bluuebunny/crossref_metadata_2025 huggingface dataset:
Management and Leadership in Advertising Agencies In Siauliai Region
Authors: Sologubas Simas
Published: July 2019

One can notice intense changes in modern advertising services’ market. Under the conditions of rapid technological changes, violent competition, and increased significance of human capital, advertising agencies face difficulties in covering and retaining the desirable position in the market. Advertising agencies have to react to factors of economic, social, technological environment and to stimulate the employment of human capital, managerial education. Managerial education should cover the development of leadership. It means that managers should educate themselves as leaders. It is a relevant condition for successful management. The manuscript aims at revealing the expression of leadership and management features in advertising agencies in Siauliai region. Theoretical analysis has shown that leadership is defined as relationships between leader and her followers. These relationships are based upon influence and aim at change implementation while pursuing common goals. Management is treated as knowledge and skills of managers. Knowledge and skills ensure the achievement of company’s goals and harmonious activity of congenial people and employees. It was found that a leader and a manager in an organization can be a different person. Results of empirical research has shown that majority of employees of advertising agencies in Siauliai region treat a leader as a person who takes responsibility and is inclined to take new activities in spite of given instructions. Leaders use current potential and seek for better results of activity. Majority of employees paid attention to one more important aspect of a leader, i.e. motivation to pursue common goals. One should notice the impact of a leader on employees during the process of the implementation of change. Results of the research confirmed that leader had a significant impact upon the success of the organization.Keywords: management, leadership, change management, human capital, advertising services.
Endothelial Cells Strengthening: Improving Functions in Management of Acute Coronary Syndrome (A Double Blind Randomized Interventional Control Trial)
Authors: Saxena Tarun , Patidar Sanjay , Verma Shailesh , Ozefa Ali Azeema , Saxena Manjari
Published: July 2019

Objective: Endothelial dysfunction/injury is the main reason for Acute Coronary Syndrome (ACS). Current therapy includes antiplatelet, lipid lowering and thrombus removal by drugs/ intervention. Endothelial strengthening in management of ACS is less narrated in literature. This study describes endothelial strengthening and clinical outcome in ACS with Triphala powder, a mixture of Amla (Phyllanthus emblica), Harad (Terminalia chebula), and Behda (Terminalia bellirica).
Methods: This is a double blind randomized interventional control trial. 80 cases coming to the emergency department were selected for study, divided into two groups. Group 1 (n=40, control), group 2 (n=40, study). Further subdivided into subgroup 1A and 2A ST-Elevation Myocardial Infarction (STEMI) and subgroup 1B and 2B Unstable Angina (UA). All subgroups were given clopidogrel, aspirin and atorvastatin and subjected to thrombolysis or Coronary Angiography (CAG) according to requirement. In addition study group was given Triphala powder 10 grams in a cup of water. Outcome was observed for relief in chest pain, ECG, Echocardiography changes at 50 minutes; (SSR) Sympathetic Skin Response was done initially. Statistical analysis was done by SPSS 20 software. Results: In intervention subgroups 2A and 2B there was significant relief in chest pain, settling down of ECG changes, and improvement in regional wall motion in echocardiography (p<0.001). There was increased sympathetic activity in all subgroups (spike response in SSR).
Conclusion: Sudden mismatch in ATP (Adenosine Triphosphate) supply results in endothelial dysfunction. It occurs primarily due to increase in sympathetic discharge. Endothelial dysfunction results in UA/STEMI. Triphala increases ATP synthesis by increasing mitochondrial capacity to maximum; strengthens endothelium which behaves like normal endothelium and resolves symptoms and signs of ACS.
Barriers to Agro-Ecological Intensification of Smallholder Upland Farming Systems in Lao PDR
Authors: Yap Von Yi , Xaphokhame Phaeng , de Neergaard Andreas , Bech Bruun Thilde
Published: July 2019

Intercropping of legumes can be a strategy to improve soil fertility and enhance overall productivity while reducing dependency on external inputs in intensified cropping systems. Integration of legumes in maize-based cropping systems is promoted as an agro-ecological intensification option for input-constrained smallholders in uplands of Southeast Asia, but adoption rates in the region remain low. The overall aim of this study was to assess the suitability and trade-offs of integrating ricebean in maize-based smallholder cropping systems in upland areas of Northern Laos. We conducted a researcher-managed field trial to investigate the agronomic performance of ricebean/maize intercropping, and farmer-managed trials combined with surveys (N = 97), and focus group discussions in 10 villages to understand factors influencing farmers’ decision making concerning ricebean adoption. Drought, rat infestation and crop damage by grazing livestock were identified as important constraints to the production of ricebeans. Factors facilitating adoption included improvement of soil fertility, the potentially high selling price of ricebeans and the presence of extension agents, while barriers included labour shortage, concerns about competition with maize and lack of a market outlet for the ricebean produce. We conclude that the investigated maize/ricebean intercropping system is poorly suited to the current conditions in the study area, and call for farm-based studies focusing on developing locally adapted legume intercropping systems able to perform under variable rainfall conditions. Initiatives addressing challenges related to free grazing livestock and efforts to link legume producers in remote areas to emerging markets are also needed.
AquaCropR: Crop Growth Model for R
Authors: Camargo Rodriguez Anyela Valentina , Ober Eric S.
Published: July 2019

The Food and Agriculture Organization (FAO) AquaCrop model, run either via a standalone graphical user interface (GUI) or via a matlab application programming interface (API) (AquaCrop-OS), has been successfully tested on many crop species and under multiple scenarios. However, with these current versions, it is difficult for users to adapt formulae, add functionality or incorporate the model into other applications such as decision support tools. Here, we report on the release of a version of AquaCrop written in R. Performance of the model was tested using published datasets of wheat (Triticum aestivum L.) and maize (Zea mays L.), comparing output from AquaCropR with these other versions of AquaCrop. Our goal in developing this version was to widen the use and improvement of AquaCrop through open access.
Genetic Diversity of Canine Babesia Species Prevalent in Pet Dogs of Punjab, Pakistan
Authors: Tayyub Muhammad , Ashraf Kamran , Lateef Muhammad , Anjum Aftab Ahmad , Ali Muhammad Asad , Ahmad Nisar , Nawaz Muhammad , Nazir Muhammad Mudasser
Published: July 2019

Canine babesiosis is a serious threat to dogs’ health worldwide, caused by the intra-erythrocytic Babesia species. The present study was carried out in pet dogs presented at three clinics of Lahore and one of Narowal in Punjab, Pakistan. Two hundred blood samples (50 from each clinic) were collected and screened by microscopy for Babesia spp. Out of 200 samples, 84 (42%) were found to be positive for babesiosis. The highest number of positive cases (50%) was recorded in dogs at Narowal clinic. Non-significant variation (p > 0.05) was observed in the prevalence of babesiosis in dogs in relation to sex and age. Positive samples were further confirmed by a polymerase chain reaction using 18S-rRNA genus-specific and species-specific primers. Amplicons were further analyzed by nucleotide sequencing for genetic diversity. Babesia canis and gibsoni were confirmed by genome sequencing in all diseased dogs. These isolates closely resembled each other, but differed from previous reported strains. In conclusion, pet dogs suffering from babesiosis were infected with B. canis and gibsoni, while in other countries, other Babesia species are also prevalent.
The Use of Chemotherapy to Prolong the Life of Dogs Suffering from Cancer: The Ethical Dilemma
Authors: Stephens Tanya
Published: July 2019

Despite the emergence some years ago of oncology as a veterinary specialty, there has been very little in the way of ethical debate on the use of chemotherapy in dogs. The purpose of this article is to undertake an ethical analysis to critically examine the use of chemotherapy to prolong the life of dogs suffering from cancer. If dogs have no concept of the future and are likely to suffer at least some adverse effects with such treatments, consideration should be given as to whether it is ethical and in the animal’s best interests to use chemotherapy. Chemotherapeutic drugs are mutagenic, carcinogenic, teratogenic and may be irritant. Furthermore, chemotherapy may involve multiple trips to the veterinarian, multiple procedures and periods in isolation. Cancer-associated pain has been shown to be under-diagnosed and pet owners overestimate the effects of chemotherapy on treatment survival time. Of additional concern is the public health risks associated with chemotherapeutic drugs. As chemotherapy is not generally considered curative, it is in effect palliative care. However, palliative care may not be in the best interests of a terminally ill animal. As the specialty of veterinary oncology continues to grow and as the use of chemotherapy becomes more commonplace in the treatment of animals with cancer, it is imperative that there is an ongoing ethical debate on the use of chemotherapy in animals.
High-Speed Holographic Shape and Full-Field Displacement Measurements of the Tympanic Membrane in Normal and Experimentally Simulated Pathological Ears
Authors: Tang Haimi , Razavi Payam , Pooladvand Koohyar , Psota Pavel , Maftoon Nima , Rosowski John J. , Furlong Cosme , Cheng Jeffrey T.
Published: July 2019

To improve the understanding of the middle-ear hearing mechanism and assist in the diagnosis of middle-ear diseases, we are developing a high-speed digital holographic (HDH) system to measure the shape and acoustically-induced transient displacements of the tympanic membrane (TM). In this paper, we performed measurements on cadaveric human ears with simulated common middle-ear pathologies. The frequency response function (FRF) of the normalized displacement by the stimulus (sound pressure) at each measured pixel point of the entire TM surface was calculated and the complex modal indicator function (CMIF) of the middle-ear system based on FRFs of the entire TM surface motions was used to differentiate different middle-ear pathologies. We also observed changes in the TM shape and the surface motion pattern before and after various middle-ear manipulations. The observations of distinguishable TM shapes and motion patterns in both time and frequency domains between normal and experimentally simulated pathological ears support the development of a quantitative clinical holography-based apparatus for diagnosing middle-ear pathologies.
A Real Distribution Network Voltage Regulation Incorporating Auto-Tap-Changer Pole Transformer Multiobjective Optimization
Authors: Danish Sayed Mir Shah , Shigenobu Ryuto , Kinjo Mitsunaga , Mandal Paras , Krishna Narayanan , Hemeida Ashraf Mohamed , Senjyu Tomonobu
Published: July 2019

A number of studies realized operation of power systems are unstable in developing countries due to misconfiguration of distribution systems, limited power transfer capability, inconsistency of renewable resources integration, paucity of control and protection measures, timeworn technologies, and disproportionately topology. This study underlines an Afghanistan case study with 40% power losses that is mainly pertinent from old distribution systems. The long length of distribution systems, low-power transfer capability, insufficient control and protection strategy, peak-demand elimination, and unstable operation (low energy quality and excessive voltage deviations) are perceived pre-eminent challenges of Afghanistan distribution systems. Some attainable solutions that fit challenges are remodeling (network reduction), networks reinforcement, optimum compensation strategy, reconfiguration options, improving, and transfer capability. This paper attempts to propose a viable solution using multiobjective optimization method of auto-tap-changer pole transformer (ATCTr). The proposed methodology in terms of optimal numbers and placement of ATCTr can be known as a novel two-dimensional solution. For this purpose, a real case of Kabul City distribution system is evaluated. Simulation results indicate the effectiveness of the proposed method in reducing system losses and improving system overall performance. This approach tends to regulate the voltage deviation in a proper and statutory range with minimum number and optimum placement of ATCTrs. The proposed method is simulated using MATLAB® environment to compare and evaluate performance of the proposed network under different situations and scenarios.
Coordinated Secondary Frequency Regulation Strategy of Doubly-Fed Induction Generator and Electric Vehicle
Authors: Zhang Qian , Li Yan , Li Chen , Ding Zhuwei , Xie Wenrui
Published: July 2019

Wind turbines can participate in frequency regulation by controlling active power output, but the indeterminacy and volatility of wind power result in low reliability of frequency support. Therefore, as a kind of energy storage system, an electric vehicle is adopted to coordinate with wind turbines to regulate system frequency considering its large-scale development. First, based on the reasonable division of wind speed regions and operation point selection of pitch angle, the de-loading strategy of doubly-fed induction generator for reserve capacity under continuously varying wind speed is proposed. Then, through the combination of rotor speed and pitch angle control, frequency regulation model of a doubly-fed induction generator in whole wind speed range is established. Finally, taking into account the driving demand of electric vehicle owners, through the real-time allocation of system frequency regulation task based on frequency regulation capacity, the coordinated control strategy of doubly-fed induction generator and electric vehicle cluster for secondary frequency regulation is put forward. The simulation results show that the coordinated frequency regulation strategy based on real-time allocation can suppress frequency deviation effectively, and the regulation effect is better than the situations of wind turbine coordinating with the conventional unit or coordinating with electric vehicle cluster based on fixed allocation ratio.
Recent Developments in Modulation Spectroscopy for Methane Detection Based on Tunable Diode Laser
Authors: Wang Fei , Jia Shuhai , Wang Yonglin , Tang Zhenhua
Published: July 2019

In this review, methane absorption characteristics mainly in the near-infrared region and typical types of currently available semiconductor lasers are described. Wavelength modulation spectroscopy (WMS), frequency modulation spectroscopy (FMS), and two-tone frequency modulation spectroscopy (TTFMS), as major techniques in modulation spectroscopy, are presented in combination with the application of methane detection.
Energy Management of Virtual Power Plant Considering Distributed Generation Sizing and Pricing
Authors: Maanavi Masoud , Najafi Arsalan , Godina Radu , Mahmoudian Mehrdad , M. G. Rodrigues Eduardo
Published: July 2019

The energy management of virtual power plants faces some fundamental challenges that make it complicated compared to conventional power plants, such as uncertainty in production, consumption, energy price, and availability of network components. Continuous monitoring and scaling of network gain status, using smart grids provides valuable instantaneous information about network conditions such as production, consumption, power lines, and network availability. Therefore, by creating a bidirectional communication between the energy management system and the grid users such as producers or energy applicants, it will afford a suitable platform to develop more efficient vector of the virtual power plant. The paper is treated with optimal sizing of DG units and the price of their electricity sales to achieve security issues and other technical considerations in the system. The ultimate goal in this study to determine the active demand power required to increase system loading capability and to withstand disturbances. The effect of different types of DG units in simulations is considered and then the efficiency of each equipment such as converters, wind turbines, electrolyzers, etc., is achieved to minimize the total operation cost and losses, improve voltage profiles, and address other security issues and reliability. The simulations are done in three cases and compared with HOMER software to validate the ability of proposed model.
Attributing Air Pollutant Exposure to Emission Sources with Proximity Sensing
Authors: Piedrahita Ricardo , Coffey Evan R. , Hagar Yolanda , Kanyomse Ernest , Verploeg Katelin , Wiedinmyer Christine , Dickinson Katherine L. , Oduro Abraham , Hannigan Michael P.
Published: July 2019

Biomass burning for home energy use contributes to negative health outcomes and environmental degradation. As part of the REACCTING study (Research on Emissions, Air quality, Climate, and Cooking Technologies in Northern Ghana), personal exposure to carbon monoxide (CO) was measured to gauge the effects of introducing two different cookstove types over four intervention groups. A novel Bluetooth Low-Energy (BLE) Beacon system was deployed on a subset of those CO measurement periods to estimate participants’ distances to their most-used cooking areas during the sampling periods. In addition to presenting methods and validation for the BLE Beacon system, here we present pollution exposure assessment modeling results using two different approaches, in which time-activity (proximity) data is used to: (1) better understand exposure and behaviors within and away from homes; and (2) predict personal exposure via microenvironment air quality measurements. Model fits were improved in both cases, demonstrating the benefits of the proximity measurements.
A Near-Field Gaussian Plume Inversion Flux Quantification Method, Applied to Unmanned Aerial Vehicle Sampling
Authors: Shah Adil , Allen Grant , Pitt Joseph R. , Ricketts Hugo , Williams Paul I. , Helmore Jonathan , Finlayson Andrew , Robinson Rod , Kabbabe Khristopher , Hollingsworth Peter , Rees-White Tristan C. , Beaven Richard , Scheutz Charlotte , Bourn Mark
Published: July 2019

The accurate quantification of methane emissions from point sources is required to better quantify emissions for sector-specific reporting and inventory validation. An unmanned aerial vehicle (UAV) serves as a platform to sample plumes near to source. This paper describes a near-field Gaussian plume inversion (NGI) flux technique, adapted for downwind sampling of turbulent plumes, by fitting a plume model to measured flux density in three spatial dimensions. The method was refined and tested using sample data acquired from eight UAV flights, which measured a controlled release of methane gas. Sampling was conducted to a maximum height of 31 m (i.e. above the maximum height of the emission plumes). The method applies a flux inversion to plumes sampled near point sources. To test the method, a series of random walk sampling simulations were used to derive an NGI upper uncertainty bound by quantifying systematic flux bias due to a limited spatial sampling extent typical for short-duration small UAV flights (less than 30 min). The development of the NGI method enables its future use to quantify methane emissions for point sources, facilitating future assessments of emissions from specific source-types and source areas. This allows for atmospheric measurement-based fluxes to be derived using downwind UAV sampling for relatively rapid flux analysis, without the need for access to difficult-to-reach areas.
Heroin Overdose-Related Child and Adolescent Hospitalizations: Insight on Comorbid Psychiatric and Substance Use Disorders
Authors: Queeneth Uwandu , Bhimanadham Narmada N. , Mainali Pranita , Onyeaka Henry K. , Pankaj Amaya , Patel Rikinkumar S.
Published: July 2019

Objective: To evaluate the association between psychiatric comorbidities, substance use disorders and heroin overdose-related hospitalizations (HOD). Next, to understand the demographic trend of HOD hospitalizations and comorbidities. Methods: Using the Nationwide Inpatient Sample (NIS), we included 27,442,808 child and adolescent hospitalizations, and 1432 inpatients (0.005%) were managed primarily for HOD. The odds ratio (OR) of the association of variables in HOD inpatients were measured using a logistic regression model. Results: Adolescents had 56 times higher odds (95% CI 43.36–73.30) for HOD-related hospitalizations compared to 4.6% children under 11 years. About three-fifth of the HOD inpatients were male, and they had 1.5-fold higher odds (95% CI 1.30–1.64) compared to 43% females in the study population. Whites were considerably higher in proportion (81%) than other race/ethnicities. A greater portion of HOD inpatients (40%) were from high-income families. Most common comorbid psychiatric disorders were mood (43.8%) and anxiety (20.4%). The prevalent comorbid substance use disorders were opioid (62.4%), tobacco (36.8%) and cannabis (28.5%) use disorders. Conclusion: HOD-related hospitalizations were predominant in males, White and older adolescents (12–18 years). Prescription opioids are the bridge to heroin abuse, thereby increasing the vulnerability to other substance abuse. This requires more surveillance and should be explored to help reduce the heroin epidemic in children.
Experimental Evaluation of the Ventilation Effectiveness of Corner Stratum Ventilation in an Office Environment
Authors: Ameen Arman , Choonya Gasper , Cehlin Mathias
Published: July 2019

An experimental study was conducted in a room resembling an office in a laboratory environment. The study involved investigating the ability of corner-placed stratum ventilation in order to evaluate the ventilation’s effectiveness and local thermal comfort. At fixed positions, the air temperature, air velocity, turbulence intensity, and tracer gas decay measurements were carried out. The results show that corner-placed stratum ventilation behaves very similar to a mixing ventilation system when considering air change effectiveness. The performance of the system was better at lower supply air flow rates for heat removal effectiveness. For the heating cases, the draught rates were all very low, with the maximum measured value of 12%. However, for the cooling cases, the maximum draught rate was 20% and occurred at ankle level in the middle of the room.
Electrodeposition of Cu–SWCNT Composites
Authors: Raja Pavan M. V. , Esquenazi Gibran L. , Gowenlock Cathren E. , Jones Daniel R. , Li Jianhua , Brinson Bruce , Barron Andrew R.
Published: July 2019

Single walled carbon nanotubes (SWCNTs) are used as a component of a plating solution of CuSO4 for direct current electrodeposition of Cu–SWCNT composites with varying nanotube proportions without the use of either a surfactant, a dispersing agent, or functionalization of the SWCNTs. The Cu–SWCNT composites are characterized by scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and Raman spectroscopy. The composites are comprised of metallic Cu and SWCNTs with minor oxide impurities, as well as the residual (Fe) catalyst from the unpurified SWCNTs, in addition to displaying nanotube-mediated morphological differences. EDX analysis of carbon (wt%) is close to quantitative with respect to the wt% of SWCNTs added to the electrolysis solution. The presence of SWCNTs decreases the oxidation of the copper, as well as changing the identity of the oxide from CuO, for electrolysis of Cu, to Cu2O. Hard adherent Cu–SWCNT coatings are prepared by the addition of Cu powder to the electrolysis solution. The approach described in this paper will enable controlled synthesis of metal-nanomaterial composites that can potentially be processed further into high ampacity electrical conductors.
Tumour Angiogenesis in Uveal Melanoma Is Related to Genetic Evolution
Authors: Brouwer Niels J. , Gezgin Gülçin , Wierenga Annemijn P.A. , Bronkhorst Inge H.G. , Marinkovic Marina , Luyten Gregorius P.M. , Versluis Mieke , Kroes Wilma G.M. , van der Velden Pieter A. , Verdijk Robert M. , Jager Martine J.
Published: July 2019

Increased angiogenesis is associated with a higher metastasis- and mortality rate in uveal melanoma (UM). Recently, it was demonstrated that genetic events, such as 8q-gain and BAP1-loss, influence the level of immune infiltrate. We aimed to determine whether genetic events, and specific cytokines, relate to angiogenesis in UM. Data from UM patients who underwent enucleation between 1999 and 2008 were analysed. Microvascular density (MVD) and the presence of infiltrating immune cells were determined with immunohistochemistry (IHC) and immunofluorescence in 43 cases. Chromosome status, BAP1 IHC and mRNA expression of angiogenesis-related genes were known in 54 cases. Tumours with monosomy 3/BAP1-loss showed a higher MVD compared to tumours with disomy 3/normal BAP1 expression (p = 0.008 and p = 0.004, respectively). Within BAP1-positive lesions (n = 20), 8q-gain did not relate to MVD (p = 0.51). A high MVD was associated with an increased expression of angiopoietin 2 (ANGPT2) (p = 0.041), Von Willebrand Factor (VWF) (p = 0.010), a decreased expression of vascular endothelial growth factor B (VEGF-B) (p = 0.024), and increased numbers of tumour-infiltrating macrophages (CD68+, p = 0.017; CD68+CD163+, p = 0.031) and lymphocytes (CD4+, p = 0.027). Concluding, vascular density of UM relates to its genetic profile: Monosomy 3 and BAP1-loss are associated with an increased MVD, while an early event (gain of 8q) is not independently related to MVD, but may initiate a preparation phase towards development of vessels. Interestingly, VEGF-B expression is decreased in UM with a high MVD.
Could Circulating Tumor Cells and ARV7 Detection Improve Clinical Decisions in Metastatic Castration-Resistant Prostate Cancer? The Istituto Nazionale dei Tumori (INT) Experience
Authors: Sepe Pierangela , Verzoni Elena , Miodini Patrizia , Claps Melanie , Ratta Raffaele , Martinetti Antonia , Mennitto Roberta , Sottotetti Elisa , Procopio Giuseppe , Cappelletti Vera , Daidone Maria Grazia
Published: July 2019

Enzalutamide and abiraterone have been shown to improve progression-free survival (PFS) and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients. Moreover, some patients may not benefit from the inhibition of androgen receptor (AR) activity or, alternatively, may develop secondary resistance. Detection in patients’ circulating tumor cells (CTCs) of ARV7, a splicing variant of AR lacking the ligand-binding domain, showed a link with treatment failure. Independent confirmation of the predictive role of CTC status combined with ARV7 detection is, therefore, a priority for extending personalized biomarker-driven treatments to all patients. In this prospective observational study, CTC status and the expression of AR and ARV7 were measured in 37 mCRPC patients, before starting treatment with enzalutamide or abiraterone, by employing commercially available kits. CTC status was positive in 21/37 patients: 46% and 24% of CTC-positive patients were defined as AR- and ARV7-positive, respectively. Kaplan–Meier estimates showed that positivity for each variable was significantly associated with poorer radiological PFS, PSA-PFS, and OS. All considered treatment outcomes worsened when going from CTC-negative to CTC-positive/ARV7-negative to CTC-positive/ARV7-positive patients, both in the global case series and in patients stratified into three groups based on basal PSA levels. Presently, technical approaches appear to be mature for introducing CTC/ARV7 tests in clinical practice.
Neoadjuvant Treatment in Locally Advanced Pancreatic Cancer (LAPC) Patients with FOLFIRINOX or Gemcitabine NabPaclitaxel: A Single-Center Experience and a Literature Review
Authors: Napolitano Fabiana , Formisano Luigi , Giardino Alessandro , Girelli Roberto , Servetto Alberto , Santaniello Antonio , Foschini Francesca , Marciano Roberta , Mozzillo Eleonora , Carratù Anna Chiara , Cascetta Priscilla , De Placido Pietro , De Placido Sabino , Bianco Roberto
Published: July 2019

The optimal therapeutic strategy for locally advanced pancreatic cancer patients (LAPC) has not yet been established. Our aim is to evaluate how surgery after neoadjuvant treatment with either FOLFIRINOX (FFN) or Gemcitabine-NabPaclitaxel (GemNab) affects the clinical outcome in these patients. LAPC patients treated at our institution were retrospectively analysed to reach this goal. The group characteristics were similar: 35 patients were treated with the FOLFIRINOX regimen and 21 patients with Gemcitabine Nab-Paclitaxel. The number of patients undergoing surgery was 14 in the FFN group (40%) and six in the GemNab group (28.6%). The median Disease-Free Survival (DFS) was 77.10 weeks in the FFN group and 58.65 weeks in the Gem Nab group (p = 0.625), while the median PFS in the unresected group was 49.4 weeks in the FFN group and 30.9 in the GemNab group (p = 0.0029, 95% CI 0.138–0.862, HR 0.345). The overall survival (OS) in the resected population needs a longer follow up to be completely assessed, while the median overall survival (mOS) in the FFN group was 72.10 weeks and 53.30 weeks for the GemNab group (p = 0.06) in the unresected population. Surgery is a valuable option for LAPC patients and it is able to induce a relevant survival advantage. FOLFIRINOX and Gem-NabPaclitaxel should be offered as first options to pancreatic cancer patients in the locally advanced setting.
Cancer Testis Antigens and Immunotherapy: Where Do We Stand in the Targeting of PRAME?
Authors: Al-Khadairi Ghaneya , Decock Julie
Published: July 2019

PRAME or PReferentially expressed Antigen in Melanoma is a testis-selective cancer testis antigen (CTA) with restricted expression in somatic tissues and re-expression in various cancers. It is one of the most widely studied CTAs and has been associated with the outcome and risk of metastasis. Although little is known about its pathophysiological function, PRAME has gained interest as a candidate target for immunotherapy. This review provides an update on our knowledge on PRAME expression and function in healthy and malignant cells and the current immunotherapeutic strategies targeting PRAME with their specific challenges and opportunities. We also highlight some of the features that position PRAME as a unique cancer testis antigen to target.
Hydrogen Production Improvement on Water Decomposition Through Internal Interfacial Charge Transfer in M3(PO4)2-M2P2O7 Mixed-Phase Catalyst (M = Co, Ni, and Cu)
Authors: Kim Junyeong , Heo Jun Neoung , Do Jeong Yeon , Yoon Seog Joon , Kim Youngsoo , Kang Misook
Published: July 2019

In this study, three types of Nasicon-type materials, Co3(PO4)2-CO2P2O7, Ni3(PO4)2-Ni2P2O7, and Cu3(PO4)2-Cu2P2O7, were synthesized as mixed-phase catalysts (MPCs) for evaluating their potential as new photocatalytic candidates (called Co3(PO4)2-CO2P2O7mpc, Ni3(PO4)2-Ni2P2O7mpc, and Cu3(PO4)2-Cu2P2O7mpc herein). Based on various physical properties, it was confirmed that there are two phases, M3(PO4)2 and M2P2O7, in which a similar phase equilibrium energy coexists. These colored powders showed UV and visible light responses suitable to our aim of developing 365-nm light-response photocatalysts for overall water-splitting. The photocatalytic performance of Ni2(PO4)3-Ni2P2O7 MPC showed negligible or no activity toward H2 evolution. However, Co2(PO4)3-Co2P2O7 MPC and Cu3(PO4)2-Cu2P2O7 MPC were determined as interesting materials because of their ability to absorb visible light within a suitable band. Moreover, an internal interface charge transfer was suggested to occur that would lower the recombination rate of electrons and holes. For Cu3(PO4)2-Cu2P2O7 MPC, the charge separation between the electron and hole was advantageously achieved, a water-splitting reaction was promoted, and hydrogen generation was considerably increased. The performance of a catalyst depended on the nature of the active metal added. In addition, the performance of the catalyst was improved when electrons migrated between the inter-phases despite the lack of a heterojunction with other crystals.
Never Travel Alone: The Crosstalk of Circulating Tumor Cells and the Blood Microenvironment
Authors: Heeke Simon , Mograbi Baharia , Alix-Panabières Catherine , Hofman Paul
Published: July 2019

Commonly, circulating tumor cells (CTCs) are described as source of metastasis in cancer patients. However, in this process cancer cells of the primary tumor site need to survive the physical and biological challenges in the blood stream before leaving the circulation to become the seed of a new metastatic site in distant parenchyma. Most of the CTCs released in the blood stream will not resist those challenges and will consequently fail to induce metastasis. A few of them, however, interact closely with other blood cells, such as neutrophils, platelets, and/or macrophages to survive in the blood stream. Recent studies demonstrated that the interaction and modulation of the blood microenvironment by CTCs is pivotal for the development of new metastasis, making it an interesting target for potential novel treatment strategies. This review will discuss the recent research on the processes in the blood microenvironment with CTCs and will outline currently investigated treatment strategies.
Fibroblast Growth Factor Receptor Functions in Glioblastoma
Authors: Jimenez-Pascual Ana , A. Siebzehnrubl Florian
Published: July 2019

Glioblastoma is the most lethal brain cancer in adults, with no known cure. This cancer is characterized by a pronounced genetic heterogeneity, but aberrant activation of receptor tyrosine kinase signaling is among the most frequent molecular alterations in glioblastoma. Somatic mutations of fibroblast growth factor receptors (FGFRs) are rare in these cancers, but many studies have documented that signaling through FGFRs impacts glioblastoma progression and patient survival. Small-molecule inhibitors of FGFR tyrosine kinases are currently being trialed, underlining the therapeutic potential of blocking this signaling pathway. Nevertheless, a comprehensive overview of the state of the art of the literature on FGFRs in glioblastoma is lacking. Here, we review the evidence for the biological functions of FGFRs in glioblastoma, as well as pharmacological approaches to targeting these receptors.
Novel Aspects of Extracellular Vesicles as Mediators of Cancer-Associated Thrombosis
Authors: Almeida Vitor H. , Rondon Araci M. R. , Gomes Tainá , Monteiro Robson Q.
Published: July 2019

The establishment of prothrombotic states during cancer progression is well reported but the precise mechanisms underlying this process remain elusive. A number of studies have implicated the presence of the clotting initiator protein, tissue factor (TF), in circulating tumor-derived extracellular vesicles (EVs) with thrombotic manifestations in certain cancer types. Tumor cells, as well as tumor-derived EVs, may activate and promote platelet aggregation by TF-dependent and independent pathways. Cancer cells and their secreted EVs may also facilitate the formation of neutrophil extracellular traps (NETs), which may contribute to thrombus development. Alternatively, the presence of polyphosphate (polyP) in tumor-derived EVs may promote thrombosis through a TF-independent route. We conclude that the contribution of EVs to cancer coagulopathy is quite complex, in which one or more mechanisms may take place in a certain cancer type. In this context, strategies that could attenuate the crosstalk between the proposed pro-hemostatic routes could potentially reduce cancer-associated thrombosis.
Impact of Tumour Hypoxia on Evofosfamide Sensitivity in Head and Neck Squamous Cell Carcinoma Patient-Derived Xenograft Models
Authors: Harms Julia K. , Lee Tet-Woo , Wang Tao , Lai Amy , Kee Dennis , Chaplin John M. , McIvor Nick P. , Hunter Francis W. , Macann Andrew M. J. , Wilson William R. , Jamieson Stephen M.F.
Published: July 2019

Tumour hypoxia is a marker of poor prognosis and failure of chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC), providing a strategy for therapeutic intervention in this setting. To evaluate the utility of the hypoxia-activated prodrug evofosfamide (TH-302) in HNSCC, we established ten early passage patient-derived xenograft (PDX) models of HNSCC that were characterised by their histopathology, hypoxia status, gene expression, and sensitivity to evofosfamide. All PDX models closely resembled the histology of the patient tumours they were derived from. Pimonidazole-positive tumour hypoxic fractions ranged from 1.7–7.9% in line with reported HNSCC clinical values, while mRNA expression of the Toustrup hypoxia gene signature showed close correlations between PDX and matched patient tumours, together suggesting the PDX models may accurately model clinical tumour hypoxia. Evofosfamide as a single agent (50 mg/kg IP, qd × 5 for three weeks) demonstrated antitumour efficacy that was variable across the PDX models, ranging from complete regressions in one p16-positive PDX model to lack of significant activity in the three most resistant models. Despite all PDX models showing evidence of tumour hypoxia, and hypoxia being essential for activation of evofosfamide, the antitumour activity of evofosfamide only weakly correlated with tumour hypoxia status determined by pimonidazole immunohistochemistry. Other candidate evofosfamide sensitivity genes—MKI67, POR, and SLFN11—did not strongly influence evofosfamide sensitivity in univariate analyses, although a weak significant relationship with MKI67 was observed, while SLFN11 expression was lost in PDX tumours. Overall, these data confirm that evofosfamide has antitumour activity in clinically-relevant PDX tumour models of HNSCC and support further clinical evaluation of this drug in HNSCC patients. Further research is required to identify those factors that, alongside hypoxia, can influence sensitivity to evofosfamide and could act as predictive biomarkers to support its use in precision medicine therapy of HNSCC.
Functional Analysis of the Ribosomal uL6 Protein of Saccharomyces cerevisiae
Authors: Borkiewicz Lidia , Mołoń Mateusz , Molestak Eliza , Grela Przemysław , Horbowicz-Drożdżal Patrycja , Wawiórka Leszek , Tchórzewski Marek
Published: July 2019

The genome-wide duplication event observed in eukaryotes represents an interesting biological phenomenon, extending the biological capacity of the genome at the expense of the same genetic material. For example, most ribosomal proteins in Saccharomyces cerevisiae are encoded by a pair of paralogous genes. It is thought that gene duplication may contribute to heterogeneity of the translational machinery; however, the exact biological function of this event has not been clarified. In this study, we have investigated the functional impact of one of the duplicated ribosomal proteins, uL6, on the translational apparatus together with its consequences for aging of yeast cells. Our data show that uL6 is not required for cell survival, although lack of this protein decreases the rate of growth and inhibits budding. The uL6 protein is critical for the efficient assembly of the ribosome 60S subunit, and the two uL6 isoforms most likely serve the same function, playing an important role in the adaptation of translational machinery performance to the metabolic needs of the cell. The deletion of a single uL6 gene significantly extends the lifespan but only in cells with a high metabolic rate. We conclude that the maintenance of two copies of the uL6 gene enables the cell to cope with the high demands for effective ribosome synthesis.
Inflammatory Bowel Disease Types Differ in Markers of Inflammation, Gut Barrier and in Specific Anti-Bacterial Response
Authors: Coufal Stepan , Galanova Natalie , Bajer Lukas , Gajdarova Zuzana , Schierova Dagmar , Jiraskova Zakostelska Zuzana , Kostovcikova Klara , Jackova Zuzana , Stehlikova Zuzana , Drastich Pavel , Tlaskalova-Hogenova Helena , Kverka Miloslav
Published: July 2019

Crohn’s disease (CD), ulcerative colitis (UC) and inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC-IBD), share three major pathogenetic mechanisms of inflammatory bowel disease (IBD)-gut dysbiosis, gut barrier failure and immune system dysregulation. While clinical differences among them are well known, the underlying mechanisms are less explored. To gain an insight into the IBD pathogenesis and to find a specific biomarker pattern for each of them, we used protein array, ELISA and flow cytometry to analyze serum biomarkers and specific anti-microbial B and T cell responses to the gut commensals. We found that decrease in matrix metalloproteinase (MMP)-9 and increase in MMP-14 are the strongest factors discriminating IBD patients from healthy subjects and that PSC-IBD patients have higher levels of Mannan-binding lectin, tissue inhibitor of metalloproteinases 1 (TIMP-1), CD14 and osteoprotegerin than patients with UC. Moreover, we found that low transforming growth factor-β1 (TGF-β1) is associated with disease relapse and low osteoprotegerin with anti-tumor necrosis factor-alpha (TNF-α) therapy. Patients with CD have significantly decreased antibody and increased T cell response mainly to genera Eubacterium, Faecalibacterium and Bacteroides. These results stress the importance of the gut barrier function and immune response to commensal bacteria and point at the specific differences in pathogenesis of PSC-IBD, UC and CD.
Intramolecular Domain Movements of Free and Bound pMHC and TCR Proteins: A Molecular Dynamics Simulation Study
Authors: Karch Rudolf , Stocsits Claudia , Ilieva Nevena , Schreiner Wolfgang
Published: July 2019

The interaction of antigenic peptides (p) and major histocompatibility complexes (pMHC) with T-cell receptors (TCR) is one of the most important steps during the immune response. Here we present a molecular dynamics simulation study of bound and unbound TCR and pMHC proteins of the LC13-HLA-B*44:05-pEEYLQAFTY complex to monitor differences in relative orientations and movements of domains between bound and unbound states of TCR-pMHC. We generated local coordinate systems for MHC α1- and MHC α2-helices and the variable T-cell receptor regions TCR Vα and TCR Vβ and monitored changes in the distances and mutual orientations of these domains. In comparison to unbound states, we found decreased inter-domain movements in the simulations of bound states. Moreover, increased conformational flexibility was observed for the MHC α2-helix, the peptide, and for the complementary determining regions of the TCR in TCR-unbound states as compared to TCR-bound states.
Primary Human Fibroblasts in Culture Switch to a Myofibroblast-Like Phenotype Independently of TGF Beta
Authors: Baranyi Ulrike , Winter Birgitta , Gugerell Alfred , Hegedus Balazs , Brostjan Christine , Laufer Günther , Messner Barbara
Published: July 2019

Fibroblasts are the prevalent cell type and main source for extracellular matrix (ECM) in connective tissue. Depending on their origin, fibroblasts play a central role in non-pathological tissue remodeling and disease like fibrosis. This study examined the effect of established culture conditions of primary human fibroblasts, from different origins on the myofibroblast-like phenotype formation. We isolated primary human fibroblasts from aortic adventitia, lung, juvenile- and adult skin and investigated the expression levels of CD90, alpha smooth muscle actin (αSMA) and procollagen I under different concentrations of fetal calf serum (FCS) and ascorbic acid (AA) in culture media by immunoblot and immunofluorescence assays. Furthermore, we determined the viability using XTT and migration/wound healing in scratch assays. Collagen 1 secretion was quantified by specific ELISA. Primary human fibroblasts show in part a myofibroblast-like phenotype even without addition of FCS. Supplemented AA reduces migration of cultured fibroblasts with no or low concentrations of FCS. Furthermore, AA and higher concentrations of FCS in culture media lead to higher levels of collagen 1 secretion instead of procollagen I accumulation. This study provides evidence for a partial switch of primary human fibroblasts of different origin to a myofibroblast-like phenotype under common culture conditions.
Insights from Mathematical Modelling into Energy Requirement and Process Design of Continuous and Batch Stirred Tank Aerobic Bioreactors
Authors: Fitzpatrick John J.
Published: July 2019

Bioreaction kinetics, oxygen transfer and energy modelling were applied to stirred tank aerobic bioreactors. This was done to investigate how key input design variables influence bioreactor size, feed and wasted substrate, and electrical energy requirements for aeration and cooling, and to compare batch and continuous modes of operation. Oxygen concentration in the liquid is a key input design variable, but its selection is challenging as it can result in design trade-offs. Reducing its value caused a decrease in electrical energy requirement, however this tended to increase the working volume of the bioreactor. The minimum or near-to-minimum total energy requirement for oxygen transfer occurred when operating at the onset of flooding throughout the bioreaction time. For typical KS values, continuous mode of operation required a much smaller bioreactor volume, due to higher operating cell concentration, and this is a major advantage of continuous over batch.
Enhancement of Critical Current Density by Establishing a YBa2Cu3O7−x/LaAlO3/YBa2Cu3O7−x Quasi-Trilayer Architecture Using the Sol-Gel Method
Authors: Wu Chuanbao , Wang Yunwei
Published: July 2019

We developed a solution-derived method to establish a YBa2Cu3O7−x/LaAlO3/YBa2Cu3O7−x quasi-trilayer architecture. Using the method, nano-scale pinning sites were induced into the quasi-trilayer architecture and yielded an apparent improvement in the in-field critical current density (Jc) of high-quality YBa2Cu3O7−x (YBCO). The improvement in the in-field Jc of the films was closely related to the thickness of the LaAlO3 (LAO) interlayer. In this paper it is demonstrated that when the nominal interlayer thickness approximates 20 nm, which is slightly higher than the roughness of the YBa2Cu3O7−x surface, the LaAlO3 interlayer is discontinuous due to synchromesh-like growth of the LaAlO3 layer on relatively rough YBa2Cu3O7−x surface resulting from the mobility of the solution. Nanoscale defects, such as particles, some amorphous phases, and especially their concomitant lattice defects (such as stacking faults and plane buckling) arise in YBa2Cu3O7−x layers. These nanoscale defects could play a role in flux pinning and thus enhancing Jc. The effective non-vacuum solution to induce vortex pinning into YBa2Cu3O7−x films could be a reference for the further design of an optimal pinning landscape for higher Jc.