bluuebunny/crossref_metadata_2025 huggingface dataset:
A Numerical Model of an Acoustic Metamaterial Using the Boundary Element Method Including Viscous and Thermal Losses
Authors: Henríquez V. Cutanda , Andersen P. Risby , Jensen J. Søndergaard , Juhl P. Møller , Sánchez-Dehesa J.
Published: November 2016

In recent years, boundary element method (BEM) and finite element method (FEM) implementations of acoustics in fluids with viscous and thermal losses have been developed. They are based on the linearized Navier–Stokes equations with no flow. In this paper, such models with acoustic losses are applied to an acoustic metamaterial. Metamaterials are structures formed by smaller, usually periodic, units showing remarkable physical properties when observed as a whole. Acoustic losses are relevant in metamaterials in the millimeter scale. In addition, their geometry is intricate and challenging for numerical implementation. The results are compared with existing measurements.
Modeling of Propagation of Antiplane Acoustic Waves in Multiscale Media with Lognormal Distribution of Parameters
Authors: Soboleva Olga
Published: November 2016

The effective coefficients for the problem of propagation of acoustic waves in multifractal elastic media using the subgrid modeling approach are obtained. The maximum scale of heterogeneities of the medium in question is assumed to be small as compared with the wavelength. If a isotropic medium is assumed to satisfy the improved Kolmogorov similarity hypothesis, the term for the effective coefficient of the elastic stiffness coincides with the Landau–Lifshitz–Matheron formula. Both isotropic and anisotropic media are considered. The numerical testing for the wave propagating at a distance, which is of the same order as a typical wavelength of a source, illustrates the efficiency of the approach proposed.
INDUCED ELECTRODEPOSITION OF AMORPHOUS MOLYBDENUM (IV) OXIDE FILM BY Ni2+ AND ITS ABILITY OF LITHIUM STORAGE
Authors: SU CHANGWEI , YE MENGCHAO , BAI YANG , HOU JIANPING , GUO JUNMING
Published: November 2016

Amorphous molybdenum oxide films with almost 20[Formula: see text][Formula: see text]m thickness are electrodeposited on the Cu foils from a citrate-ammonia molybdate bath containing Ni[Formula: see text] ions. The content of Ni in the oxide films is very low, 0.87 at.%. XRD and FTIR data suggest that they are composed of hydrous MoO2. The multilayer and cracked structures are characterized by scanning electron microscopy (SEM), and are beneficial to transmission of Li[Formula: see text] ions between the electrolyte and anode materials. Galvanostatic battery testing shows that amorphous molybdenum (IV) oxides as anodes for lithium-ion batteries exhibit a high specific capacity of 876[Formula: see text]mA[Formula: see text]h[Formula: see text]g[Formula: see text] at a current density of 50[Formula: see text]mA[Formula: see text]g[Formula: see text], good capacity retention as high as 97.4% after 20 cycles.
An Enriched Edge-Based Smoothed FEM for Linear Elastic Fracture Problems
Authors: Yang Yongtao , Zheng Hong , Du Xiuli
Published: November 2016

Based on the edge-based smoothed FEM (ES-FEM) and the partition of unity, the first major items of Williams’ series for the displacement field near the crack tip are incorporated in the test and trial function space, resulting in the enriched ES-FEM formulation, eEF-FEM. The eES-FEM does not differentiate any shape functions, avoiding the treatment of the [Formula: see text] singularity in computing the stiffness matrix. The complexity of computation is accordingly reduced. Meanwhile, it is pointed out that the variational foundation of the eES-FEM is the generalized Galerkin method. Typical numerical examples are analyzed, suggesting that the results of the eES-FEM are much better than either FEM or ES-FEM.
Delicacies for a Privileged Class in a Risk Society: The Chinese Communist Party’s Special Supplies Food System
Authors: TSAI WEN-HSUAN
Published: November 2016

This paper discusses the history and operation of the tegong (special supplies) system for foodstuffs operated by the Chinese Communist Party (CCP). The system has been in existence since the Yan’an period and is still being practiced today. It was originally introduced to deal with China’s shortage economy during the era of Mao Zedong. Nowadays, the issue of food safety has made China a risk society, making it necessary for the CCP to provide its privileged class with food that is safe for consumption. We distinguish two categories of food supplies in terms of their operation: dedicated supplies for special needs and routine tegong. In addition, we believe that an alliance relationship between the government and food enterprises has emerged within the tegong system, with government officials and businesses colluding to their mutual benefit and profit. The paper concludes that the continuation of the tegong system signifies the persistence of a high degree of social inequality in modern-day China.
PRODUCT LAUNCH PERFORMANCE IN HI-TECH SMEs: NEWNESS TO THE FIRM AND THE ROLE OF MANAGEMENT CONTROLS
Authors: WILLIAMS CHRISTOPHER , VAN TRIEST SANDER
Published: November 2016

We investigate the impact of management control mechanisms on the success of new product launches in high-technology small- and medium-sized enterprises (SMEs). We argue that internal management controls will alleviate problems associated with product newness. Using survey data from 76 SMEs we find newness to the firm to be negatively related to product launch success, while the use of informal and formal controls have positive effects. Furthermore, informal controls within the SME moderate the negative relationship between newness and launch success. The results add to the debate on the impact of control mechanisms on innovative activities in SMEs.
Visible light driven photocatalytic activity of Fe-doped ZnO nanocrystals
Authors: Zhai Bao-Gai , Yang Long , Ma Qing-Lan , Huang Yuan Ming
Published: November 2016

Fe-doped ZnO nanocrystals at the level of 8[Formula: see text]mol% were synthesized via the co-precipitation method and then characterized by transmission electron microscopy, X-ray diffraction, diffuse reflectance spectroscopy and UV–Vis absorption spectroscopy. Strong absorptions with its peak at around 500[Formula: see text]nm were recorded in the range of 400–600[Formula: see text]nm for Fe-doped ZnO nanocrystals. Visible-light driven photocatalytic activity of Fe-doped ZnO nanocrystals was demonstrated via the photocatalytic degradation of methyl orange dye. Density functional calculations show that Fe dopant can generate a deep trap level at Ev [Formula: see text] 1.01[Formula: see text]eV in the bandgap of ZnO, which is believed to be responsible for the visible light responsive photocatalytic activity of Fe-doped ZnO.
Causes and mitigation strategies of surface hydrocarbon leaks at heavy-oil fields: examples from Alberta and California
Authors: Schultz Richard A.
Published: November 2016

Identification and mitigation of leaks of subsurface fluids such as hydrocarbons at many heavy-oil fields is a first-order concern to operating companies, their regulators and the public. A variety of leaks have been documented at heavy-oil fields in Alberta (Canada) and California (USA). Although the petroleum geology and tectonic framework of fields in these areas differ significantly, production-related uplift of overburden and dilation of pre-existing fractures due to cyclic steam injection are likely to have facilitated the leakage events. As a result, integration of overburden characterization and monitoring with management of steam pressures may provide an effective means of risk mitigation of major leakage events.
Fourth-ventricle leptin infusions dose-dependently activate hypothalamic signal transducer and activator of transcription 3
Authors: Harris Ruth B. S. , Desai Bhavna N.
Published: November 2016

Previous studies have shown that very low-dose infusions of leptin into the third or the fourth ventricle alone have little effect on energy balance, but simultaneous low-dose infusions cause rapid weight loss and increased phosphorylation of STAT3 (p-STAT3) in hypothalamic sites that express leptin receptors. Other studies show that injecting high doses of leptin into the fourth ventricle inhibits food intake and weight gain. Therefore, we tested whether fourth-ventricle leptin infusions that cause weight loss are associated with increased leptin signaling in the hypothalamus. In a dose response study 14-day infusions of increasing doses of leptin showed significant hypophagia, weight loss, and increased hypothalamic p-STAT3 in rats receiving at least 0.9 μg leptin/day. In a second study 0.6 μg leptin/day transiently inhibited food intake and reduced carcass fat, but had no significant effect on energy expenditure. In a final study, we identified the localization of STAT3 activation in the hypothalamus of rats receiving 0, 0.3, or 1.2 μg leptin/day. The high dose of leptin, which caused weight loss in the first experiment, increased p-STAT3 in the ventromedial, dorsomedial, and arcuate nuclei of the hypothalamus. The low dose that increased brown fat UCP1 but did not affect body composition in the first experiment had little effect on hypothalamic p-STAT3. We propose that hindbrain leptin increases the precision of control of energy balance by lowering the threshold for leptin signaling in the forebrain. Further studies are needed to directly test this hypothesis.
Prevalence of Hepatitis C Virus Seropositivity and Its Impact on Coronary Artery Disease among Egyptian Patients Referred for Coronary Angiography
Authors: Salam Ragab Abd El , Nabil Baher , Saber Marawan , AbdelWahab Hany A. , Saber Tamer
Published: November 2016

Background. We tested the prevalence and impact of HCV seropositivity among Egyptian patients referred for coronary angiography. Subjects and Methods. This cross-sectional study was conducted in Zagazig University hospitals including 509 patients scheduled for elective coronary angiography between June 2013 and June 2014. By taking full history on admission, laboratory workup including HCV Ab, echocardiography study, and coronary angiography, we calculated the mean number of coronary artery lesions and the mean number of affected coronary artery vessels for all patients. The severity of the coronary lesions was estimated using the Gensini score. Results. HCV seropositive patients referred for coronary angiography were about 30.3% (which is greater than the prevalence of HCV seropositivity among general population in Egypt), patients proved to have CAD who are HCV antibody positive had more severe coronary lesions than in seronegative one (p<0.05), and patients proved to have CAD who are HCV antibody positive had comparable prevalence of cardiovascular risk factors as seronegative patients except for diabetes and hypertension which are more prevalent in seronegative patients (p<0.05). Conclusion. Prevalence of HCV antibody positive patients referred for coronary angiography was about 30.3%, and CAD patients who are HCV antibody positive had more severe coronary lesions and less prevalence of diabetes and hypertension than HCV antibody negative.
MicroRNAs in Coronary Heart Disease: Ready to Enter the Clinical Arena?
Authors: Cavarretta Elena , Frati Giacomo
Published: November 2016

Coronary artery disease (CAD) and its complication remain the leading cause of mortality in industrialized countries despite great advances in terms of diagnosis, prognosis, and treatment options. MicroRNAs (miRNAs), small noncoding RNAs, act as posttranscriptional gene expression modulators and have been implicated as key regulators in several physiological and pathological processes linked to CAD. Circulating miRNAs have been evaluated as promising novel biomarkers of CAD, acute coronary syndromes, and acute myocardial infarction, with prognostic implications. Several challenges related to technical aspects, miRNAs normalization, drugs interaction, and quality reporting of statistical multivariable analysis of the miRNAs observational studies remain unresolved. MicroRNA-based therapies in cardiovascular diseases are not ready yet for human trials but definitely appealing. Through this review we will provide clinicians with a concise overview of the pros and cons of microRNAs.
Pediatric Isolated Sinonasal Schwannoma: A New Case Report and Literature Review
Authors: Ma Xiao-Hui , Zhou Hai-Chun , Lai Can , Zhu Kun , Jia Xuan
Published: November 2016

Schwannomas of the paranasal sinus are uncommon. Less than 4% of schwannomas involve the nasal cavity and paranasal sinuses, even less in the pediatric age group. A case of schwannoma arising in maxillary sinus in a 2.5-year-old Chinese boy is reported. The basis for discussion of this case is the exceptional rarity of sinonasal schwannoma in pediatric patients.
Bilateral Numb Chin Syndrome as the Initial Presentation of Burkitt’s Lymphoma/Leukemia: A Report of Two Cases and Review of the Literature
Authors: Algahtani Hussein , Shirah Bader , Bassuni Wafaa , Adas Reem
Published: November 2016

Numb chin syndrome, also known as mental nerve neuropathy, is a rare sensory neuropathy characterized by paresthesia and hypoesthesia in the area supplied by the mental nerve and its branches. This syndrome may be the first symptom of underlying malignancy or the first sign of recurrence and metastasis in patients with preexisting cancer. In this article, we present two cases with bilateral numb chin syndrome as the first manifestation of Burkitt’s lymphoma/leukemia and review the relevant literature. Numb chin syndrome should be considered as a warning sign and raise the suspicion for an underlying malignancy. Bilateral involvement is especially hazardous and must not be underestimated. In fact, an astute neurologist and internist who realizes that chin numbness is a potentially significant symptom can then exclude serious underlying malignancies. Standard diagnostic protocol with different modalities of imaging based on the availability and experience of the radiology team should be mandatory. High index of suspicion should be practiced to avoid delay in diagnosis and progression of the underlying malignancy.
Surviving All Odds: A Unique Case of Multiple Congenital Unruptured Sinus of Valsalva Aneurysms Involving Both Left and Right Coronary Sinuses with Biventricular Dysfunction and Heart Block
Authors: Vijay B Aniketh , Vijan Vikrant , Mathew Navin
Published: November 2016

Aneurysms of the sinus of Valsalva are very uncommon, with an incidence ranging from 0.1 to 3.5% of all congenital heart defects. Very few cases have been reported in the literature that presented with involvement of two or more sinuses. We report a case of 27-year-old male with a history of exertional breathlessness of one-month duration. After complete evaluation using transesophageal echocardiography (TEE) and multiple detector computed tomography (MDCT) scanning, the patient was diagnosed to have large congenital unruptured sinus of Valsalva aneurysms involving both left and right coronary sinuses with extension into the interventricular septum. The patient also displayed second-degree heart block (Mobitz type 2) and biventricular dysfunction. The patient was managed successfully. We present the case with an aim to highlight the management challenges including intraoperative and postoperative complications that are associated with unruptured sinus of Valsalva aneurysms of ≥2 sinuses.
Candida glabrata Pneumonia in a Patient with Chronic Obstructive Pulmonary Disease
Authors: Yazici Onur , Cortuk Mustafa , Casim Hasan , Cetinkaya Erdogan , Mert Ali , Benli Ali Ramazan
Published: November 2016

Pneumonia remains an important cause of morbidity and mortality among infectious diseases. Streptococcus pneumoniae and viruses are the most common cause of pneumonia. Candidiasis in such patients has been associated with haemodialysis, fungal colonization, exposure to broad-spectrum antibiotics, intensive care unit (ICU) hospitalization, and immunocompromised patients. The most common cause of infection is C. albicans. The case presented here is of a 66-year-old male patient diagnosed with C. glabrata. The patient suffered from chronic obstructive pulmonary disease.
Ventricular Fibrillation-Induced Cardiac Arrest Results in Regional Cardiac Injury Preferentially in Left Anterior Descending Coronary Artery Territory in Piglet Model
Authors: Venkata Giridhar Kaliki , Forder John R. , Clark Dan , Shih Andre , Udassi Sharda , Badugu Srinivasarao , Lamb Melissa A. , Porvasnik Stacy L. , Shih Renata S. , Colon-Lopez Dalia , Zaritsky Arno L. , Haque Ikram U. , Udassi Jai P.
Published: November 2016

Objective. Decreased cardiac function after resuscitation from cardiac arrest (CA) results from global ischemia of the myocardium. In the evolution of postarrest myocardial dysfunction, preferential involvement of any coronary arterial territory is not known. We hypothesized that there is no preferential involvement of any coronary artery during electrical induced ventricular fibrillation (VF) in piglet model. Design. Prospective, randomized controlled study. Methods. 12 piglets were randomized to baseline and electrical induced VF. After 5 min, the animals were resuscitated according to AHA PALS guidelines. After return of spontaneous circulation (ROSC), animals were observed for an additional 4 hours prior to cardiac MRI. Data (mean ± SD) was analyzed using unpaired t-test; p value ≤ 0.05 was considered statistically significant. Results. Segmental wall motion (mm; baseline versus postarrest group) in segment 7 (left anterior descending (LAD)) was 4.68±0.54 versus 3.31±0.64, p=0.0026. In segment 13, it was 3.82±0.96 versus 2.58±0.82, p=0.02. In segment 14, it was 2.42±0.44 versus 1.29±0.99, p=0.028. Conclusion. Postarrest myocardial dysfunction resulted in segmental wall motion defects in the LAD territory. There were no perfusion defects in the involved segments.
Ex Vivo Area-Metric Analysis of Root Canal Obturation Using Cold and Warm Gutta-Percha
Authors: Olczak Katarzyna , Klimek Leszek , Pawlicka Halina
Published: November 2016

Purpose. To evaluate the percentage content of gutta-percha, sealer, and voids in a filled canal area following three different filling techniques, using microphotographs and Nis Elements® software. Material and Methods. After completing chemomechanical preparation, the teeth (n=48) were randomly divided into three groups (n=16) and filled by either cold lateral condensation (CLC group), the continuous wave technique (EOU group), and the ProTaper® thermoplasticized obturator (PT group). The roots were then sectioned horizontally 2.5, 6.5 and 8.5 mm from the tooth apical foramen. The surface areas of the sealer, voids, and gutta-percha (PGFA percentage of gutta-percha-filled area) were calculated and the results subjected to statistical analysis (Kruskal-Wallis test). Results. The percentage of gutta-percha (PGFA) was lower in the apical third of the canal for the CLC and EOU groups than the PT group. In the middle and the coronal third of the canal, the PGFA value was higher after using thermal techniques (EOU and PT) than cold lateral condensation (CLC). The presence of voids was comparable in the fillings performed using warm and cold gutta-percha obturation at all levels. Conclusion. Although thermal methods of root canal obturation allow higher PGFA values to be obtained than cold lateral condensation, the content of voids is comparable.
Fault Diagnosis Method on Polyvinyl Chloride Polymerization Process Based on Dynamic Kernel Principal Component and Fisher Discriminant Analysis Method
Authors: Gao Shu-zhi , Wu Xiao-feng , Wang Gui-cheng , Wang Jie-sheng , Chai Zi-qing
Published: November 2016

In view of the fact that the production process of Polyvinyl chloride (PVC) polymerization has more fault types and its type is complex, a fault diagnosis algorithm based on the hybrid Dynamic Kernel Principal Component Analysis-Fisher Discriminant Analysis (DKPCA-FDA) method is proposed in this paper. Kernel principal component analysis and Dynamic Kernel Principal Component Analysis are used for fault diagnosis of Polyvinyl chloride (PVC) polymerization process, while Fisher Discriminant Analysis (FDA) method was adopted to make failure data for further separation. The simulation results show that the Dynamic Kernel Principal Component Analyses to fault diagnosis of Polyvinyl chloride (PVC) polymerization process have better diagnostic accuracy, the Fisher Discriminant Analysis (FDA) can further realize the fault isolation, and the actual fault in the process of Polyvinyl chloride (PVC) polymerization production can be monitored by Dynamic Kernel Principal Component Analysis.
A Comparative Performance Evaluation of Some Novel “Green” and Traditional Antiscalants in Calcium Sulfate Scaling
Authors: Popov Konstantin , Rudakova Galina , Larchenko Vladimir , Tusheva Mariya , Kamagurov Semen , Dikareva Julia , Kovaleva Natalya
Published: November 2016

A relative ability of industrial samples of four phosphorus-free polymers (polyaspartate (PASP); polyepoxysuccinate (PESA); polyacrylic acid sodium salt (PAAS); copolymer of maleic and acrylic acid (MA-AA)) and of three phosphonates (aminotris(methylenephosphonic acid), ATMP; 1-hydroxyethane-1,1-bis(phosphonic acid), HEDP; phosphonobutane-1,2,4-tricarboxylic acid, PBTC) to inhibit calcium sulfate precipitation is studied following the NACE Standard along with dynamic light scattering (DLS), scanning electron microscopy (SEM), and X-ray diffraction (XRD) technique. For the 0.5 mg·dm−3dosage, the following efficiency ranking was found:MA-AA~ATMP>PESA (400–1500 Da)>PASP (1000–5000 Da)≫PAAS (3000–5000 Da)~PBTC~HEDP. The isolated crystals are identified as gypsum. SEM images for PESA, PASP, PAAS, and HEDP and for a blank sample indicated the needle-like crystal morphology. Surprisingly, the least effective reagent PBTC revealed quite a different behavior, changing the morphology of gypsum crystals to an irregular shape. The DLS experiments exhibited a formation of 300 to 700 nm diameter particles with negativeζ-potential around −2 mV for all reagents.Although suchζ-potential values are not capable of providing colloidal stability, all three phosphonates demonstrate significant gypsum particles stabilization relative to a blank experiment.
Transformation Groups for a Schwarzschild-Type Geometry in f(R) Gravity
Authors: Dil Emre , Zafer Talha
Published: November 2016

We know that the Lorentz transformations are special relativistic coordinate transformations between inertial frames. What happens if we would like to find the coordinate transformations between noninertial reference frames? Noninertial frames are known to be accelerated frames with respect to an inertial frame. Therefore these should be considered in the framework of general relativity or its modified versions. We assume that the inertial frames are flat space-times and noninertial frames are curved space-times; then we investigate the deformation and coordinate transformation groups between a flat space-time and a curved space-time which is curved by a Schwarzschild-type black hole, in the framework of f(R) gravity. We firstly study the deformation transformation groups by relating the metrics of the flat and curved space-times in spherical coordinates; after the deformation transformations we concentrate on the coordinate transformations. Later on, we investigate the same deformation and coordinate transformations in Cartesian coordinates. Finally we obtain two different sets of transformation groups for the spherical and Cartesian coordinates.
Myoinositol and D-Chiro Inositol in Improving Insulin Resistance in Obese Male Children: Preliminary Data
Authors: Mancini Mario , Andreassi Alice , Salvioni Michela , Pelliccione Fiore , Mantellassi Gianna , Banderali Giuseppe
Published: November 2016

Myoinositol and D-chiro inositol, which are inositol isomers, have been shown to possess insulin-mimetic properties and to improve insulin resistance, especially in women with polycystic ovary syndrome. However, it has not been determined if this relationship exists also in children. Based on these previous findings, we hypothesized that inositol could be effective in improving insulin sensitivity in children with insulin resistance. To evaluate this hypothesis, we administered both inositol formulations before carrying out an oral glucose tolerance test (OGTT) in a group of obese insulin-resistant male children with high basal insulin levels and compared the values obtained with an OGTT previously conducted without inositol, in the same group, with unchanged BMI. Our results confirm that myoinositol and D-chiro inositol acutely reduce insulin increase after glucose intake mainly in children with high basal insulin level.
Large-Scale Experimental and Numerical Study of Blast Acceleration Created by Close-In Buried Explosion on Underground Tunnel Lining
Authors: Soheyli Mohamad Reza , Akhaveissy A. H. , Mirhosseini S. M.
Published: November 2016

Despite growing demands for structures in water transportation tunnels, underground installations, subsurface dams, and subterranean channels, there is limited field knowledge about the dynamic behavior of these structures in the face of near-fault earthquakes or impulse excitations. This study conducted a large-scale test on underground tunnel excited by two close-in subsurface explosions. The horizontal and vertical acceleration were recorded on the vertical wall of the tunnel and the free field data including the acceleration on the ground surface at 11-meter distance from the tunnel. The frequency domain analysis of recorded results determined the frequency 961 Hz and 968 Hz for 1.69 kg and 2.76 kg equivalent T.N.T., respectively. Then, finite element analysis results were compared with the test data. The comparisons demonstrated a good correlation and satisfied the field data. Finally, based on numerical modeling, a parametric study was applied to determine the effects of shear wave velocity distance of the crater with respect to the tunnel on impulse response of the tunnel.
The Role of Hydrogen Bonding on Laminar Burning Velocity of Hydrous and Anhydrous Ethanol Fuel with Small Addition of n-Heptane
Authors: Suarta I Made , Wardana I. N. G. , Hamidi Nurkholis , Wijayanti Widya
Published: November 2016

The molecular structure of mixed hydrous and anhydrous ethanol with up to 10% v n-heptane had been studied. The burning velocity was examined in a cylindrical explosion combustion chamber. The result showed that the burning velocity of hydrous ethanol is higher than anhydrous ethanol and n-heptane at stoichiometric, rich, and very rich mixtures. The burning velocity of hydrous ethanol with n-heptane drops drastically compared to the burning velocity of anhydrous ethanol with n-heptane. It is caused by two reasons. Firstly, there was a composition change of azeotropic hydrous ethanol molecules within the mixture of fuel. Secondly, at the same volume the number of ethanol molecules in hydrous ethanol was less than in anhydrous ethanol at the same composition of the n-heptane in the mixture. At the mixture of anhydrous ethanol with n-heptane, the burning velocity decreases proportionally to the addition of the n-heptane composition. The burning velocity is between the velocities of anhydrous ethanol and n-heptane. It shows that the burning velocity of anhydrous ethanol mixed with n-heptane is only influenced by the mixture composition.
Standard versus Abdominal Lifting and Compression CPR
Authors: Zhang Sisen , Liu Qing , Han Shupeng , Zhang Ziran , Zhang Yan , Liu Yahua , Li Jing , Wang Lixiang
Published: November 2016

Background. This study compared outcomes of abdominal lifting and compression cardiopulmonary resuscitation (ALP‐CPR) with standard CPR (STD‐CPR). Materials and Methods. Patients with cardiac arrest seen from April to December 2014 were randomized to receive standard CPR or ALP‐CPR performed with a novel abdominal lifting/compression device. The primary outcome was return of spontaneous circulation (ROSC). Results. Patients were randomized to receive ALP‐CPR (n = 40) and STD‐CPR (n = 43), and the groups had similar baseline characteristics. After CPR, 9 (22.5%) and 7 (16.3%) patients in the ALP‐CPR and STD‐CPR groups, respectively, obtained ROSC. At 60 minutes after ROSC, 7 (77.8%) and 2 (28.6%) patients, respectively, in the ALP‐CPR and STD‐CPR groups survived (P = 0.049). Patients in the ALP‐CPR group had a significantly higher heart rate and lower mean arterial pressure (MAP) than those in the STD‐CPR group (heart rate: 106.8 versus 79.0, P < 0.001; MAP: 60.0 versus 67.3 mm Hg, P = 0.003). The posttreatment PCO2 was significantly lower in ALP‐CPR group than in STD‐CPR group (52.33 versus 58.81, P = 0.009). PO2 was significantly increased after ALP‐CPR (45.15 to 60.68, P < 0.001), but it was not changed after STD‐CPR. PO2 after CPR was significantly higher in the ALP‐CPR group (60.68 versus 44.47, P < 0.001). There were no differences between genders and for patients who are > 65 or ≤ 65 years of age. Conclusions. The abdominal lifting and compression cardiopulmonary resuscitation device used in this study is associated with a higher survival rate after ROSC than standard CPR.
New Exponential Stability Results for Neutral Stochastic Systems with Distributed Delays
Authors: Wang Jian
Published: November 2016

This paper studies the stability problem of a grey neutral stochastic system with distributed delays. The main feature of a grey system is that the parameters of system are evaluated by grey numbers, and system has the strong background in engineering applications. However, the literature dealing with the stability problem for grey system seems to be scarce. The main aim of this paper is to fill the gap. Based on the Lyapunov stability theorem and Itô’s formula, especially, using the decomposition technique of the continuous matrix-covered sets of grey matrix, we propose several novel sufficient conditions, which ensure our considered grey system in mean-square exponential stability and almost surely exponential stability. Furthermore, two examples are provided to show the effectiveness of the obtained results.
Abstract A013: Favorable changes in tumor microenvironment following intravenous dosing with live attenuated Listeria monocytogenes-based immunotherapy
Authors: Deng Weiwen , Tsujikawa Takahiro , Nair Nitya , Hudson Thomas , Liu Weiqun , Rae Chris S. , Lemmens Edward E. , Desbien Anthony W. , Hanson William , Lauer Peter , Coussens Lisa M. , Brockstedt Dirk G. , Dubensky Thomas W. , Leong Meredith L.
Published: November 2016

Modification of the tumor microenvironment (TME) to promote immune-mediated tumor cell destruction is considered to be an essential step for effective immunotherapy. We are evaluating recombinant live-attenuated, double deleted Listeria monocytogenes (LADD) as an immunotherapy platform for the treatment of cancer in several clinical trials in diverse indications. One LADD strain, known as CRS-207, has been engineered to express the tumor-associated antigen mesothelin and is being tested in pancreatic, ovarian and mesothelioma malignancies. Using multi-dimensional immunohistochemistry of paired biopsies from three patients with mesothelioma, we demonstrate the recruitment and expansion of effector tumor-infiltrating lymphocytes, including CD8+ T cells, mature DCs, CD163− macrophages and NK cells, following two prime infusions of CRS-207. In several different syngeneic mouse tumor models, we demonstrate that treatment with LADD engineered to express endogenous tumor antigens also induced significant changes in the TME that were consistent with changes observed in cancer patients, including enhanced CD8+ T cell effector function, recruitment of critical antigen presenting cells and reduction of regulatory T cells, and these changes correlated with significant therapeutic benefit in the mouse. LADD-induced changes to the TME were required for synergistic therapeutic antitumor efficacy combined with immune checkpoint blockade, including targeting MC38 tumor-specific neoantigens. Together, these findings demonstrate that intravenous administration of recombinant LADD therapy induces favorable changes in the tumor microenvironment in mice and humans with promise for effective outcomes in human clinical trials.

Citation Format: Weiwen Deng, Takahiro Tsujikawa, Nitya Nair, Thomas Hudson, Weiqun Liu, Chris S. Rae, Edward E. Lemmens, Anthony W. Desbien, William Hanson, Peter Lauer, Lisa M. Coussens, Dirk G. Brockstedt, Thomas W. Dubensky, Jr., Meredith L. Leong. Favorable changes in tumor microenvironment following intravenous dosing with live attenuated Listeria monocytogenes-based immunotherapy [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A013.
Abstract A025: Association of functionally distinct ERAP1 variants in HPV positive cancer
Authors: Reeves Emma , King Emma , Elliott Tim , Thomas Gareth , James Edward
Published: November 2016

Human papillomavirus (HPV) infection accounts for 5% cancers worldwide, with cervical carcinoma and squamous cell carcinoma of the head and neck (SCCHN) being most common. HPV can enable immune evasion, with 50% of HPV+ SCCHN having reduced pMHC I expression, correlating with fewer tumor infiltrating lymphocytes (TIL) and a worse clinical outcome. Polymorphisms in the endoplasmic reticulum aminopeptidase1 (ERAP1), a key component of antigen processing, trimming N-terminally extended peptides for MHC I, are associated with prognosis and outcome in cervical carcinoma. We have previously demonstrated ERAP1 to be highly polymorphic, forming distinct allotypes with functional differences. Here we investigate the contribution of ERAP1 in the pathogenesis of SCCHN. We identified a number of novel ERAP1 allotype pairs (both chromosomal copies) from an HPV+ SCCHN cohort. Assessment of trimming function revealed a range of abilities to generate the model epitope SIINFEHL from individual amino acid or AIVMK precursors. Furthermore, the ability to generate HPV-16 E6/E7 specific epitopes also demonstrated varying trimming phenotypes. Interestingly, the overall ability to generate the final epitopes (model and HPV) in TILLOW patients was poor, whereas TILHIGH patients were able to generate these epitopes efficiently. This reveals ERAP1 gene sequence and function stratifies with TIL levels and prognosis, suggesting that the successful presentation of HPV-16 E6/E7 epitopes at the cell surface depends on the ERAP1 allotype pairs expressed within an individual. Furthermore, the allotype pairs correlate with levels of tumor infiltrate, suggesting ERAP1 activity as an indicator of prognosis in HPV+ SCCHN patients.

Citation Format: Emma Reeves, Emma King, Tim Elliott, Gareth Thomas, Edward James. Association of functionally distinct ERAP1 variants in HPV positive cancer [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A025.
Abstract A037: The Agenus Immunogenic Mutation platform (AIM™) generates synthesis-ready blueprints for the AutoSynVax™ vaccine patient-specific neo-antigen vaccine
Authors: Uduman Mohamed , Karapetyan Armen , Khattar Mithun , Tanne Antoine , Morin Benjamin , Zelin Justin , Craig Sandra , Shiwen Shiwen , Joshi Bishnu , Findeis Mark A. , Wilson Nicholas , Drouin Elise , Yang Amy , Raizer Jeffrey , Goldberg John , Buell Jennifer , Stein Robert , Castle John , Levey Daniel L.
Published: November 2016

Agenus is clinically testing Prophage™, an individualized tumor vaccine which uses heat-shock proteins endogenously complexed to neo-antigens harvested from the patient's own tumor. Agenus' genomics and bioinformatics unit rapidly identifies potentially immunogenic neo-antigens in the patient's tumor for use in immunomonitoring. However, in cases such as when the tumor mass is insufficient to generate the Prophage vaccine, we plan to treat patients with an individualized synthetic neo-antigen vaccine, AutoSynVax™ vaccine, combined with QS21 Stimulon® adjuvant and optionally immunomodulatory antibodies. In a murine model, we have demonstrated tumor control after treatment with our synthetic vaccine.

The majority of mutations in human tumors are unique to the individual tumor, necessitating the rapid identification of mutations using next generation sequencing and bioinformatics. Further, the number of candidate immunogens presented on a tumor can range from a handful to hundreds. Accurately identifying tumor mutations; determining their impact, expression and translation; and predicting ability to bind patient-specific HLA class I and II molecules and elicit an immune response (immunogenicity) is complex, particularly in the context of clinical trials.

The AutoSynVax™ vaccine platform leverages AIM™, the Agenus Immunogenic Mutation workflow, to generate a synthesis-ready blueprint for optimal immunogenic patient-specific neo-antigen vaccines. AIM™ comprises a robust and efficient approach to computational vaccinology designed to generate an immunogenic candidate blueprint, agnostic to vaccine format, followed by a format-specific blueprint ready for vaccine synthesis and manufacture.

Citation Format: Mohamed Uduman, Armen Karapetyan, Mithun Khattar, Antoine Tanne, Benjamin Morin, Justin Zelin, Sandra Craig, Shiwen Shiwen, Bishnu Joshi, Mark A. Findeis, Nicholas Wilson, Elise Drouin, Amy Yang, Jeffrey Raizer, John Goldberg, Jennifer Buell, Robert Stein, John Castle, Daniel L. Levey. The Agenus Immunogenic Mutation platform (AIM™) generates synthesis-ready blueprints for the AutoSynVax™ vaccine patient-specific neo-antigen vaccine [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A037.
Abstract A038: Oncolytic virotherapy combination with DC-based immunotherapy for the treatment of melanoma
Authors: Banki Zoltan , Koske Iris , Barnstorf Isabel , Tripp Christoph , Stoitzner Patrizia , Romani Nikolaus , Wollmann Guido , Kimpel Janine , Laer Dorothee Holm-von
Published: November 2016

VSV-GP, a novel chimeric Vesicular Stomatitis Virus (VSV) pseudotyped with the glycoprotein of the lymphocytic choriomeningitis virus represents a promising oncolytic virus (OV) that preferentially targets and kills cancer cells. Release of tumor antigens and activation of immune response by OV therapy might support dendritic cell (DC)-mediated anti-tumor immunity. Thus in our study we analyzed the efficacy and immune mechanisms of the combination of VSV-GP oncolytic virotherapy with DC-based immunotherapy. Combination of VSV-GP therapy and DC-based vaccination was investigated in the syngeneic subcutaneous B16-OVA melanoma model. SIINFEKL-loaded CpG-activated DCs (DCVacc) and VSV-GP were applied intra- and peritumorally and immune responses were analyzed in the spleen and tumor tissues. The DCVacc/VSV-GP combination therapy resulted in a significantly improved survival compared to single treatments. Surviving mice from the DCVacc/VSV-GP treated group showed a long lasting anti-tumor immunity against B16-OVA and partial anti-tumor immunity against non-OVA B16 melanoma in rechallenge experiments. Analyzing specific cytotoxic T lymphocyte (CTL) responses induced by DCVacc and VSV-GP single and combination treatments we found that both DCVacc and DCVacc/VSV-GP induced comparable levels of OVA-specific CD8+ T cell responses. In addition a strong VSV N peptide-specific CD8+ T cell response was found upon VSV-GP and DCVacc/VSV-GP treatments. The improved therapeutic effect by the DCVacc/VSV-GP combination treatment correlated with increased numbers of tumor infiltrating lymphocytes (TIL) and elevated Tconv/Treg and CD8+/Treg ratios. Furthermore, depletion of CD8+ T cells but not NK cells abrogated the therapeutic effect of DCVacc/VSV-GP. Taken together, the combination of VSV-GP and DC-based immunotherapy might represent a promising therapeutic option for the treatment of melanoma.

Citation Format: Zoltan Banki, Iris Koske, Isabel Barnstorf, Christoph Tripp, Patrizia Stoitzner, Nikolaus Romani, Guido Wollmann, Janine Kimpel, Dorothee Holm-von Laer. Oncolytic virotherapy combination with DC-based immunotherapy for the treatment of melanoma [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A038.
Abstract A046: Identification and validation of HCC-specific gene transcriptional signature for tumor antigen discovery
Authors: Petrizzo Annacarmen , Caruso Francesca P. , Tagliamonte Maria , Tornesello Maria Lina , Ceccarelli Michele , Costa Valerio , Aprile Marianna , Esposito Roberta , Ciliberto Gennaro , Buonaguro Franco M. , Buonaguro Luigi
Published: November 2016

A novel two-step bioinformatics strategy was applied for identification of signatures with therapeutic implications in hepatitis-associated HCC. Transcriptional profiles from HBV- and HCV-associated HCC samples were compared with normal liver tissue controls. Resulting HCC modulated genes were subsequently compared with different normal tissue samples. Two related signatures were identified, namely “HCC-associated” and “HCC-specific.” Expression data were validated by RNA-Seq analysis carried out on unrelated HCC samples and protein expression was confirmed according to the publicly available database at http://www.proteinatlas.org/. Among all, only two proteins (namely AKR1B10 and IGF2BP3) were found strictly HCC-specific with no expression in 18/20 normal tissues. Target peptides for vaccine design were predicted for both proteins associated with the most prevalent HLA-class I and II alleles. The described novel strategy showed to be feasible for identification of HCC-specific proteins as highly potential target for HCC immunotherapy (Petrizzo et al., Scientific Reports, in press).

Citation Format: Annacarmen Petrizzo, Francesca P. Caruso, Maria Tagliamonte, Maria Lina Tornesello, Michele Ceccarelli, Valerio Costa, Marianna Aprile, Roberta Esposito, Gennaro Ciliberto, Franco M. Buonaguro, Luigi Buonaguro. Identification and validation of HCC-specific gene transcriptional signature for tumor antigen discovery [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A046.
Abstract A053: Targeting ICOS improves immune-mediated control of tumor growth in humanized mice
Authors: Burlion Aude , Corneau Aurélien , Marodon Gilles
Published: November 2016

Checkpoint blockade inhibitors are the most promising and effective strategy for T-cell mediated cancer immunotherapy of the past 20 years. Part of the anti-tumoral effect of these checkpoint inhibitors might be due to preferential targeting of regulatory T cells (Treg), essential for immune homeostasis. Here, we investigated whether the reported higher expression of ICOS on Treg than on regular T cells might be used as a flag to target human Treg to improve tumor-directed immune response. We report that a novel murine anti-human ICOS IgG1 mAb preferentially depleted Treg in NSG mice reconstituted with a human immune system from cord blood CD34+ cells, leading to an increased CD8 to Treg ratio. However, this was insufficient to affect growth of the breast cancer cell line MDA-MB-231 in humanized mice. We thus administered low dose cyclophosphamide that only moderately affected tumor growth to induce immunogenic cell death and improve tumor infiltration by human cells. Treatment of humanized mice with a combination of cyclophosphamide and the anti-ICOS mAb led to a marked reduction in tumor growth. Using mass cytometry (Cytof), we then analyzed the expression of 29 markers to quantify the main human and murine cell subsets in the tumor. We observed higher activation of CD8+ T cells in the combined-treatment group as judged by their higher expression of CD45RO and HLA-DR, relative to chemotherapy alone. Accordingly, depletion of CD8+ T cells with a mAb partly abolished the therapeutic effect of the combination, showing that these cells participated in tumor rejection. Notably, we also observed improved infiltration of human monocytes, human plasmacytoid dendritic cells and murine CD11b+CD11c+ cells in the tumor, suggesting that part of the effect of the combination therapy on tumor growth might proceed through these subsets. Altogether, our results demonstrate that ICOS, through its effect on regulatory T cells, release a brake in the immune response to tumors in humanized mice, and as such might be considered as a novel immune checkpoint inhibitor.>

Note: This abstract was not presented at the conference.

Citation Format: Aude Burlion, Aurélien Corneau, Gilles Marodon. Targeting ICOS improves immune-mediated control of tumor growth in humanized mice [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A053.
Abstract A059: Combinatorial proteomic analysis of the receptor programmed cell death (PD)-1 uncovers new checkpoint modulators
Authors: Peled Michael , Mor Adam
Published: November 2016

Programmed cell death (PD)-1 is one of the most important inhibitory checkpoints in T cells. Antibodies targeting PD-1 have elicited durable clinical responses in multiple tumor types and long-term remissions in some. Nevertheless, response to anti-PD-1 approaches is limited to a small fraction of patients and thus, a more complete understanding of this pathway should provide i) novel biomarkers for potential responders and ii) potential new therapeutic targets for refractory patients. We took an unbiased approach, exploiting high-resolution mass spectrometry, to uncover novel proteins that either interact with the cytoplasmic tail of PD-1 or are dephosphorylated downstream of the PD-1. We identified almost 20 proteins that interacted directly with the tail of PD-1, and approximately 100 proteins that their phosphorylation status was changed upon PD-1 signaling. Two of the more abundant proteins, EFHD2 and SH2D1A, were functionally analyzed for their contribution in mediating PD-1 inhibitory responses. Silencing EFHD2 resulted in abrogation of PD-1 inhibitory effect, including elimination of the ability of PD-1 signaling to inhibit cytokine secretion, cell proliferation, and cellular adhesion. Mechanistically, EFHD2 co-localized with PD-1 in the immunologic synapse, and was necessary for PD-1 clustering. In contrast, silencing SH2D1A augmented PD-1 function while over-expression of the same protein blocked PD-1 effects. We than discovered that SH2D1A physically competed with the phosphatase SHP2 for the same binding site on the tail of PD-1. Studying PD-1 interactome and phosphoproteome has thus identified new proteins that can modulate PD-1 function in opposite ways. These proteins should be further explored as potential targets in cancer.

Citation Format: Michael Peled, Adam Mor. Combinatorial proteomic analysis of the receptor programmed cell death (PD)-1 uncovers new checkpoint modulators [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A059.