Juan , Wu Su-Hua
Published: November 2018

Background/Aims: Early repolarization syndrome (ERS) has been recently recognized as early repolarization pattern with idiopathic ventricular fibrillation. However, the genetic background of ERS has not been fully understood. Methods: A Chinese family with sudden cardiac death associated with ERS was investigated. Direct sequencing of ERS susceptibility genes was performed on the proband and family members. Whole-cell patch-clamp methods were used to characterize the mutant channel expressed in HEK 293 cells. Results: One missense mutation (p. K801T) was found in the hERG (KCNH2 gene) by the direct sequencing of candidate genes. Whole cell voltage clamp studies of the K801T mutation in HEK 293 cells demonstrated a 1.5-fold increase in maximum steady state current (37.2±7.3 vs 20.3±4.4 pA/pF) that occurred at a 20 mV more positive potential compared to the wild type channels. The voltage dependence of inactivation was significantly shifted in the positive voltage direction (WT -59.5±1.4 vs K801T -44.3±1.2 mV). Kinetic analysis revealed slower inactivation rates of K801T, but faster rates of activation and deactivation. The hERG channel blockers tested inhibited K801T-hERG channel in concentration response, and the potencies of these drugs can be rank-ordered as follows: quinidine> disopyramide> sotalol> flecainide. Conclusion: Our study indicated that the K801T mutation caused the gain of function of hERG channels that may account for the clinical phenotype of ERS. Quinidine and disopyramide could improve the function of K801T-hERG mutant channel, and may be therapeutic options for patients with the K801T hERG mutation.
Ginsenoside 20(S)-Rg3 Prevents PKM2-Targeting miR-324-5p from H19 Sponging to Antagonize the Warburg Effect in Ovarian Cancer Cells
Authors: Zheng Xia , Zhou Yuanyuan , Chen Wei , Chen Lihong , Lu Jiaojiao , He Fang , Li Xu , Zhao Le
Published: November 2018

Background/Aims: The Warburg effect is one of the main metabolic features for cancers, with long non-coding RNA (lncRNA) being involved as a class of crucial regulators. Our previous studies have shown that ginsenoside 20(S)-Rg3, an active saponin monomer extracted from red ginseng, inhibits the Warburg effect in ovarian cancer cells. However, the detailed lncRNA regulatory network modulated by 20(S)-Rg3 to prevent the Warburg effect in ovarian cancer cells has not been explored. Methods: High-throughput sequencing was used to screen out the differentially expressed lncRNAs between 20(S)-Rg3-treated and non-treated SKOV3 cells. The levels of lncRNA H19 and miR-324-5p were manipulated in SKOV3 and A2780, and the glucose consumption, lactate production and PKM2 protein level were detected. Dual-luciferase reporter assay and RIP were utilized to verify the direct binding of H19 to miR-324-5p and miR-324-5p to PKM2. Cell proliferation was examined by CCK8 and colony formation assay. Nude mice subcutaneous xenograft tumor models were established to evaluate the impact of miR-324-5p on tumor growth in vivo. Results: 20(S)-Rg3 downregulated 67 lncRNAs, and H19 was one of the most decreased lncRNAs. Suppression of H19 by siRNA transfection reduced glucose consumption, lactate production and PKM2 expression in ovarian cancer cells, while H19 overexpression in 20(S)-Rg3-treated ovarian cancer cells enhanced glucose consumption, lactate production and PKM2 expression. Dual-luciferase reporter assay and RIP results showed that H19 directly bound to miR-324-5p. Dual-luciferase reporter assay showed that miR-324-5p directly targeted PKM2, and miR-324-5p negatively regulated glucose consumption and lactate production in ovarian cancer cells. miR-324-5p overexpression inhibited cell proliferation in vitro and in vivo. Conclusion: Our study revealed that 20(S)-Rg3 blocked the competitive inhibition of H19 on miR-324-5p, which enhanced the suppression of miR-324-5p on PKM2 and therefore inhibited the Warburg effect and repressed tumorigenesis. In a word, 20(S)-Rg3 inhibited the Warburg effect in ovarian cancer cells via H19/miR-324-5p/PKM2 pathway.
Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma
Authors: Fei Dan , Zhang Xiaona , Liu Jinxiang , Tan Long , Xing Jie , Zhao Dongxu , Zhang Yang
Published: November 2018

Background/Aims: Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to play crucial regulatory roles in tumor progression. However, its clinical significance and biological role in osteosarcoma (OS) is completely unknown. The aim of the present study was to investigate the role of FER1L4 in OS progression and the underlying mechanism. Methods: We analyzed the expression levels of FER1L4 in tissues of OS patients and cell lines via quantitative RT-PCR (qRT-PCR). The effect of FER1L4 on cell proliferation, colony formation, migration and invasion was analyzed by cell counting kit-8 (CCK-8), colony formation, wound healing and transwell invasion assay, respectively. Novel targets of FER1L4 were selected through a bioinformatics soft and confirmed using a dual-luciferase reporter system and qRT-PCR. To detect the role of FER1L4 in vivo tumorigenesis, tumor xenografts were created. Results: We found that the expression of FER1L4 was significantly downregulated in OS tissues and cell lines; moreover, low expression of FER1L4 was associated with advanced tumor-nude-metastasis (TNM) stage, lymph node metastases, and poor overall survival. Functional assays showed that upregulation of FER1L4 significantly inhibited OS cell proliferation, colony formation, migration, and invasion in vitro, as well as suppressed tumor growth in vivo. Assays performed to determine the underlying mechanism, indicated that FER1L4 interacted directly with miR-18a-5p. Subsequently, we found that FER1L4 significantly increased PTEN expression, a known target of miR-18a-5p, in OS cells. Furthermore, PTEN was found to be down-regulated, and positively correlated with FER1L4 in OS tissues. Conclusion: These findings suggest that FER1L4, acting as a competing endogenous RNA (ceRNA) of miR-18a-5p, exerts its anti-cancer role by modulating the expression of PTEN. Thus, FER1L4 may be a novel target for the prevention and treatment of OS.
Avian fauna of Amboli Ghat, Sindhudurg District, Maharashtra State, India
Authors: Satose Varun , Choursiya Vikrant , Deulkar Rakesh , Menon Sasikumar
Published: November 2018

The present report puts forth a systematic checklist of bird species observed at Amboli Ghat in Maharashtra from 2009 to 2012, along with information on their status.  A total of 208 species were recorded, which is around 15% of bird species of the Indian subcontinent.  A family-wise analysis showed that the families Accipitridae and Muscicapidae (14 species each) followed by Ardeidae dominated the avifauna of the region.  The study also revealed that the area consisted of 11 species of birds that are classified under Near Threatened category and two under Vulnerable category of IUCN.  This study highlights the urgent need to conserve the biodiversity-rich area of Amboli Ghat with long-term plans.
Morphological variations in marine pufferfish and porcupinefish (Teleostei: Tetraodontiformes) from Tamil Nadu, southeastern coast of India
Authors: Kaleshkumar K. , Rajaram R. , Purushothaman P. , Arun G.
Published: November 2018

In the present study, morphological variations in 14 species of two families, Tetraodontidae and Diodontidae, were examined for individuals collected from five different centres in Tamil Nadu in the southeastern coast of India.  Twenty-seven morphological measurements and four meristic characters were taken and used for multivariate analyses such as discriminant function analysis (DFA) & MANOVA.  DFA revealed that the first two functions accounted for more than 75% variation between the species.  Negative allometric values were observed on head length (HL), orbital length (OL), pupil diameter (PD), interorbital length (IOL), pectoral-fin length (PEL), caudal peduncle depth (CPD), dorsal to pectoral fin distance (DPFD), caudal peduncle length (CPL) and post-pectoral-fin length (POPFL) measurements.  Also, MANOVA supported the DFA results.  Additions, allometric relationships, and meristic variations were observed for most of these species.   Moreover, this is the first attempt to describe a greater number of morphological features of the species belonging to the order Tetraodontiformes.