bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Security Uncertainty and Demand for Retirement Saving
Authors: Jappelli Tullio , Marino Immacolata , Padula Mario
Published: December 2020

The life‐cycle model predicts an association between increased demand for retirement saving and the level of expected future social security benefits. The precautionary saving model shows that the risk associated to future benefits also matters. If social security benefits become more uncertain, individuals should react by increasing their demand for retirement saving. To assess the empirical relevance of this mechanism, we relate individual level measures of social security risk to demand for retirement saving vehicles. Using the Bank of Italy Survey of Household Income and Wealth, we find higher participation in private pension funds among individuals who expect lower and more uncertain social security benefits.
Reproductive Coercion among Intimate Partner Violence Survivors in Nairobi
Authors: Wood Shannon N. , Kennedy S. Rachel , Akumu Irene , Tallam Catherine , Asira Ben , Hameeduddin Zaynab , McGready John , Zimmerman Linnea A. , Kennedy Caitlin E. , Glass Nancy , Decker Michele R.
Published: December 2020

Reproductive coercion (RC), or partner interference in reproductive decisions, limits women's autonomy. Little is known about RC behaviors and measurement in low‐ and middle‐income countries (LMICs). In this mixed‐methods study, we examined the transferability of the US‐developed RC Scale to the Kenyan context. Through community‐based sampling, recent intimate partner violence (IPV) survivors were recruited from Nairobi's informal settlements. We conducted quantitative analyses (n = 327) to assess the transferability of RC measures via exploratory factor analysis and used descriptive statistics to examine prevalence and continuous metrics. We conducted in‐depth interviews (IDIs; n = 30) to contextualize results. Psychometric analyses indicated a two‐factor solution comprising pregnancy coercion and condom manipulation (alpha = 0.86). Eighty‐two percent of IPV survivors reported experiencing RC (pregnancy coercion = 76.6 percent; condom manipulation = 59.5 percent). IDIs highlighted women's multiple, severe RC experiences; experiences described in IDIs were largely consistent with quantitative findings. We found the RC Scale was transferable to this LMIC context, where IPV survivors face prevalent, severe RC and would benefit from linkage to woman‐centered support services.
The role of 18F‐Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in assessment of complex invasive fungal disease and opportunistic co‐infections in patients with acute leukemia prior to allogeneic hematopoietic cell transplant
Authors: Longhitano Anthony , Alipour Ramin , Khot Amit , Bajel Ashish , Antippa Phillip , Slavin Monica , Thursky Karin
Published: December 2020

Introduction

Individuals diagnosed with acute lymphoid and myeloid malignancies are at significant risk of invasive fungal and bacterial infections secondary to their marked immunocompromised states with a significant high risk of mortality. The role of metabolic imaging with 18F‐Fluorodeoxyglucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) has been increasingly recognized in optimizing the diagnosis of invasive infection, monitoring the response to therapy and guiding the duration of antimicrobial therapy or need to escalate to surgical intervention.

Methods

Two distinct cases of pulmonary co‐infection of rare fungal and bacterial pathogens are explored in severely immunocompromised individuals where FDG PET/CT aided both patients to make a full recovery and transition to HCT. The first case explores mixed Scedosporium apiospermum and Rhizomucor pulmonary infection on a background of T cell/myeloid mixed phenotype acute leukemia ultimately warranting long‐term antifungal therapy and lobectomy prior to HCT. The second case explores Fusarium and Nocardia pulmonary infection on a background of relapsed AML also warranting surgical resection with lobectomy and long‐term antimicrobials prior to transition to HCT.

Discussion

The cases highlight the utility of FDG PET/CT to support the diagnosis of infections, including the presence or absence of disseminated infection, and to provide highly sensitive monitoring of the infection over time. FDG PET/CT played a key role in directing therapy duration decisions and prompted the necessity for surgical intervention. Ultimately, the use of FDG PET/CT allowed for a successful transition to HCT highlighting its value in this clinical setting.

Conclusion

FDG PET/CT has an emerging role in the diagnostic and monitoring pathway for complex infections in high‐risk immunocompromised patients.
Association between cerebrospinal fluid lactate concentration and central nervous system disease in dogs
Authors: Fitz Franziska R. , Reese Michael
Published: December 2020

Background

Cerebrospinal fluid (CSF) analysis is a sensitive tool for evaluating patients with neurologic diseases but is rarely specific. Biomarkers can be measured from any bodily fluid and can be useful indicators for the presence, severity, and prognosis of diseases.

Objectives

This study was designed to evaluate if CSF lactate can be used as a biomarker in dogs with central nervous system disease.

Methods

Peripheral venous blood and CSF were collected from 49 dogs with various intracranial diseases to evaluate correlations between blood and CSF lactate levels. Total nucleated cell count (TNCC) and CSF protein concentrations were also evaluated. All samples obtained were divided into normal (NG) and abnormal (AG) dogs based on a TNCC of ≤5 and >5 cells/μL and a protein concentration of ≤25 and >25 mg/dL, respectively. The AG dogs were further subdivided into those having <100 TNCCs/µL (AGL) and those having >100 TNCCs/µL (AGH). They were also subdivided into groups based on seizure activity (AGS), and inflammatory (AGI), or neoplastic diseases (AGN), and the respective lactate concentrations were then compared.

Results

Lactate concentrations were significantly increased in CSF and venous blood samples in the AG compared with the NG dogs, but no differences were found among the individual disease processes. In all dogs, CSF lactate concentrations were higher than venous blood lactate levels; however, no direct correlation between CSF and blood lactate concentrations was identified.

Conclusions

Cerebrospinal fluid lactate can be used as a biomarker in clinical settings as it can be measured via a commercially available lactometer immediately after collection without the need for special instrumentation or laboratory personnel.
Clinical consequences of the extremely rare anti‐PP1Pk isoantibodies in pregnancy: a case series and review of the literature
Authors: Di Ciaccio Pietro , Cutts Briony , Alahakoon Thushari Indika , Dennington Peta M. , Soo Luke A. , Curnow Jennifer
Published: December 2020

Background

The absence of the red cell antigens P, P1 and Pk, known as ‘p’, represents an extremely rare red cell phenotype. Individuals with this phenotype spontaneously form anti‐PP1Pk isoantibodies, associated with severe haemolytic transfusion reactions, recurrent spontaneous abortion and haemolytic disease of the fetus and newborn (HDFN).

Methods

We report a series of four successful pregnancies in three women with anti‐PP1Pk isoantibodies, one complicated by HDFN, another by intrauterine growth restriction, all managed supportively. We also review the literature regarding the management of pregnancy involving anti‐PP1Pk isoimmunization.

Results

The literature surrounding anti‐PP1Pk in pregnancy is limited to a very small number of case reports. The majority report management with therapeutic plasma exchange (TPE) with or without intravenous immunoglobulin. The relationship between titre and risk of pregnancy loss remains unclear, though a history of recurrent pregnancy loss appears important. Although a positive cord blood direct antiglobulin test is frequently noted, clinically significant HDFN appears uncommon, though possible.

Conclusion

Early initiation of TPE in high risk patients should be strongly considered. If possible, pregnancies should be managed in a high‐risk obstetric or maternal fetal medicine service. The fetus should be monitored closely with interval fetal ultrasound and middle cerebral artery peak systolic volume Doppler to screen for fetal anaemia. Timely sourcing of compatible blood products is likely to be highly challenging, and both directed and autologous donation should be contemplated where appropriate. The International Red Cell Donor Panel may also provide access to compatible products.
Two-Way Coupled Shooting Analysis of Fluid Force in the Annular Plain Seal and Vibration of the Rotor System
Authors: Kunori Yudai , Inoue Tsuyoshi , Miyake Kenjiro
Published: December 2020

In turbomachinery, the rotor dynamic (RD) fluid force generated in a fluid element, by the interaction between the shaft behavior and the fluid flow, is one of the causes of the shaft behavior and has a great influence on the stability of the turbomachinery. In order to improve the reliability of turbomachinery, it is important to analyze the dynamical behavior considering the mutual influence of the RD fluid force and shaft motion. In this paper, the two-way coupled analysis between the fluid force in the annular plain seal and the vibration of the rotor system was expanded by introducing the shooting method in it. The frequency response was obtained, and the onset speed of instability (OSI) was predicted effectively. The influence of parameters on the OSI was investigated and discussed. Then, the numerical results obtained by this two-way coupled shooting analysis was compared with the experimental results and the validity of the analysis was confirmed. The influence of disturbance on the error of predicted OSI was also discussed. The transition region to instability was introduced for the predicted OSI using the spectral radius, and the error between the numerical and experimental results of the OSI was explained. As a result, the two-way coupled shooting analysis can predict the OSI values in various situations of two-way coupled system more effectively than the direct numerical simulation. Also, the robustness of stability for the predicted OSI can be evaluated simultaneously by investigating the spectral radius and defining the transition region to instability appropriately.
Head-related transfer function recommendation based on perceptual similarities and anthropometric features
Authors: Pelzer Robert , Dinakaran Manoj , Brinkmann Fabian , Lepa Steffen , Grosche Peter , Weinzierl Stefan
Published: December 2020

Individualization of head-related transfer functions (HRTFs) can improve the quality of binaural applications with respect to the localization accuracy, coloration, and other aspects. Using anthropometric features (AFs) of the head, neck, and pinna for individualization is a promising approach to avoid elaborate acoustic measurements or numerical simulations. Previous studies on HRTF individualization analyzed the link between AFs and technical HRTF features. However, the perceptual relevance of specific errors might not always be clear. Hence, the effects of AFs on perceived perceptual qualities with respect to the overall difference, coloration, and localization error are directly explored. To this end, a listening test was conducted in which subjects rated differences between their own HRTF and a set of nonindividual HRTFs. Based on these data, a machine learning model was developed to predict the perceived differences using ratios of a subject's individual AFs and those of presented nonindividual AFs. Results show that perceived differences can be predicted well and the HRTFs recommended by the models provide a clear improvement over generic or randomly selected HRTFs. In addition, the most relevant AFs for the prediction of each type of error were determined. The developed models are available under a free cultural license.
Decision Outcomes in Sport: Influence of Type and Level of Stress
Authors: Hepler Teri J. , Andre Matt
Published: December 2020

In two experiments, the authors investigated the influence of stress type (i.e., low/no stress, mental, and physical), level (i.e., low, moderate, and high), and Type × Level interaction on intuitive decision frequency, decision quality, and decision speed. Participants were exposed to mental (i.e., color word task, mental arithmetic) and/or physical stress (i.e., running) and then required to make decisions regarding videotaped offensive situations in basketball. Intuitive decision frequency, decision quality, and decision speed were measured for each trial. Study 1 used a between-subjects design whereby 20 participants were randomly assigned to each of the five stress conditions. Results revealed that moderate stress was associated with faster decisions. Study 2 replicated the design and aim of Study 1 using a within-subject methodology (n = 42). Results suggested that moderate stress levels produced better, faster decisions. In conclusion, moderate levels of stress were associated with the most desirable decision outcomes.
Hotspot signatures at the North American passive margin
Authors: Tao Zhongmin , Li Aibing , Fischer Karen M.
Published: December 2020

The presence of localized low-velocity anomalies in the upper mantle beneath the passive Atlantic margin in North America is a puzzling geophysical observation. Whether the anomalies are caused by the remnant heat from past hotspots or ongoing asthenospheric upwelling is still debated. We addressed the formation of the anomalies based on a recent velocity model for eastern North America, which reveals new information on their shapes and anisotropic signatures. The low-velocity anomaly in New England appears as a narrow column above 90 km depth and broadens westward at depths of 120–200 km. Two slow anomalies are imaged under the central Appalachian Mountains between 140 km and 240 km. These low velocities correspond to pronounced positive radial anisotropy (Vsh > Vsv), indicating a dominantly horizontal asthenospheric flow. They also coincide with the tracks of the Great Meteor hotspot (140–115 Ma) and an inferred hidden hotspot (60–50 Ma). The anomalies in the central Appalachians could be due to lithospheric interaction with the second hotspot and subsequent lithospheric instabilities. The complex shape of the New England anomaly is consistent with interaction with both hotspots. The first hotspot could have eroded the base of the lithosphere, forming a channel, and the second hotspot could have further thinned the lithosphere and produced a localized cavity at shallow depths. Consequently, the indented lithosphere base would have filled with channelized asthenospheric flow or produced small-scale convection, helping to sustain the slow anomaly. Low-velocity anomalies at the North America passive margin are likely the consequences of prior hotspot interactions.
Mechanical contrast and asymmetric distribution of crustal deformation across plate boundaries: Insights from the northern Dead Sea fault system
Authors: Dembo Neta , Granot Roi , Hamiel Yariv
Published: December 2020

The distribution of permanent deformation near strike-slip plate boundaries and the underlying controlling variables are commonly poorly understood. Here we examine the crustal deformation across the northern Dead Sea fault system based on paleomagnetic observations and mechanical modeling. We focus our investigation on the region of the Lebanese restraining bend where the fault system strikes obliquely to the general Sinai-Arabia plate motion. We construct a series of crustal elasto-plastic models in which kinematics is based on geodetic measurements, and the geometry of the plate boundary is constrained by gravity data. Both the observed regional vertical axis rotations and the model results display significant counterclockwise rotations (as much as ∼50°) confined to the northern Sinai microplate located west of the bend. On the other hand, relatively minor rotations (<∼10°) are displayed for the adjacent Arabian plate. Our results, validated by structural evidence, suggest that the northern Sinai microplate is mechanically weaker than the adjacent crust of the Arabian plate. This mechanical contrast, along with the oblique convergence and change of slip rate along the Dead Sea fault system, is required to simulate the observed rotations. We propose that the crustal mechanical contrast across plate boundaries is a key parameter responsible for the distribution pattern of permanent vertical axis rotations.
Inconsistent effects of nitrogen canopy enrichment and soil warming on black spruce epiphytic phyllosphere bacterial communities, taxa, and functions
Authors: Khlifa Rim , Houle Daniel , Morin Hubert , Kembel Steven W.
Published: December 2020

Phyllosphere microbial communities have received considerable attention given their important influence on their plant hosts and on ecosystem functioning. In a context where climate change threatens the sustainability of ecosystems, it is important to understand how phyllosphere microbes will respond to changes in their environment. We used 16S rRNA gene amplicon sequencing to quantify phyllosphere bacterial communities of black spruce (Picea mariana (Mill.) B.S.P.) exposed to nitrogen canopy enrichment and soil warming in the boreal forest of Quebec, Canada. The treatments were applied from April to September 2015 and the sampling was done in September. Neither treatment influenced the overall community structure and diversity of black spruce phyllosphere bacterial communities. However, some bacterial taxa and inferred microbial functions did differ among treatments, revealing in particular a stronger response of some bacteria to soil warming rather than nitrogen enrichment. Our results suggest that soil warming could potentially induce more changes in phyllosphere bacterial taxa abundances and functions than could nitrogen addition, with potential consequences for microbial diversity and boreal forest ecosystem function under likely climate change scenarios. Our study suggests avenues for further research to integrate a more mechanistic understanding of the importance of phyllosphere microbes for black spruce and boreal forest ecosystems.
Measurement of D-meson production and flow in Pb–Pb collisions with ALICE at the LHC
Authors: Catalano Fabio
Published: December 2020

Open-charmed mesons are unique tools to study the properties of the Quark–Gluon Plasma (QGP) formed in ultra-relativistic nucleus–nucleus collisions. The nuclear modification factor ([Formula: see text]) and elliptic flow ([Formula: see text]) of [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] mesons were measured by the ALICE Collaboration in Pb–Pb collisions at [Formula: see text][Formula: see text]TeV. The D-meson [Formula: see text] provides information on the charm-quark interactions with the medium and the charm-quark energy loss. The D-meson elliptic flow at low transverse momentum ([Formula: see text]) gives insight into the participation of charm quarks in the collective expansion of the system and their possible in-medium thermalization. At high [Formula: see text], the [Formula: see text] is sensitive to the path-length dependence of parton energy loss. The role of the recombination mechanism is investigated measuring the [Formula: see text]-differential yield ratios between D-meson species with and without strange-quark content. Finally, the coupling of charm quarks to light quarks of the underlying medium is examined applying the Event-Shape Engineering (ESE) technique to the nonstrange D-meson elliptic flow.
On relations between principal eigenvalue and torsional rigidity
Authors: van den Berg Michiel , Buttazzo Giuseppe , Pratelli Aldo
Published: December 2020

We consider the problem of minimizing or maximizing the quantity [Formula: see text] on the class of open sets of prescribed Lebesgue measure. Here [Formula: see text] is fixed, [Formula: see text] denotes the first eigenvalue of the Dirichlet Laplacian on [Formula: see text], while [Formula: see text] is the torsional rigidity of [Formula: see text]. The optimization problem above is considered in the class of all domains [Formula: see text], in the class of convex domains [Formula: see text], and in the class of thin domains. The full Blaschke–Santaló diagram for [Formula: see text] and [Formula: see text] is obtained in dimension one, while for higher dimensions we provide some bounds.
Forest Trees as Naturally Available Seismic Metamaterials: Low Frequency Rayleigh Wave with Extremely Wide Bandgaps
Authors: Muhammad  , Wu Tingkai , Lim C. W.
Published: December 2020

This paper presents a comprehensive study and it concludes that the resonance of forest trees with properly aligned conditions precisely working as naturally available locally resonant metamaterials that are equipped with wonderful capability of generating low frequency extremely wide bandgaps in the earthquake frequency range of interest. At the geophysical scale, the propagation of Rayleigh wave in the soft sedimentary soil basin experiences strong wave attenuation when the longitudinal resonant modes of trees are coupled with vertical component of the Rayleigh wave that mimic wave hybridization phenomena. A finite element-based numerical technique is adopted and we considered a total of 10 cases where spacing, height, thickness and mechanical properties of resonant trees are varied to study the Rayleigh wave propagation and attenuation mechanism. The trapping and/or mode conversion of Rayleigh wave by resonant trees is observed as dominant phenomena for wave attenuation. A time history analysis is conducted based on an actual earthquake record to validate the performance and efficiency of the bandgaps. The effects of ground stiffness, resonant tree mechanical and geometric properties on the bandgaps are also discussed. The study explores another peculiar characteristic of the forest trees that controls the propagation of seismic wave to protect a region from earthquake hazards. Our study may motivate the relevant organizations, authorities and global communities on the needs of forestation to reduce the earthquake catastrophe.
Corruption Heterogeneity and Foreign Direct Investment
Authors: Le Tuan Viet
Published: December 2020

In this research, I study the relationship between bilateral Foreign Direct Investment (FDI) and difference in corruption between source and host countries. Using instrumental variables (IVs) approach, the results suggest that bilateral FDI between two countries might increase if the difference in corruption between them decreases. In addition, I find that firms from corrupt countries tend to invest abroad to exploit natural resources while those from less corrupt countries take advantage of relatively low local wages and open trade policies.
Marine dinocysts, acritarchs and less well-known NPP: tintinnids, ostracod and foraminiferal linings, copepod and worm remains
Authors: Mudie P. J. , Marret F. , Gurdebeke P. R. , Hartman J. D. , Reid P. C.
Published: December 2020

Nine non-pollen palynomorph (NPP) groups occur in Quaternary marine and brackish-water sediments; these groups represent various planktonic or micro- to macrobenthic organisms. Some extant NPP were previously classified as fossil Acritarcha, Chitinozoa or scolecodonts. We refer to reviews of these fossils and their applications for Paleozoic–Mesozoic biostratigraphy and palaeoecology but focus on extant marine NPP that can be studied by laboratory culture, genetics or micro-geochemical methods. Marine NPP include resting cysts of planktonic dinoflagellates and prasinophytes, tintinnids and other cilates, copepod eggs and skeletal remains, and various microzoobenthos: microforaminiferal organic linings, ostracod mandibles and carapace linings, various worm egg capsules and mouthparts. New micro-Fourier Transform Infrared spectroscopy spectra suggest the probable affinities of the tintinnid cyst type P and
Beringiella
. Our applications in marine biodiversity and provincialism studies emphasize under-studied polar regions and neglected ice-algae nano-plankton and compare climate-based NPP distributions to Ocean Biogeographic Information System realms. Trophic relationships are outlined using sediment-trap studies. Seasonal to annual-scale investigations of palaeoproduction provide new perspectives on ocean carbon budgets during times of rapid climate change and atmospheric carbon increase. More taxonomic and source-linkage studies of non-dinocyst marine NPP are needed but we outline potentials for studies of hemispheric or global-scale shifts in marine food webs as driven by ocean warming.
Authenticating Drivers Using Automotive Batteries
Authors: He Liang , Shu Yuanchao , Lee Youngmoon , Chen Dongyao , Shin Kang G.
Published: December 2020

Automakers have been improving, or even trying to replace, key-based driver authentication solutions, owing to their vulnerability to cyber attacks and single-point-of-failures, as well as their inability of driver identification. In line with this effort, we design a novel driver authentication system using automotive batteries, called Batteries-as-Authenticators (BAuth), to mitigate the limitations of key-based solutions by providing a second-factor authentication. BAuth is an add-on module installed between vehicles and their batteries, which uses the batteries as sensors to validate drivers' identities and actuators to enable/disable the cranking of vehicle's engine. We have prototyped and evaluated BAuth on 6 regular/hybrid/electric vehicles. Our evaluation shows BAuth to authenticate the drivers with a 98.17 (2.84)% averaged true (false) positive rates and tolerate the dynamics caused by the aging/temperature/state-of-charge of batteries. Our user study corroborates BAuth's attractiveness to car owners.
ContAuth
Authors: Chauhan Jagmohan , Kwon Young D. , Hui Pan , Mascolo Cecilia
Published: December 2020

User authentication is key in user authorization on smart and personal devices. Over the years, several authentication mechanisms have been proposed: these also include behavioral-based biometrics. However, behavioral-based biometrics suffer from two issues: they are prone to degradation in performance (accuracy) over time (e.g., due to data distribution changes arising from user behavior) and the need to learn the machine learning model from scratch, when adding new users. In this paper, we propose ContAuth, a system that can enhance the robustness of behavioral-based authentication. ContAuth continuously adapts to new incoming data (data incremental learning) and is able to add new users without retraining (class incremental learning). Specifically, ContAuth combines deep learning models with online learning models to achieve learning on the fly, thereby preventing a severe drop in the accuracy between sessions (over time). To add new users, ContAuth employs class incremental learning methods. We evaluate ContAuth on multiple behavior-based user authentication modalities: breathing, gait. and EMG. Our results show that our framework can help True Positive Rate (TPR) to remain high (>85 %) compared to other methods for all the modalities except EMG (>70%) across the sessions while keeping False Positive Rates (FPR) at a minimum (0-10%). It can achieve up to 35% improvement in TPR over a traditional deep learning model. Additionally, iCaRL (an incremental learning method) enables ContAuth to allow the addition of new users by alleviating catastrophic forgetting, to a large extent. Finally, we also show that ContAuth can be deployed efficiently and effectively on device, further providing data privacy.
VerHealth
Authors: Shezan Faysal Hossain , Hu Hang , Wang Gang , Tian Yuan
Published: December 2020

Healthcare applications on Voice Personal Assistant System (e.g., Amazon Alexa), have shown a great promise to deliver personalized health services via a conversational interface. However, concerns are also raised about privacy, safety, and service quality. In this paper, we propose VerHealth, to systematically assess health-related applications on Alexa for how well they comply with existing privacy and safety policies. VerHealth contains a static module and a dynamic module based on machine learning that can trigger and detect violation behaviors hidden deep in the interaction threads. We use VerHealth to analyze 813 health-related applications on Alexa by sending over 855,000 probing questions and analyzing 863,000 responses. We also consult with three medical school students (domain experts) to confirm and assess the potential violations. We show that violations are quite common, e.g., 86.36% of them miss disclaimers when providing medical information; 30.23% of them store user physical or mental health data without approval. Domain experts believe that the applications' medical suggestions are often factually-correct but are of poor relevance, and applications should have asked more questions before providing suggestions for over half of the cases. Finally, we use our results to discuss possible directions for improvements.
The Electropolishing of C-Steel in Orthophosphoric Acid Containing Methanolic Plant Extract
Authors: Taha Asia A. , Abouzeid Fatma M. , Elsadek Mohamed M. , Othman Yasmeen M.
Published: December 2020

Plant extracts have been regarded as “green” alternatives as additives for metal electropolishing improvement. Therefore, understanding the electrochemical properties and the reaction mechanisms of the electroactive compounds from the plant extracts is necessary to further explore the mechanism and application of the plant extract-based additives for metal dissolution. The C-steel electropolishing behavior in orthophosphoric acid using the galvanostatic polarization and weight loss methods was ascertained. This was inspected via anode potential-limiting current relationship measurement and comparison in a solution of regularly mounting concentrations (from 50 to 1800 ppm of methanolic marjoram, coriander seeds, chamomile, and guava leaves extract), and the influence of temperature on the dissolution kinetics was investigated. Surface morphologies, roughness, and reflection of investigated specimens were inspected with a scanning electron microscope (SEM), profilometry, and Vis-IR spectroscopy. Addition of methanolic plant extract to the electropolishing solution results in a lower limiting current. Retardation percentage gained from mass loss measurement is comparable with those obtained from measurements of galvanostatic polarization. Addition of 500 ppm of marjoram, coriander, chamomile, and guava leaves increases the degree of surface brightness and reflectance to 64.9, 56.59, 27, and 24.5, respectively, relative to electropolishing electrolyte-free solution 16. The roughness (Ra) decreased from 2.7 μm to 0.52 μm without addition of any material. Ra values are 0.28, 0.23, 0.21, and 0.17 μm in the presence of guava leaves, chamomile, coriander seeds, and marjoram.
Experimental Investigation on Stirring Rate Affecting Bubble Structure of Resin Anchor Agent and Anchoring Strength
Authors: Kan Jiaguang , Sun Yuantian , Wang Yifan , Yang Sen , Wang Peng
Published: December 2020

The function of a resin anchoring agent is to bond the rock of a borehole wall with the body of the anchor so the anchor can play an effective supporting role. The anchoring effect is related to the performance of the resin anchoring agent used and to the stirring rate applied during the anchor installation process. In this report, the stirring rate of the resin anchoring agent is evaluated and discussed in terms of how it affects pore structure and anchoring strength. When the stirring rate is in the range of 400–950 r/min, the uniaxial compressive strength of the resin anchoring agent increases proportionally with the stirring rate, and the compressive strength corresponding to the maximum stirring rate is 15.1% greater than that corresponding to the minimum stirring rate. Conversely, the pore size of the foam inside the resin anchoring agent is inversely proportional to the stirring rate, and the pore size corresponding to the maximum stirring rate is 15.1% smaller than that corresponding to the minimum stirring rate. The anchoring strength increases proportionally with the stirring rate when the stirring rate is between 400 and 800 r/min. Specifically, the anchoring strength associated with the maximum stirring rate is 9.2% greater than the anchoring strength corresponding to the minimum stirring rate. As the stirring time increases from 20 to 60 s, the anchoring force first increases and then decreases, with the optimal stirring time determined to be about 50 s. The results presented herein can be applied to improve anchor installation technology and the anchoring strength of resin anchoring agents.
Variceal Bleed and Portal Hypertensive Gastropathy in a Noncirrhotic Patient with Isolated Splenomegaly
Authors: Hasan S. M. Mahmudul , Dmitriew Meghan , Leonard Jennifer
Published: December 2020

Portal hypertension caused by cirrhosis is the most common etiology of esophageal varices. However, abnormalities of the splenoportal axis in the absence of liver disease may also cause portal hypertension resulting in varices. We report a rare case of esophageal variceal bleed in a noncirrhotic patient with isolated splenomegaly secondary to chronic granulocyte colony stimulating factor (G-CSF) therapy. The patient is a 26-year-old male with Cohen syndrome who required long-term G-CSF treatment for chronic neutropenia. He presented with large volume hematemesis and pancytopenia in the setting of known splenomegaly with no evidence of cirrhosis. An urgent EGD revealed active variceal bleeding and portal hypertensive gastropathy. The patient was appropriately resuscitated and underwent a successful transjugular intrahepatic portosystemic shunt and CT-guided coil placement for the bleeding varices. We are the first to report variceal bleed as a complication of long-term G-CSF use, a life-threatening consequence that requires urgent intervention.
Abstract A08: PI3Kbeta regulates beta-1 integrin signaling in invadopodia through formation of PI(3,4)P2
Authors: Erami Zahra , Bresnick Anne R. , Backer Jonathan M.
Published: December 2020

The PI3Kbeta isoform of PI 3-kinase, which is activated downstream from both RTKs and GPCRs, is an important regulator of invadopodia formation. We have previously reported that in MDA-MB-231 breast cancer cells, replacement of endogenous PI3Kbeta with kinase dead (KD) or GPCR-uncoupled (KK-DD) mutants leads to defects in invadopodia-mediated gelatin degradation. We have now studied the mechanism by which loss of PI3Kbeta signaling affects invadopodia. While the number of invadopodia precursors is unaffected by mutation of PI3Kbeta, formation of mature invadopodia is reduced in cells expressing KK-DD and KD PI3Kbeta mutants. Previous studies have demonstrated a role for beta-1 integrins in invadopodia maturation, and PI3Kbeta has been implicated in integrin signaling in platelets. We therefore tested whether mutation of PI3Kbeta would affect integrin signaling in breast cancer cells. In both haptotaxis and cell spreading assays on collagen I, cells expressing KD or KK-DD PI3Kbeta showed a significant impairment. Haptotaxis and cell spreading was also inhibited by TGX221 (PI3Kbeta inhibitor) and pertussis toxin (PTX), but not by specific inhibitors of other Class I PI3Ks. To distinguish whether PI3Kbeta was acting on integrins by inside-out versus outside-in mechanisms, we treated cells with the activating beta-1 integrin antibody TS2/16, which bypasses inside-out regulation of integrin binding. TS2/16 increased cell spreading on gelatin, but this was blocked by TGX221, suggesting that PI3Kbeta acts downstream of beta-1 integrins. Importantly, haptotaxis and cell spreading were not affected by an Akt inhibitor, but were blocked by an inhibitor of SHIP2, which hydrolyzes PIP3 to produce PI[3,4]P2. These data suggest that integrin signaling requires the coupling of Gbeta/gamma-mediated activation of PI3Kbeta to the production of PI[3,4]P2. Finally, to determine whether PI3Kbeta was involved in beta-1 integrin signaling in invadopodia, we plated starved cells on high-density fibrillar collagen (HDFC), which drives invadopodia formation through beta-1 integrin activation. Collagen degradation on HDFC was blocked by inhibition of PI3Kbeta or SHIP2, but not PI3Kalpha. Moreover, recruitment of the PI(3,4)P2 binding protein lamellipodin to invadopodia was reduced by inhibition of PI3Kbeta. In summary, beta-1 integrin signaling in the context of invadopodia maturation requires signaling through PI3Kbeta. We propose that heterotrimeric G-protein activation of PI3Kbeta is necessary for formation of PI(3,4)P2 in invadopodia, which is required for invadopodial maturation.

Citation Format: Zahra Erami, Anne R. Bresnick, Jonathan M. Backer. PI3Kbeta regulates beta-1 integrin signaling in invadopodia through formation of PI(3,4)P2 [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A08.
Abstract A18: Selectively targeting PI3K isoforms to treat glioblastoma
Authors: Pridham Kevin J. , Le Lamvy , Guo Sujuan , Varghese Robin T. , Liang Yanping , Rodgers Cara M. , Simonds Gary R. , Kelly Deborah F. , Sheng Zhi
Published: December 2020

The phosphatidylinositide 3-kinase (PI3K) family consists of four catalytic isoforms (PIK3CA, B, D, and G that encode p110alpha, beta, delta, and gamma, respectively), which play deviating roles in the formation and progression of different types of cancer such as breast and colon cancers. However, whether these PI3K isoforms function differently or equivalently in glioblastoma has not yet been explored. Glioblastoma is the most common and aggressive malignant glioma and patients often succumb to tumor recurrence, a progressive disease state that significantly contributes to the poor prognosis of glioblastoma. PI3K signaling is hyperactivated and mutated in glioblastoma; however, targeting PI3K to treat this cancer has not yet been successful. Given that PI3K isoforms are functionally divergent, it is very likely that selectively targeting PI3K catalytic isoforms is a more effective and discriminating approach to treating GBM. This possibility is supported by the following lines of evidence. Firstly, among four PI3K catalytic isoforms, PIK3CB is highly expressed in glioblastoma and high levels of PIK3CB exhibit the strongest correlation with the incidence, risk (time to develop recurrence), and survival of glioblastoma recurrence based upon expression data of PI3K isoforms and patient data from The Cancer Genome Atlas. Secondly, PI3K is often hyperactivated in glioblastoma cells with high levels of p110beta, but not other p110s, and depletion of p110beta inactivates, whereas knockdown of other p110s has no effect on, PI3K activity as well as glioblastoma cell survival. Thirdly, the selective activation of p110beta may be due primarily to a gap junction protein connexin 43 because this cell surface protein activates p110beta in p110beta-high glioblastoma cells through a selective interaction between connexin 43 and p110beta. Lastly, glioblastoma cells display differential responses to p110 isoform-selective inhibitors. Only p110beta selective inhibitors effectively activate apoptosis in, suppress the viability of, and impede the xenograft growth of p110beta hyperactivated glioblastoma cells. More importantly, p110beta inhibitors are much less toxic to normal astrocytes than other p110 inhibitors. These findings have revealed molecular details underlying the divergent roles of PI3K catalytic isoforms in glioblastoma, which will foster a rational design of more effective PI3K-based therapies for this deadly disease.

Citation Format: Kevin J. Pridham, Lamvy Le, Sujuan Guo, Robin T. Varghese, Yanping Liang, Cara M. Rodgers, Gary R. Simonds, Deborah F. Kelly, Zhi Sheng. Selectively targeting PI3K isoforms to treat glioblastoma [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A18.
Abstract A26: mTOR inhibition promotes differentiation of human regulatory T cells via privileged mRNA translation
Authors: Volta Viviana , Ernlund Amanda , Gadi Abhilash , Valeta-Magara Amanda , de la Parra Columba , Patel Preeyam , Schneider Robert J.
Published: December 2020

Regulatory T cells (Tregs) maintain immune system homeostasis in the organism. In the tumor microenvironment, however, Tregs can hinder the antitumor immune response. Treg maturation in peripheral sites (pTregs) requires inhibition of protein kinase mTORC1, which paradoxically blocks mRNA translation. mTORC1 phosphorylates (inactivates) 4E-BP1, a negative regulator of the translation initiation factor eIF4E. When mTORC1 is active, 4E-BP1 is hyperphosphorylated and releases eIF4E, which can then bind the mRNA cap structure and promote eIF4F complex assembly and ribosome recruitment. Inhibition of mTORC1 results in hypo-phosphorylation (activation) of 4E-BP1, which then binds and sequesters eIF4E, preventing its interaction with the cap and ribosome association to the mRNA. Using human CD4+ T cells differentiated in vitro, we show that mTORC1 inhibition strongly impairs protein synthesis, yet with exposure to TGFbeta is essential to mediate iTreg differentiation and immune suppression activity. We found that TGFbeta reprograms the T-cell transcriptome, while mTORC1 inhibition reprograms the translatome (genome-wide translation signature), mediating Treg differentiation. Genome-wide transcription and translation profiling identified TGFbeta-upregulated mRNAs resistant to mTORC1 inhibition, in part due to their 5'-untranslated regions, that induce Treg differentiation and immune-suppression activity. These include canonical pTreg fate-determining mRNAs FOXP3, CTLA-4, CD101 and CD103, among others. Inhibition of mTORC1 alone, or TGFbeta alone, induces iTregs with poor immune-suppression activity. Treg differentiation is therefore mediated by an mTORC1-independent privileged mRNA translation mechanism that converts activated CD4+ T cells to Tregs. These findings are quite relevant in the tumor microenvironment, where mTORC1-inhibiting conditions such as hypoxia and deprivation of nutrients and energy are present. Investigation of molecular targets acting in this mTORC1/eIF4E-independent translation of Treg mRNAs is ongoing. These targets could be drugged to selectively inhibit Treg differentiation in the tumor microenvironment, thus allowing effector cells to mount the response against cancer cells.

Citation Format: Viviana Volta, Amanda Ernlund, Abhilash Gadi, Amanda Valeta-Magara, Columba de la Parra, Preeyam Patel, Robert J. Schneider. mTOR inhibition promotes differentiation of human regulatory T cells via privileged mRNA translation [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A26.
Abstract A29: Targeted disruption of PI3K/Akt/mTOR signaling pathway induces cell cycle arrest, apoptosis, autophagy, and inhibits inflammation, invasion, and angiogenesis of OSCC cells
Authors: Aggarwal Sadhna , John Sarah , Das Satya N. , Sharma Suresh C.
Published: December 2020

Purpose: The phosphoinositide-3-kinase (PI3K) pathway is frequently altered in human cancer. This has led to the development and study of novel PI3K inhibitors for targeted therapy and also to overcome resistance to radiotherapy.

Method: The antitumor effects of PI3K inhibitors (PI-828, PI-103 and PX-866) in terms of cell proliferation, colony formation, induction of apoptosis, cell cycle arrest, invasion, autophagy, and pNF- κB/p65 translocation in SCC-4, SCC-9 and SCC-25 cells were studied by performing MTT, clonogenic, DAPI staining, propidium iodide staining, annexin–V binding, Matrigel invasion, acridine orange staining and immunofluorescence assay. Western blot assay was performed to assess the alteration in the expression of various proteins.

Result: PI-828 and PI-103 treatment exhibited dose-dependent inhibition of growth and proliferation of OSCC cells with a concomitant induction of apoptosis, altered cell cycle regulation and decreased invasiveness (p <0.01). PX-866 induced apoptosis, cell cycle arrest, autophagy and a significant decrease in the invasiveness of oral cancer cells as compared to untreated cells (p <0.01). These compounds significantly reduced expression of COX-2, Cyclin-D and VEGF in the treated cells besides cytoplasmic accumulation of pNF-κB/p65 protein. In addition to PI3Kα, inactivation of downstream components, i.e., Akt and mTOR was seen.

Conclusion: PI3K inhibitors such as PI-103, PI-828 and PX-866 may be developed as potential chemotherapeutic agents for effective treatment of OSCC and other malignancies associated with activated PI3K/Akt pathway.

Note: This abstract was not presented at the conference.

Citation Format: Sadhna Aggarwal, Sarah John, Satya N. Das, Suresh C. Sharma. Targeted disruption of PI3K/Akt/mTOR signaling pathway induces cell cycle arrest, apoptosis, autophagy, and inhibits inflammation, invasion, and angiogenesis of OSCC cells [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A29.
Abstract B07: TAK228 enhances antitumor activity of eribulin in triple-negative breast cancer
Authors: Owusu-Brackett Nicci , Evans Kurt W. , Akcakanat Argun , Yuca Erkan , Dumbrava Ecaterina Ileana , Janku Filip , Meric-Bernstam Funda
Published: December 2020

Background: Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) negatively regulates the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway. Triple-negative breast cancers (TNBC) are often PTEN-deficient, making mTOR a compelling target. We evaluated the efficacy of catalytic mTOR inhibitor TAK228 alone and in combination with eribulin in TNBC.

Methods: We tested TAK228 in combination with eribulin in a panel of TNBC cell lines with cell proliferation assays. Western blot analysis was performed to assess PTEN status and PI3K pathway inhibition. In vivo, antitumor efficacy of TAK228 as a single agent as well as in combination with eribulin was evaluated.

Results: Five of eight triple-negative breast cell lines were sensitive to TAK228, independent of PIK3CA/PTEN status. Western blotting demonstrated inhibition of mTORC1/2 signaling as demonstrated by decreased phospho-AKT, phospho-S6 and phospho-4EBP1. In vitro, TAK228 was synergistic with eribulin in all eight TNBC cell lines. The combination of TAK228 and eribulin did not enhance apoptosis but increased G2/M growth arrest (p<0.001). In vivo, TAK228 led to modest growth inhibition in TNBC derived xenografts with no tumor regression observed. In two TNBC PDXs with PTEN loss, one with intrinsic eribulin sensitivity, another eribulin resistance, TAK228 in combination with eribulin did not enhance in vivo efficacy. In a third PTEN-negative TNBC model, eribulin alone achieved disease stabilization, but the combination of TAK228 and eribulin led to significantly smaller tumor volumes compared to eribulin alone (p<0.0001).

Conclusion: TAK228 enhanced the antitumor efficacy of eribulin in TNBC models in vitro and enhanced in vivo activity in selected models. Further study is needed to determine the potential of this combination and optimal patient selection strategies.

Citation Format: Nicci Owusu-Brackett, Kurt W. Evans, Argun Akcakanat, Erkan Yuca, Ecaterina Ileana Dumbrava, Filip Janku, Funda Meric-Bernstam. TAK228 enhances antitumor activity of eribulin in triple-negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr B07.