bluuebunny/crossref_metadata_2025 huggingface dataset:
Synrift magmatism in a Cenozoic rift basin from 3D seismic data, Wichianburi Sub-basin, Petchabun Basin, Thailand: part 2. How rift structure and stratigraphy modify intrusion morphology
Authors: Pongwapee Sopon , Won-in Krit , Morley Christopher K.
Published: August 2019

The Latest Oligocene–Pleistocene basic sheet intrusions in the Late Oligocene–Pliocene Wichianburi Sub-basin (onshore Thailand) and Eocene intrusions of the Ceduna Sub-basin (offshore southern Australia) provide examples of igneous intrusion architecture in rift and post-rift basin settings respectively that have been imaged by 3D seismic reflection data. These examples indicate that rift-related intrusions are overall smaller, have a higher aspect ratio, and tend to be more planar or transgressive in a single direction than the saucer-shaped sills that dominate in the post-rift setting of the Ceduna Sub-basin. The long-axis trend and dip direction of most sills in the rift setting investigated tend to conform with rift structure (i.e. fault strike directions and bedding dip and strike directions), and give a strong orientation bias, whereas orientations in the post-rift basin are more varied. The few saucer-shaped sills that formed in the Wichianburi Sub-basin are asymmetric and incompletely developed. A third area, the Kora region of the Taranaki Basin, is a region where intrusions are related to a volcanic centre. This gives the intrusions a mixture of circumferential and radial intrusions related to magmatic processes (e.g. loading by the volcanic edifice, magma chamber pressure) and rift-related influences. Rift-related sills commonly form stacked arrays. Fundamental factors that affect the morphology of sills include magma composition, volume, reservoir pressure and the mechanical stratigraphy of the host rocks. In rifts extra complexities affecting some sills, or parts of sills, include rift structure (faults, rotated, folded bedding), basin size and morphology, stress distribution and sedimentary architecture.

Supplementary material:
Thumbnail time–structure maps of 107 sills from the Wichianburi Sub-basin mapped from 3D seismic reflection data are available at
https://doi.org/10.6084/m9.figshare.c.4620101
The origin and pedogenesis of the Clay-with-flints Formation
Authors: Lawrence U.
Published: August 2019

The Clay-with-flints Formation outcrops on the high chalk plateaux and interfluves of the chalk downs in southern England. Both current and historical definitions of the Clay-with-flints are detailed and important distinctions are identified with other deposits that appear identical but are formed in different ways. Historically pedological or geomorphological studies have been carried out on the deposit. Engineering studies are only carried out where the deposit is crossed by infrastructure. The physical and chemical processes acting on the deposit and the resulting effects on the physical properties are discussed.
Assessing the Readiness of Academia in the Topic of False and Unverified Information
Authors: Fard Amir Ebrahimi , Cunningham Scott
Published: August 2019

The spread of false and unverified information has the potential to inflict damage by harming the reputation of individuals or organisations, shaking financial markets, and influencing crowd decisions in important events. This phenomenon needs to be properly curbed, otherwise it can contaminate other aspects of our social life. In this regard, academia as a key institution against false and unverified information is expected to play a pivotal role. Despite a great deal of research in this arena, the amount of progress by academia is not clear yet. This can lead to misjudgements about the performance of the topic of interest that can ultimately result in wrong science policies regarding academic efforts for quelling false and unverified information. In this research, we address this issue by assessing the readiness of academia in the topic of false and unverified information. To this end, we adopt the emergence framework and measure its dimensions (novelty, growth, coherence, and impact) over more than 21,000 articles published by academia about false and unverified information. Our results show the current body of research has had organic growth so far, which is not promising enough for confronting the problem of false and unverified information. To tackle this problem, we suggest an external push strategy that, compared to the early stages of the topic of interest, reinforces the emergence dimensions and leads to a higher level in every dimension.
The Clinical Spectrum of PTEN Mutations
Authors: Yehia Lamis , Keel Emma , Eng Charis
Published: August 2019

PTEN is a tumor suppressor gene that classically dampens the PI3K/AKT/mTOR growth-promoting signaling cascade. PTEN dysfunction causes dysregulation of this and other pathways, resulting in overgrowth. Cowden syndrome, a hereditary cancer predisposition and overgrowth disorder, was the first Mendelian condition associated with germline PTEN mutations. Since then, significant advances by the research and medical communities have elucidated how clinical phenotypic manifestations result from the underlying germline PTEN mutations. With time, it became evident that PTEN mutations can result in a broad phenotypic spectrum, causing seemingly disparate disorders from cancer to autism. Hence, the umbrella term of PTEN hamartoma tumor syndrome (PHTS) was coined. Timely diagnosis and understanding the natural history of PHTS are vital because early recognition enables gene-informed management, particularly as related to high-risk cancer surveillance and addressing the neurodevelopmental symptoms.
Vaccine against gastrin, a polyclonal antibody stimulator, decreases pancreatic cancer metastases
Authors: Osborne Nicholas , Sundseth Rebecca , Gay Martha D. , Cao Hong , Tucker Robin D. , Nadella Sandeep , Wang Shangzi , Liu Xunxian , Kroemer Alexander , Sutton Lynda , Cato Allen , Smith Jill P.
Published: August 2019

Growth of pancreatic cancer is stimulated by gastrin in both a paracrine and an autocrine fashion. Traditional therapies have not significantly improved survival, and recently pancreatic cancer has been deemed a “cold” tumor due to its poor response to immunotherapy. Strategies to improve survival of pancreatic cancer are desperately needed. In the current investigation, we studied the effects of an anti-gastrin cancer vaccine, polyclonal antibody stimulator (PAS; formerly called G17DT and Gastrimmune), used alone or in combination with a programmed cell death receptor (PD)-1 immune checkpoint antibody on pancreatic cancer growth, metastases, and the tumor microenvironment (TME). Immune-competent female C57BL/6 mice bearing syngeneic orthotopic murine pancreatic cancer treated with PAS had significantly smaller tumors and fewer metastases. Examination of the TME demonstrated decreased fibrosis with fewer M2 and more M1 tumor-associated macrophages. Expression of the E-cadherin gene was significantly increased and expression of the TGFβR2 gene was decreased compared with controls. Mice treated with PAS or the combination of PAS and PD-1 antibody exhibited significantly less tumor expression of phospho-paxillin, the focal adhesion protein β-catenin, and matrix metalloproteinase-7. This study suggests that inhibition of the cancer-promoting effects of gastrin in pancreatic cancer can decrease metastases by altering the TME and decreasing pathways that activate the epithelial mesenchymal transition. The PAS vaccine appears to change the TME, making it more susceptible to therapy with an immune checkpoint antibody. This novel combination of two immunotherapies may improve survival of pancreatic cancer by decreasing both tumor growth and metastasis formation.

NEW & NOTEWORTHY Survival from advanced pancreatic cancer is poor, in part due to dense fibrosis of the tumor microenvironment, increased number of M2-polarized macrophages that promote angiogenesis and invasion, and lack of “target-specific” therapy. Herein, we report that a tumor vaccine that selectively targets gastrin decreases pancreatic cancer growth and metastases. Furthermore, the gastrin vaccine polyclonal antibody stimulator alters the tumor microenvironment rendering it more responsive to immunotherapy with a programmed cell death receptor-1 immune checkpoint antibody.
The intensity order illusion: temporal order of different vibrotactile intensity causes systematic localization errors
Authors: Hoffmann Rebekka , Brinkhuis Manje A. B. , Unnthorsson Runar , Kristjánsson Árni
Published: August 2019

Haptic illusions serve as important tools for studying neurocognitive processing of touch and can be utilized in practical contexts. We report a new spatiotemporal haptic illusion that involves mislocalization when the order of vibrotactile intensity is manipulated. We tested two types of motors mounted in a 4 × 4 array in the lower thoracic region. We created apparent movement with two successive vibrotactile stimulations of varying distance (40, 20, or 0 mm) and direction (up, down, or same) while changing the temporal order of stimulation intensity (strong-weak vs. weak-strong). Participants judged the perceived direction of movement in a 2-alternative forced-choice task. The results suggest that varying the temporal order of vibrotactile stimuli with different intensity leads to systematic localization errors: when a strong-intensity stimulus was followed by a weak-intensity stimulus, the probability that participants perceived a downward movement increased, and vice versa. The illusion is so strong that the order of the strength of stimulation determined perception even when the actual presentation movement was the opposite. We then verified this “intensity order illusion” using an open response format where observers judged the orientation of an imaginary line drawn between two sequential tactor activations. The intensity order illusion reveals a strong bias in vibrotactile perception that has strong implications for the design of haptic information systems.

NEW & NOTEWORTHY We report a new illusion involving mislocalization of stimulation when the order of vibrotactile intensity is manipulated. When a strong-intensity stimulus follows a weak-intensity stimulus, the probability that participants perceive an upward movement increases, and vice versa. The illusion is so strong that the order of the strength of stimulation determined perception even when the actual presentation movement was the opposite. This illusion is important for the design of vibrotactile stimulation displays.
Fetal Growth Restriction Prediction: How to Move beyond
Authors: Leite Debora F. B. , Cecatti Jose G.
Published: August 2019

The actual burden and future burden of the small-for-gestational-age (SGA) babies turn their screening in pregnancy a question of major concern for clinicians and policymakers. Half of stillbirths are due to growth restrictionin utero, and possibly, a quarter of livebirths of low- and middle-income countries are SGA. Growing body of evidence shows their higher risk of adverse outcomes at any period of life, including increased rates of neurologic delay, noncommunicable chronic diseases (central obesity and metabolic syndrome), and mortality. Although there is no consensus regarding its definition, birthweight centile threshold, or follow-up, we believe birthweight <10thcentile is the most suitable cutoff for clinical and epidemiological purposes. Maternal clinical factors have modest predictive accuracy; being born SGA appears to be of transgenerational heredity. Addition of ultrasound parameters improves prediction models, especially using estimated fetal weight and abdominal circumference in the 3rdtrimester of pregnancy. Placental growth factor levels are decreased in SGA pregnancies, and it is the most promising biomarker in differentiating angiogenesis-related SGA from other causes. Unfortunately, however, only few societies recommend universal screening. SGA evaluation is the first step of a multidimensional approach, which includes adequate management and long-term follow-up of these newborns. Apart from only meliorating perinatal outcomes, we hypothesize SGA screening is a key for socioeconomic progress.
Circularly Polarized Omnidirectional Antenna with Dipole Core and Diagonally Adjoined Parasitic Braces for ISM Band Applications
Authors: Dangkham Piyapong , Dentri Sitthichai , Phongcharoenpanich Chuwong , Akkaraekthalin Prayoot
Published: August 2019

This research proposes a circularly polarized (CP) single-fed omnidirectional dipole antenna operable in 2.45 GHz frequency for the industrial, scientific, and medical (ISM) radio band applications. The proposed antenna consisted of bisectional dipole core, a pair of quarter-wave baluns, and four diagonally adjoined parasitic braces. The bisectional dipole core was utilized to improve the antenna gain and realize omnidirectional radiation pattern, and the quarter-wave baluns were to symmetrize the current on the bisectional core. The four parasitic braces collectively generated circular polarization. In the study, simulations were conducted using CST Microwave Studio and a prototype antenna fabricated. To validate, experiments were carried out, and simulation and experimental results compared. The finding revealed good agreement between the simulation and experimental results. Essentially, in addition to achieving an antenna gain of 2.07 dBic, the proposed CP single-fed omnidirectional antenna is suited to ISM frequency band applications.
Finite Integral Formulas Involving Multivariable Aleph-Functions
Authors: Tadesse Hagos , Suthar D. L. , Ayalew Minilik
Published: August 2019

The integrals evaluated are the products of multivariable Aleph-functions with algebraic functions, Jacobi polynomials, Legendre functions, Bessel-Maitland functions, and general class of polynomials. The main results of our paper are quite general in nature and competent at yielding a very large number of integrals involving polynomials and various special functions occurring in the problem of mathematical analysis and mathematical physics.
Effects of Soil Properties on the Performance of TRD Cut‐Off Wall
Authors: Zhang Peng , Song Haomin , Rui Kaijun , Li Juncai , Wang Shengnian
Published: August 2019

The trench cutting remixing deep wall (TRD) method is a new cement soil cut‐off wall construction technique, which has been widely used in cofferdam, embankment dam, and underground waterproof curtain structures. The chain cutter of TRD moves horizontally to cut and stir different soil layers by up and down to form a cement‐mixed soil diaphragm wall with continuous and uniform thickness, the mechanics and permeability of which are obviously different from those of cement soil with a horizontally mixed single soil layer in traditional deep mixing pile (DMP). In this paper, five sets of onsite walling tests with different cement ratios were carried out to analyse the unconfined compression and permeability of undisturbed cement‐mixed soil in TRD. The difference of both unconfined compressive and permeability coefficients in between TRD and DMP was analysed to discuss the stirring performance of TRD. Then, the microscopic mechanism of soil properties affecting the performance of cement‐mixed soil has been studied by scanning electron microscopy (SEM) in the unconfined compression strength test and permeability coefficient test of cement soil with different mixed soil properties. The test results show that the unconfined compressive strength of cement‐mixed soil is closely correlated to its gradation. As the mixed soil gradation curve approaches to the Fuller curve, the unconfined compressive strength would gradually increase. In mesoscopic, cement fine sand has a large pore structure, and the average pore area is 2.46 times as cement clay. The permeability coefficient of cement‐mixed soil is controlled by the proportion of fine sand content with high permeability.
Seismic Performance of Damaged Dovetail Joints with Different Damaged Degrees in Timber Frames
Authors: Ma Hua , Luan Xinyu , Li Zhenbao , Cui Haijian , Wang Wenjing , Song Jia
Published: August 2019

The mortise and tenon joints are the main connection forms used in ancient timber buildings, and damaged joints have a critical effect on the safety of a timber structure. There are three main damaged cases of dovetail joints which are pulling, contraction, and mixing damages. In this study, using a theoretical analysis of the stress distribution in a mortise and tenon joint resulted from the pullout damage, a theoretical equation for the resisting moment of the joint was proposed. A finite element model was used to simulate the cyclic displacement loading of a frame with intact joints and with different levels of pulling and contraction damaged joints. The results show that the moment capacities both for the test and the simulation were in good agreement with each other. The simulation results also indicated that there are no changes in the capacity and energy dissipation of the pulling damaged joint compared to that of the intact joint, and good seismic performance still was provided when the pulling damage was less than 2/5 of the joint length. However, the capacity of the contraction damaged joint was significantly reduced, and its seismic performance was tolerably lost. The seismic performance of a mixing damaged tenon with the same degree of pulling damage was between that of the pulling damaged tenon and the contraction damaged tenon, and generally, it was controlled by the contraction damage. The friction between the tenon and the mortise is the main source of resisting moment and energy dissipation ability.
The Registration of a Biomaser-Like Effect in an Enzyme System with an RTM Sensor
Authors: Ivanov Yu. D. , Malsagova K. A. , Vesnin S. G. , Tatur V. Yu. , Ivanova N. D. , Ziborov V. S.
Published: August 2019

The concentration dependence of a microwave frequency radiation from a solution of a functioning enzyme system (ES) (with the example of cytochrome P450 BM3 (CYP102A1) system during lauric acid (LA) hydroxylation) has been studied with a radiothermometric sensor. Registration of the radiation from the enzyme solution has been performed in the frequency range from 3.4 to 4.2 GHz at the enzyme concentrations from 10−10М to 10−6М. It has been demonstrated that the catalysis of LA hydroxylation in a reconstituted CYP102A1 system is accompanied by a generation of microwave radiation over the entire range of concentrations studied. It has been found that a transition from a multipulse mode (at nanomolar enzyme concentrations from 10−10М to 10−8М) to a single-pulse mode (at micromolar enzyme concentrations from 10−7М to 10−6М) is observed. This effect is discussed on the basis of assumptions considering possible realization of biomaser-like radiation in the enzyme system. The discovered concentration-based effect of the transition of an unsynchronized pulsed radiation into a synchronized one in ES can further be used in the development of novel methods of noninvasive diagnostics of diseases, in mathematical modeling of the functioning of living systems, and in the development of next-generation quantum computers.
Effects of Diet Based on IgG Elimination Combined with Probiotics on Migraine Plus Irritable Bowel Syndrome
Authors: Xie Yangzhi , Zhou Guijuan , Xu Yan , He Bing , Wang Yilin , Ma Rundong , Chang Yunqian , He Duanqun , Xu Chenlin , Xiao Zijian
Published: August 2019

Several research studies have revealed that migraine has a solid link with gastrointestinal diseases especially irritable bowel syndrome (IBS). This study was carried out to investigate therapeutic potential of diet based on IgG elimination combined with probiotics on migraine plus irritable bowel syndrome. A total of 60 patients diagnosed with migraine plus IBS were recruited for the study. IgG antibodies against 266 food varieties were detected by ELISA. Then, the subjects were randomized into three groups for treatment of IgG elimination diet or probiotics or diet combined with probiotics. Migraine symptom, gut function score, medication use, and serum serotonin level were measured at baseline, 7 weeks, and 14 weeks. Improvement of migraine and gut symptom was achieved at a certain time point. Reduced use of over-the-counter- (OTC−) analgesics was seen in all groups. However, use of triptans did not show significant difference. An increased serum serotonin level was seen in subjects treated with elimination diet and elimination diet combined with probiotics. IgG elimination diet combined with probiotics may be beneficial to migraine plus IBS. It may provide new insight by understanding the intricate relationship between migraine and gastrointestinal diseases.
Spatial-Temporal Analysis of Injury Severity with Geographically Weighted Panel Logistic Regression Model
Authors: Xiao Daiquan , Xu Xuecai , Duan Li
Published: August 2019

This study is intended to investigate the influencing factors of injury severity by considering the heterogeneity issue of unobserved factors at different arterials and the spatial attributes in geographically weighted regression models. To achieve the objectives, geographically weighted panel logistic regression model was developed, in which the geographically weighted logistic regression model addressed the injury severity from the spatial perspective, while the panel data model accommodated the heterogeneity attributed to unobserved factors from the temporal perspective. The geo-crash data of Las Vegas metropolitan area from 2014 to 2016 was collected, involving 27 arterials with 25,029 injury samples. By comparing the conventional logistic regression model and geographically weighted logistic regression models, the geographically weighted panel logistic regression model showed preference to the other models. Results revealed that four main factors, human-beings (drivers/pedestrians/cyclists), vehicles, roadway, and environment, were potentially significant factors of increasing the injury severity. The findings provide useful insights for practitioners and policy makers to improve safety along arterials.
Protective Effect and Mechanisms of New Gelatin on Chemotherapy-Induced Hematopoietic Injury Zebrafish Model
Authors: Han Liwen , Kong Haotian , Liu Fasheng , Li Xiaobin , Zhang Shanshan , Zhang Xuanming , Wu Yong , Yang Hua , Zhang Aiping , Liu Kechun
Published: August 2019

The aim of the study is to explore the protective effect of new gelatin (NG, Xin’ejiao in China) on hematopoietic injury caused by chemotherapy. Zebrafish, at 48 hours post fertilization (hpf), was treated with different chemotherapeutic drugs to establish the zebrafish hematopoietic damage model with reduced thrombocytes and erythrocytes. The protecting effects of NG on the thrombocytes and erythrocytes were observed, respectively, on zebrafish models. Then, the RT-PCR method was used to detect the change of mRNA level of the hematopoiesis-related cytokines scl1, c-myb, pu.1, GATA1, and runx1 genes. The results showed that 50 μg·mL−1 and 100 μg·mL−1 NG rescued and increased the thrombocytes numbers induced by vinorelbine (NVB) and chloramphenicol (CHL) and the erythrocytes numbers induced by methotrexate (MTX), doxorubicin (ADM), and mechlorethamine hydrochloride (MH) in zebrafish models. Meanwhile, the mRNA expression of scl1, c-myb, and GATA1 genes in the NG treatment group was raised compared with the MTX treatment group. Also, the mRNA expression of pu.1 and Runx1 in the NG treatment group was reduced compared with the MTX treatment group. In consequence, traditional Chinese medicine NG showed a certain degree protective effect on hematopoiesis injury induced by chemotherapy in this study, which may depend on the promotion of erythrocytes proliferation and the regulation of the hematopoietic genes level.
Short- and Mid-Term Prognosis of Patients Undergoing Rotational Atherectomy in Aortoostial Coronary Lesions in Left Main or Right Coronary Arteries
Authors: Quillot Marine , Carrié Didier , Lhermusier Thibault , Bouisset Frédéric , André Romain , Elbaz Meyer , Roncalli Jérôme , Campelo-Parada Francisco , Boudou Nicolas
Published: August 2019

Objective. To determine short-term and mid-term prognosis in patients with calcified ostial coronary lesions who underwent rotational atherectomy (RA). Background. RA was developed to facilitate stenting in complex lesions. Treatment of calcified aortoostial coronary lesions with RA appears to have poorer procedure outcomes than nonostial lesions; yet the literature on this topic is scarce. Methods. Of 498 consecutive patients who underwent RA, a total of 80 (16.1%) presented with aortoostial lesions. A comparative, monocentric study was performed between patients with aortoostial and nonaortoostial stenosis, in a retrospective registry. The primary endpoint was the procedural success rate. Secondary endpoints were the rates of major adverse cardiac and cardiovascular events (MACE) at 30 days and 24 months. Results. The procedural success rate was high and similar in patients with and without ostial lesions (96.3% vs 94.7%, p=0.78), as was the rate of angiographic complications (7.5% vs 8.4%, p=0.80). However, the 30-day mortality rate was significantly higher in the aortoostial group (11.3% vs 4.8%, p=0.04), as was the 24-month rate of MACE (43.8% vs 31.8%, p=0.04). The aortoostial location of the lesion was an independent factor associated with the occurrence of cardiovascular events at 24 months (HR = 1.52, 95% CI, 1.03-2.26, p=0.035). Conclusion. Procedural success and complication rates were similar in patients with and without aortoostial lesions. Despite a poor short- and mid-term prognosis, rotational atherectomy appears to be a feasible and safe treatment option for calcified aortoostial coronary lesions.
A Stacked BiLSTM Neural Network Based on Coattention Mechanism for Question Answering
Authors: Cai Linqin , Zhou Sitong , Yan Xun , Yuan Rongdi
Published: August 2019

Deep learning is the crucial technology in intelligent question answering research tasks. Nowadays, extensive studies on question answering have been conducted by adopting the methods of deep learning. The challenge is that it not only requires an effective semantic understanding model to generate a textual representation but also needs the consideration of semantic interaction between questions and answers simultaneously. In this paper, we propose a stacked Bidirectional Long Short-Term Memory (BiLSTM) neural network based on the coattention mechanism to extract the interaction between questions and answers, combining cosine similarity and Euclidean distance to score the question and answer sentences. Experiments are tested and evaluated on publicly available Text REtrieval Conference (TREC) 8-13 dataset and Wiki-QA dataset. Experimental results confirm that the proposed model is efficient and particularly it achieves a higher mean average precision (MAR) of 0.7613 and mean reciprocal rank (MRR) of 0.8401 on the TREC dataset.
Influence of Irradiation on Mechanical Properties of Nickel
Authors: Ma Lei , Li Changsheng , Shang Xue , Hu Wangyu
Published: August 2019

The influence of irradiation on mechanical properties of nickel is studied using molecular dynamics (MD) simulation. The single crystal nickel is irradiated with the primary knocked-on atom (PKA) energies of 5 keV, 10 keV, 20 keV, and 30 keV at 300 K, and then the tensile test is performed. The simulation results reveal that the yield strain and yield stress of irradiated nickel decrease with the irradiation energy increasing, while the elastic modulus has no obvious change at various irradiation energies. By analyzing the stress-strain curves and the microstructure evolution, it is found that the effect of irradiation accelerates the damage of the internal structure due to the existence of irradiation defects, and high-energy irradiation leads to the instability of the structure in the process of plastic deformation.
Targeting Glycolysis through Inhibition of Lactate Dehydrogenase Impairs Tumor Growth in Preclinical Models of Ewing Sarcoma
Authors: Yeung Choh , Gibson Anna E. , Issaq Sameer H. , Oshima Nobu , Baumgart Joshua T. , Edessa Leah D. , Rai Ganesha , Urban Daniel J. , Johnson Michelle S. , Benavides Gloria A. , Squadrito Giuseppe L. , Yohe Marielle E. , Lei Haiyan , Eldridge Sandy , Hamre John , Dowdy Tyrone , Ruiz-Rodado Victor , Lita Adrian , Mendoza Arnulfo , Shern Jack F. , Larion Mioara , Helman Lee J. , Stott Gordon M. , Krishna Murali C. , Hall Matthew D. , Darley-Usmar Victor , Neckers Leonard M. , Heske Christine M.
Published: August 2019

Altered cellular metabolism, including an increased dependence on aerobic glycolysis, is a hallmark of cancer. Despite the fact that this observation was first made nearly a century ago, effective therapeutic targeting of glycolysis in cancer has remained elusive. One potentially promising approach involves targeting the glycolytic enzyme lactate dehydrogenase (LDH), which is overexpressed and plays a critical role in several cancers. Here, we used a novel class of LDH inhibitors to demonstrate, for the first time, that Ewing sarcoma cells are exquisitely sensitive to inhibition of LDH. EWS-FLI1, the oncogenic driver of Ewing sarcoma, regulated LDH A (LDHA) expression. Genetic depletion of LDHA inhibited proliferation of Ewing sarcoma cells and induced apoptosis, phenocopying pharmacologic inhibition of LDH. LDH inhibitors affected Ewing sarcoma cell viability both in vitro and in vivo by reducing glycolysis. Intravenous administration of LDH inhibitors resulted in the greatest intratumoral drug accumulation, inducing tumor cell death and reducing tumor growth. The major dose-limiting toxicity observed was hemolysis, indicating that a narrow therapeutic window exists for these compounds. Taken together, these data suggest that targeting glycolysis through inhibition of LDH should be further investigated as a potential therapeutic approach for cancers such as Ewing sarcoma that exhibit oncogene-dependent expression of LDH and increased glycolysis.

Significance:

LDHA is a pharmacologically tractable EWS-FLI1 transcriptional target that regulates the glycolytic dependence of Ewing sarcoma.
Nanoparticle Encapsulation of Synergistic Immune Agonists Enables Systemic Codelivery to Tumor Sites and IFNβ-Driven Antitumor Immunity
Authors: Atukorale Prabhani U. , Raghunathan Shruti P. , Raguveer Vanitha , Moon Taylor J. , Zheng Carolyn , Bielecki Peter A. , Wiese Michelle L. , Goldberg Amy L. , Covarrubias Gil , Hoimes Christopher J. , Karathanasis Efstathios
Published: August 2019

Effective cancer immunotherapy depends on the robust activation of tumor-specific antigen-presenting cells (APC). Immune agonists encapsulated within nanoparticles (NP) can be delivered to tumor sites to generate powerful antitumor immune responses with minimal off-target dissemination. Systemic delivery enables widespread access to the microvasculature and draining to the APC-rich perivasculature. We developed an immuno-nanoparticle (immuno-NP) coloaded with cyclic diguanylate monophosphate, an agonist of the stimulator of interferon genes pathway, and monophosphoryl lipid A, and a Toll-like receptor 4 agonist, which synergize to produce high levels of type I IFNβ. Using a murine model of metastatic triple-negative breast cancer, systemic delivery of these immuno-NPs resulted in significant therapeutic outcomes due to extensive upregulation of APCs and natural killer cells in the blood and tumor compared with control treatments. These results indicate that NPs can facilitate systemic delivery of multiple immune-potentiating cargoes for effective APC-driven local and systemic antitumor immunity.

Significance:

Systemic administration of an immuno-nanoparticle in a murine breast tumor model drives a robust tumor site–specific APC response by delivering two synergistic immune-potentiating molecules, highlighting the potential of nanoparticles for immunotherapy.
ОКИСЛЮВАЛЬНИЙ СТРЕС ЯК ОДИН З ВАЖЛИВІШИХ ЧИННИКІВ ГОСТРОГО УРАЖЕННЯ ЕНДОТЕЛІЮ
Authors: Nikitin Ye. V. , Vereshchahinа O. I.
Published: August 2019

Метою роботи було дослідження динаміки вмісту циркулюючих ендотеліальних клітин у периферичній крові та визначення ролі процесів вільнорадикального окислення в пошкодженні ендотеліоцитів. На основі проведеного дослідження вдосконалити лікування хворих на грип А.

На підставі обстеження 158 пацієнтів віком від 18 до 45 років, хворих на грип А, з яких у 32 осіб ступінь тяжкості був легким, у 62 – середнім та у 64 хворих – тяжким, було встановлено взаємозв’язок між зростанням рівня циркулюючих ендотеліальних клітин і активністю процесів вільнорадикального окислення, показано ефективність комплексного лікування. На підставі проведених досліджень установлено, що в патогенезі грипу суттєву роль відіграє надмірне підвищення активності процесів перекисного окислення ліпідів зі зниженням рівня антиоксидантного захисту. Була встановлена пряма залежність між підвищеннями концентрації малонового діальдегіду, дієнових кон’югат і кетодієнів у крові хворих на грип з тяжким ступенем. При дослідженні циркулюючих ендотеліальних клітин також було виявлено збільшення їх загальної кількості залежно від ступеня тяжкості захворювання. Посилене відшарування ендотеліоцитів від базальної мембрани у групах дослідження є доказом поєднаної дії токсинів грипу та цитотоксичних продуктів вільнорадикального окислення. З метою зниження токсичного впливу продуктів перекисного окислення ліпідів (ПОЛ) при грипі 32 хворим із середнім ступенем тяжкості до базисної терапії додавали 2-етил-6-метил-3-гідроксипіридину сукцинат, механізм дії якого зумовлений його антиоксидантною та мембранопротекторною дією. Проведені дослідження дозволили дійти наступних висновків: дисбаланс у системі ПОЛ/АОЗ призводить до пригнічення та виснаження антиоксидантної системи, пошкодження ендотеліоцитів з подальшим розвитком дисфункції ендотелію; підвищення загальної кількості циркулюючих ендотеліальних клітин у крові розвивається у відповідь на оксидативний стрес; комплексний підхід до лікування грипу з призначенням препаратів з антирадикальним механізмом дії сприятливо впливає на перебіг захворювання та зменшує ураження ендотелію судин.
ANTIHERPETIC EFFICACY OF LACTOBACILLI AND BIFIDOBACTERIA PROBIOTIC STRAINS IN EXPERIMENTAL GENITAL HERPES IN GUINEA PIGS
Authors: Starosyla D. B. , Lazarenko L. M. , Hryhorieva S.M. , Babenko L. P. , Rybalko S. L. , Spivak M. Ya.
Published: August 2019

Метою було визначення антигерпетичної ефективності пробіотичного штаму Lacto­bacillus casei ІМВ В-7280 та композиції L. caseі ІМВ В-7280 – Bifidobacterium animalis VKL – B. animalis VKВ (В-7280 – VKL – VKВ) за експериментального генітального герпесу в мурчаків, індукованого вірусом простого герпесу 2-го типу (ВПГ-2).

Матеріали і методи. Генітальну герпетичну інфекцію моделювали за допомогою ВПГ-2 (штам ВН) у самиць безпородних мурчаків. Критеріями оцінки ступеня тяжкості інфекційного процесу були: площа і ступінь специфічних уражень, а також наявність набряку, гіперемії й виразок. У сироватці крові тварин визначали титр ВПГ-2 за допомогою загальноприйнятих вірусологічних методів дослідження. Спектр мікробіоти піхви тварин визначали за допомогою загальноприйнятих мікробіологічних методів дослідження. Ефективність дії пробіотичних бактерій оцінювали за максимального розвитку патологічного процесу: за згасанням клінічних проявів захворювання та інфекційного титру ТЦД ID50 ВПГ-2, а також скороченням термінів захворювання та індексом лікувальної дії (ІЛД).

Результати досліджень та їх обговорення. Встановлено, що за експериментального генітального герпесу у мурчаків при застосуванні пробіотичного штаму L. caseі ІМВ В-7280 та композиції В-7280 – VKL – VKВ зменшувались: ступінь клінічних симптомів захворювання, його тривалість, а також інфекційний титр ВПГ-2, хоч ІЛД не перевищував 50 %. Під впливом L. caseі ІМВ В-7280 та композиції відбувалось зменшення інфекційного титру ТЦД ID50 ВПГ-2, що свідчить про антигерпетичну ефективність цих пробіотичних штамів бактерій, у механізми якої може залучатись зміна мікробіоти піхви. Мікробіологічний пейзаж піхви за максимальної яскравості клінічних симптомів генітального герпесу характеризувався зниженням кількості стафілококів у піхві інфікованих мурчаків, яким вводили L. caseі ІМВ В-7280, при високому рівні цих бактерій за умови застосування композиції В-7280 – VKL – VKВ, а також появою в окремих тварин лактобацил (ЛАБ). Зауважимо, що виділені нами в кінці експерименту ЛАБ за своєю морфологією відрізнялися від лактобактерій, використаних в експерименті. Тобто можна припустити, що відбулося відновлення характерної для мурчаків нормальної мікробіоти піхви.

Висновок. Штам L. caseі ІМВ В-7280 та композиція В-7280 – VKL – VKВ є перспективними для розробки цільових пробіотиків для профілактики й лікування інфекційно-запальних хвороб сечостатевої системи.
МОРОЗОВА Н.С., МАРІЄВСЬКИЙ В.Ф. ДЕЗІНФЕКТОЛОГІЯ. СТЕРИЛІЗАЦІЯ, ДЕЗІНСЕКЦІЯ, ДЕРАТИЗАЦІЯ: ПІДРУЧНИК ДЛЯ СТУДЕНТІВ ВИЩИХ НАВЧАЛЬНИХ ЗАКЛАДІВ МЕДИЧНОГО ПРОФІЛЮ. – К.: НАУКОВА ДУМКА, 2019. – 240 с.
Authors: Andreychyn M. A.
Published: August 2019

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ОНТОЛОГО-КЕРОВАНІ ІНФОРМАЦІЙНІ СИСТЕМИ В ЗАБЕЗПЕЧЕННІ БЕЗПЕРЕРВНОГО ПРОФЕСІЙНОГО РОЗВИТКУ ЛІКАРІВ ТА ПРОВІЗОРІВ
Authors: Mintser O. P. , Popova M. A.
Published: August 2019

Стаття присвячена питанню забезпечення якості медичної освіти, підвищення кваліфікації медичних кадрів і безперервного професійного розвитку лікарів та провізорів засобами сучасних інформаційно-комунікаційних технологій. Визна­чені переваги застосування онтологічного підходу до представлення знань у процесі створення і використання медичних інформаційних систем з метою надання доступу до максимально повного обсягу інформації шляхом інтероперабельної інтеграції та агрегації знання-орієнтованих ресурсів та інформаційних джерел. Наведений короткий аналіз існуючих онтологій медичного призначення (від колекцій вузькоспеціалізованих тематичних онтологій до національних термінологічних систем охорони здоров’я), що виявив низку недоліків та перешкод їх використання в системі сучасної медичної освіти в Україні. Визначена необхідність створення єдиного середовища інтероперабельної взаємодії з існуючими онтологічними рішеннями засобами уніфікованого інтерфейсу користувача для підвищення ефективності безперервного професійного розвитку лікарів та провізорів. Викладені основні аспекти розробки онтолого-керованих інформаційних систем, що можуть бути використані не лише при проектуванні і розробці структури, функціоналу та інтерфейсів медичних інформаційних систем, а й у процесі їх використання для вирішення практичних завдань. Представлений досвід застосування ІТ-ТОДОС, когнітивні програмно-інформаційні засоби якої забезпечують інтерактивну інтероперабельну темпоральну та семантичну синхронізацію інформаційних ресурсів незалежно від формату, стандартів і технологій їх створення, для розробки та використання онтолого-керованих медичних інформаційних систем, наведений її функціонал та переваги використання в процесі забезпечення безперервного професійного розвитку лікарів та провізорів.
The Role of Career and Wage Incentives in Labor Productivity: Evidence from a Two-Stage Field Experiment in Malawi
Authors: Kim Hyuncheol Bryant , Kim Seonghoon , Kim Thomas T.
Published: August 2019

We study how career and wage incentives affect labor productivity through self-selection and incentive effect channels using a two-stage field experiment in Malawi. First, recent secondary school graduates were hired with either career or wage incentives. After employment, half of the workers with career incentives randomly received wage incentives, and half of the workers with wage incentives randomly received career incentives. Career incentives attract higher-performing workers than wage incentives do, but they do not increase productivity conditional on selection. Wage incentives increase productivity for those recruited through career incentives. Observable characteristics are limited in explaining selection effects of entry-level workers.
Win or Lose: Residential Sorting After a School Choice Lottery
Authors: Bibler Andrew , Billings Stephen B.
Published: August 2019

We examine residential relocation and opting out of the public school system in response to school choice lottery outcomes. We show that rising kindergartners and sixth graders who lose a school choice lottery are 6 percentage points more likely to exit the district or change neighborhood schools (20% to 30% increase) and make up 0.14 to 0.35 standard deviations in average school test scores between lottery assignment and attendance the following year. Using hedonic-based estimates of land prices, we estimate that lottery losers pay a 9% to 11% housing price premium for access to a school with a 1 standard deviation higher mean test score.
Disembodied Cognition and Assimilation: Thirteenth-Century Debates on an Epistemological Puzzle
Authors: Perler Dominik
Published: August 2019

Medieval Aristotelians assumed that we cannot assimilate forms unless our soul abstracts them from sensory images. But what about the disembodied soul that has no senses and hence no sensory images? How can it assimilate forms? This article discusses this problem, focusing on two thirteenth-century models. It first looks at Thomas Aquinas’ model, which invokes divine intervention: the separated soul receives forms directly from God. The article examines the problems this explanatory model poses and then turns to a second model, defended by Matthew of Aquasparta: the separated soul actively apprehends forms that are present to it. It will be argued that this model explains assimilation in terms of appropriation, rather than reception, of forms and thereby radically changes the traditional account of cognition. Finally, the article draws some methodological conclusions, arguing that the focus on the ‘limit case’ of separated souls made theoretical change possible.
A Critical Appraisal of Initial Coin Offerings
Authors: Nestarcova Dominika
Published: August 2019

Initial Coin Offerings (ICOs) emerged in 2017 as a revolutionary form of raising capital by technology companies and investment vehicles. ICOs enable start-up companies to issue blockchain-based assets (‘digital tokens’) to the public in return for a payment in cryptocurrencies or fiat money. The fundraising objective is to finance technology projects carried out by the ‘ICO issuer’. The ICO funding model represents a financial revolution as it provides additional pools of liquidity for capital formation purposes and a powerful tool for incentivizing communities through network effects. More importantly, the latent value of ICOs lies in the usage of the raised funds to develop cutting-edge distributed ledger technologies (DLTs). The advent of ICOs mushrooming worldwide promises to democratize financing, yet the commonly unregulated space in which ICOs operate, opens up a Pandora’s Box of investment and legal risks. The present paper argues that regulation needs to be goal-orientated and for that purpose, it is crucial to identify the nature of the ICO funding model, the cryptoeconomics behind it and the legal nature of digital tokens. With ICOs, academia, economists and regulators are at ground zero. Practitioners’ first instinct is to apply the knowledge of capital markets, but ICOs are a fundamentally new model of raising funds that have spawned different dynamics from ‘traditional’ capital markets. If we can establish how to approach ICOs within their own right, then choosing the correct regulatory stance will become a matter of identifying how ICOs and markets interact and how the investment risks can be allocated. Keeping with the spirit of ICOs as a financial innovation, the paper proposes self-regulation by ICO issuers to be a suitable regulatory approach, while limiting the role of regulators to policing the secondary market of crypto-intermediaries. For the purpose of fully rationalizing this position, the paper outlines the process of carrying out an ICO, relevant benefits and risks to the model, the current state of ICO regulation, digital token characterization and merits of different regulatory approaches.
An overview of the Onthophagini from the Arabian Peninsula (Coleoptera: Scarabaeoidea: Scarabaeidae)
Authors: ZIANI STEFANO , ABDEL-DAYEM MAHMOUD SALEH , ALDHAFER HATHAL MOHAMMED , BARBERO ENRICO
Published: August 2019

The onthophagine fauna of the Arabian Peninsula is reviewed. New data from public and private collections are given. The total number of Onthophagini known from the Peninsula now stands at 30 species, without taking into account dubious records, belonging to seven genera. Of these 30 species, three (Onthophagus aethiopicus d’Orbigny, 1902, O. falsus Gillet, 1925 and O. frontalis Raffray, 1877) are reported for the first time from the Arabian Peninsula, six species (Digitonthophagus eucatta Génier in Génier & Moretto, 2017, Onthophagus aethiopicus d’Orbigny, 1902, O. brittoni Paulian, 1948, O. falsus Gillet, 1925, O. rugulipennis Fairmaire, 1887, and O. trapezicornis d’Orbigny, 1902) are new records from Saudi Arabia, three (D. eucatta, O. aethiopicus and O. frontalis) are new from Yemen and five (O. bicolor Raffray, 1877, O. latipennis d’Orbigny, 1898, O. nitidulus Klug, 1856, O. quadriarmatus Fairmaire 1892 and O. sellatus Klug, 1845) are new from Oman. Furthermore, Onthophagus infuscatus Klug, 1845 is recorded from Djibouti for the first time. For all the treated species a general distribution, literature citations and eventual unpublished records are provided. A new synonymy (Onthophagus saudiensis Frey, 1962 under O. sticticus Harold, 1867) is proposed. Most of the species were recorded from locations in southern Saudi Arabia, Oman and Yemen, south Tropic of Cancer. Yemen and Saudi Arabia have the highest species numbers, hosting the richest fauna with 24 and 23 species, respectively. The majority of the Onthophagini fauna (73.33 %) has Afrotropical and Afrotropical-Palaearctic affinities, while the Palaearctic and Oriental-Palaearctic species are both represented by 6.66 %. The four Arabian endemisms represent the 13.33 % of the whole fauna. Lastly, a dichotomous key for the identification of Arabian onthophagine species is provided and a redescription of Onthophagus brittoni is supplied.
Redescription of Clubiona gongi Zhang, Yin, Bao & Kim, 1997 (Araneae: Clubionidae) with the first description of the male
Authors: YANG DAXING , ZHOU GUCHUN , YANG MAOFA , PENG XIANJIN
Published: August 2019

Clubiona Latreille, 1804 comprises 503 species across the world, of which 122 species were reported from China. Nearly one-third of Chinese species have been described with single-sex (World Spider Catalog, 2018). Twenty-eight species have been reported from Guizhou Province (Wang et al. 2015; Wu et al. 2015; Li & Lin 2016; Yu et al. 2017; Wang et al. 2018; Zhang et al. 2018).
Adelopsis diabolica, a new species of Ptomaphagini (Coleoptera: Leiodidae: Cholevinae) from São Paulo State, Brazil
Authors: GOMYDE EDUARDO C. , GNASPINI PEDRO
Published: August 2019

Adelopsis diabolica, new species (Coleoptera: Leiodidae: Cholevinae: Ptomaphagini) is described from Boracéia Biological Station, São Paulo State, Brazil. The apex of the male aedeagus is uniquely armed and diagnostic. Females have slightly expanded protarsomeres (less expanded than those of males), a very rare feature in the family.