bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Exothermic Flux for Enhanced Penetration in Submerged Arc Welding
Authors: Kumar Aditya , Singh Kulwant
Published: September 2019

An exothermic flux for submerged arc welding process has been developed which is capable of enhancing weld penetration of the joint. For this purpose, thermit mixture in different proportions (20% and 40%) has been added to the parent flux by agglomeration process. Beads on plate were deposited using parent and developed exothermic fluxes for a comparative study. EH14 filler wires in combination with parent and exothermic fluxes were used in this investigation. The effects of welding parameters and exothermic flux on weld penetration were investigated and the results have been presented in this paper. It has been found that the penetration increases from 2.95 to 3.51[Formula: see text]mm with 40% thermit mixture addition to the parent flux. It is further observed that penetration increases with increase in the amount of thermit mixture added. A mathematical model has been developed to predict weld penetration or select suitable welding parameters to obtain the desired penetration. The significance of coefficients was tested using Student’s [Formula: see text]-test and the adequacy of developed model was tested using [Formula: see text]-test. The effects of various parameters on penetration have been presented in graphical form for better understanding.
Experimental Evaluation for Improving Multiple Quality Characteristics of Drilled Holes: A Case Study on Drilling of Ti6Al4V
Authors: Chatterjee Suman , Mahapatra Siba Sankar , Abhishek Kumar
Published: September 2019

Titanium alloys find increased applications in many engineering fields such as bio-medical, aerospace, electronics and automobile industries due to their superior physical properties such as high specific strength, weight to strength ratio, corrosive resistant and toughness. Low thermal conductivity of titanium alloys makes it difficult to machine since high cutting temperature is generated at tool work piece interface. As it is highly chemically reactive at high temperature, work piece is adhered to the tool surface. The present work aims at investigating the effect of drilling process parameters viz. spindle speed, drill bit diameter and feed rate on machining performance measures such as burr height at entry and exit, surface roughness and circularity at entry and exit. In order to optimize all the performance measures simultaneously, the present investigation utilizes a hybrid approach known as superiority and inferiority ranking method combined with technique for order preference by similarity to ideal solution (SIR-TOPSIS) to convert these characteristics into single equivalent characteristic ([Formula: see text]-flow). A statistically valid empirical relationship is developed for r-flow in terms of machining parameters using nonlinear regression technique. The study aims at attaining optimal parametric setting that maximizes [Formula: see text]-flow. To optimize [Formula: see text]-flow, an improved version of meta-heuristic evolutionary algorithm known as harmony search (HS) algorithm is implemented. The confirmatory experiment suggests the robustness of the methodology in optimizing the drilling operation.
DETERMINING THE OPTIMAL TIME TO LAUNCH AN EMERGING INNOVATION IN A MARKET
Authors: HÄCKEL BJÖRN , STIRNWEISS DOMINIC
Published: September 2019

Investments in emerging technologies and the development of related emerging innovations are necessary to compete in the long term. The market entry timing plays an important role in generating decisive competitive advantages over competitors through investments in emerging innovations. Different market entry strategies offer varied opportunities and risks, which firms must take into account when choosing the optimal time to enter the market. This study develops an optimisation model to make an economically appropriate ex-ante decision in this choice by accounting for several relevant factors and weighing up possible opportunities and risks of the chosen market entry strategy. The evaluation of the simulation results shows that the considered factors influence the optimal market entry to varying extents and that both early and late market entry can be advantageous for companies.
Mobile Gait Analysis Using Foot-Mounted UWB Sensors
Authors: Anderson Boyd , Shi Mingqian , Tan Vincent Y. F. , Wang Ye
Published: September 2019

We demonstrate a new foot-mounted sensor system for mobile gait analysis which is based on Ultra Wideband (UWB) technology. Our system is wireless, inexpensive, portable, and able to estimate clinical measurements that are not currently available in traditional Inertial Measurement Unit (IMU) based wearables such as step width and foot positioning. We collect a dataset of over 2000 steps across 21 people to test our system in comparison with the clinical gold-standard GAITRite, and other IMU-based algorithms. We propose methods to calculate gait metrics from the UWB data that our system collects. Our system is then validated against the GAITRite mat, measuring step width, step length, and step time with mean absolute errors of 0.033m, 0.032m, and 0.012s respectively. This system has the potential for use in many fields including sports medicine, neurological diagnostics, fall risk assessment, and monitoring of the elderly.
LungTrack
Authors: Chen Lili , Xiong Jie , Chen Xiaojiang , Lee Sunghoon Ivan , Zhang Daqing , Yan Tao , Fang Dingyi
Published: September 2019

Respiration rate sensing plays a critical role in elderly care and patient monitoring. The latest research has explored the possibility of employing Wi-Fi signals for respiration sensing without attaching a device to the target. A critical issue with these solutions includes that good monitoring performance could only be achieved at certain locations within the sensing range, while the performance could be quite poor at other "dead zones." In addition, due to the contactless nature, it is challenging to monitor multiple targets simultaneously as the reflected signals are often mixed together. In this work, we present our system, named LungTrack, hosted on commodity RFID devices for respiration monitoring. Our system retrieves subtle signal fluctuations at the receiver caused by chest displacement during respiration without need for attaching any devices to the target. It addresses the dead-zone issue and enables simultaneous monitoring of two human targets by employing one RFID reader and carefully positioned multiple RFID tags, using an optimization technique. Comprehensive experiments demonstrate that LungTrack can achieve a respiration monitoring accuracy of greater than 98% for a single target at all sensing locations (within 1st -- 5th Fresnel zones) using just one RFID reader and five tags, when the target's orientation is known a priori. For the challenging scenario involve two human targets, LungTrack is able to achieve greater than 93% accuracy when the targets are separated by at least 10 cm.
Vision2Sensor
Authors: Radu Valentin , Henne Maximilian
Published: September 2019

Mobile and wearable sensing devices are pervasive, coming packed with a growing number of sensors. These are supposed to provide direct observations about user activity and context to intelligent systems, and are envisioned to be at the core of smart buildings, towards habitat automation to suit user needs. However, much of this enormous sensing capability is currently wasted, instead of being tapped into, because developing context recognition systems requires substantial amount of labeled sensor data to train models on. Sensor data is hard to interpret and annotate after collection, making it difficult and costly to generate large training sets, which is now stalling the adoption of mobile sensing at scale. We address this fundamental problem in the ubicomp community (not having enough training data) by proposing a knowledge transfer framework, Vision2Sensor, which opportunistically transfers information from an easy to interpret and more advanced sensing modality, vision, to other sensors on mobile devices. Activities recognised by computer vision in the camera field of view are synchronized with inertial sensor data to produce labels, which are then used to dynamically update a mobile sensor based recognition model. We show that transfer learning is also beneficial to identifying the best Convolutional Neural Network for vision based human activity recognition for our task. The performance of a proposed network is first evaluated on a larger dataset, followed by transferring the pre-trained model to be fine-tuned on our five class activity recognition task. Our sensor based Deep Neural Network is robust to withstand substantial degradation of label quality, dropping just 3% in accuracy on induced degradation of 15% to vision generated labels. This indicates that knowledge transfer between sensing modalities is achievable even with significant noise introduced by the labeling modality. Our system operates in real-time on embedded computing devices, ensuring user data privacy by performing all the computations in the local network.
micro-Stress EMA
Authors: King Zachary D. , Moskowitz Judith , Egilmez Begum , Zhang Shibo , Zhang Lida , Bass Michael , Rogers John , Ghaffari Roozbeh , Wakschlag Laurie , Alshurafa Nabil
Published: September 2019

High levels of stress during pregnancy increase the chances of having a premature or low-birthweight baby. Perceived self-reported stress does not often capture or align with the physiological and behavioral response. But what if there was a self-report measure that could better capture the physiological response? Current perceived stress self-report assessments require users to answer multi-item scales at different time points of the day. Reducing it to one question, using microinteraction-based ecological momentary assessment (micro-EMA, collecting a single in situ self-report to assess behaviors) allows us to identify smaller or more subtle changes in physiology. It also allows for more frequent responses to capture perceived stress while at the same time reducing burden on the participant. We propose a framework for selecting the optimal micro-EMA that combines unbiased feature selection and unsupervised Agglomerative clustering. We test our framework in 18 women performing 16 activities in-lab wearing a Biostamp, a NeuLog, and a Polar chest strap. We validated our results in 17 pregnant women in real-world settings. Our framework shows that the question "How worried were you?" results in the highest accuracy when using a physiological model. Our results provide further in-depth exposure to the challenges of evaluating stress models in real-world situations.
FMT
Authors: Li Franklin Mingzhe , Chen Di Laura , Fan Mingming , Truong Khai N.
Published: September 2019

Older adults sometimes forget about whether or not they have completed routine actions and the states of objects that they have interacted with (e.g., the kitchen stove is on or off). In this work, we explore whether video clips captured from a body-worn camera every time objects of interest are found within its field of view can help older adults determine if they have completed certain actions with these objects and what their states are. We designed FMT ("Fiducial Marker Tracker")---a real-time capture and access application that opportunistically captures video clips of objects the user interacts with. To do this, the user places fiducial markers close to objects which would be captured when the marker enters the user's body-worn camera's field of view. We examine and discuss what objects this system would be best suited to track, and the usefulness and usability of this approach. FMT successfully captured direct interactions with an object at an average rate of 75.6% across all participants (SD = 9.9%). Our results also reveal how, what, and why users would use such a system for help.
I3
Authors: Lu Li , Yu Jiadi , Chen Yingying , Zhu Yanmin , Li Minglu , Xu Xiangyu
Published: September 2019

The scrolling interaction is a pervasive human-computer interaction on smartphones, which can reflect intrinsic characteristics during dynamic browsings. Different from extrinsic statistical measures like frequency of visits and dwell time, intrinsic features underlying scrolling interactions reveal fine-grained implicit feedbacks about user interests. Toward this end, we explore user interest inference by extracting efficient browsing features from scrolling human-computer interactions on smartphones. In this paper, we first analyze browsing traces of 40 volunteers, and find two intrinsic browsing features underlying scrolling interactions, i.e., browsing velocity stability and browsing velocity sequence, which are tightly related to user interests. Inspired by the observation, we propose an Intelligent Interest Inference system, I3, which infers user interests through sensing scrolling interactions during browsings. Specifically, I3 first extracts the two intrinsic browsing features from users' scrolling interactions. Then, I3 applies a Naive Bayesian-based approach to construct an interest discriminator for coarse-grained user interest (i.e., like-preferred or dislike-preferred) inference. Furthermore, we develop a deep learning-based approach for I3 to train rating classifiers for fine-grained rating inference in like-preferred and dislike-preferred browsings respectively. Finally, I3 utilizes the interest discriminator and rating classifiers to infer exact user ratings about browsing contents on smartphones. Experimental results under browsing traces of 46 volunteers present that I3 achieves 92.4% overall accuracy in interest inference.
DeepNavi
Authors: Niu Qun , Liu Ning , Huang Jianjun , Luo Yangze , He Suining , He Tao , Chan S.-H. Gary , Luo Xiaonan
Published: September 2019

Indoor navigation plays a crucial role in indoor location-based services. Single signal-based navigation systems, however, are prone to sensor noises, signal ambiguities and are specific to trial sites. To address these, existing work fuses different signals with user trajectories. Despite their accuracy, many of them are specific to input signals and navigation modes (e.g., spot-based or sequence-based) and are computationally expensive in large sites. Additionally, they do not give predictive uncertainty estimations, leading to a lack of trust in navigation instructions.

In this paper, we propose a unified framework for accurate indoor navigation in various modes with different inputs, termed DeepNavi. We exploit either convolutional or recurrent neural networks for initial feature extraction. Afterwards, we insert fully connected layers to generalize extracted signal-dependent features to a shared domain before fusion. Then, we leverage state-of-the-art ensemble learning to learn multiple predictive models. By combining them together, we further reduce the impact of signal noises and achieve high accuracy. Finally, we insert mixture density networks to model more generalized data distributions and provide uncertainty estimations. We have implemented DeepNavi and conducted extensive experiments in two different trial sites with different signal combinations. Experimental results show that DeepNavi reduces location errors by more than 20% with comparable orientation accuracy.
Leveraging Routine Behavior and Contextually-Filtered Features for Depression Detection among College Students
Authors: Xu Xuhai , Chikersal Prerna , Doryab Afsaneh , Villalba Daniella K. , Dutcher Janine M. , Tumminia Michael J. , Althoff Tim , Cohen Sheldon , Creswell Kasey G. , Creswell J. David , Mankoff Jennifer , Dey Anind K.
Published: September 2019

The rate of depression in college students is rising, which is known to increase suicide risk, lower academic performance and double the likelihood of dropping out of school. Existing work on finding relationships between passively sensed behavior and depression, as well as detecting depression, mainly derives relevant unimodal features from a single sensor. However, co-occurrence of values in multiple sensors may provide better features, because such features can describe behavior in context. We present a new method to extract contextually filtered features from passively collected, time-series mobile data via association rule mining. After calculating traditional unimodal features from the data, we extract rules that relate unimodal features to each other using association rule mining. We extract rules from each class separately (e.g., depression vs. non-depression). We introduce a new metric to select a subset of rules that distinguish between the two classes. From these rules, which capture the relationship between multiple unimodal features, we automatically extract contextually filtered features. These features are then fed into a traditional machine learning pipeline to detect the class of interest (in our case, depression), defined by whether a student has a high BDI-II score at the end of the semester. The behavior rules generated by our methods are highly interpretable representations of differences between classes. Our best model uses contextually-filtered features to significantly outperform a standard model that uses only unimodal features, by an average of 9.7% across a variety of metrics. We further verified the generalizability of our approach on a second dataset, and achieved very similar results.
Perceived Organizational Support: Why Caring About Employees Counts
Authors: Eisenberger Robert , Rhoades Shanock Linda , Wen Xueqi
Published: September 2019

According to organizational support theory (OST), employees develop a general perception concerning the extent to which their work organization values their contribution and cares about their well-being (perceived organizational support, or POS). We explain OST and review empirical POS findings relevant to OST's main propositions, including new findings that suggest changes to OST. Major antecedents of POS include fairness, support from leaders, and human resource practices and work conditions, especially to the extent that employees perceive these as the discretionary choices of organizations. Among more recent findings, the average level of POS has modestly increased over the past three decades in the United States. Furthermore, POS appears to have stronger positive outcomes in Eastern cultures than Western cultures. Some additional promising recent areas of research on POS include trickle-down effects, POS of groups, and POS as relevant to creativity and innovation, positive emotional outcomes, and well-being.
Size of the Largest Component in a Critical Graph
Authors: Wang Bin , Zou Lang
Published: September 2019

In this paper, by the branching process and the martingale method, we prove that the size of the largest component in the critical random intersection graph G(n, [n5/3], p) is asymptotically of order n2/3 and the width of scaling window is n−1/3.
A Compact Wideband Printed Antenna for 4G/5G/WLAN Wireless Applications
Authors: Yang Ming , Sun Yufa , Li Fan
Published: September 2019

A compact wideband printed antenna with deca-band 4G/5G/WLAN for mobile phone devices is proposed in this paper. The complete structure is composed of a monopole antenna and a coupling strip, occupying a small C-shape PCB area of 27 × 10.8 mm2. This antenna, which is printed on FR4 substrate with 0.8 mm thickness and fed by a coaxial cable, can provide three wide operating bandwidths that cover 685–1012 MHz, 1596–2837 MHz, and 3288–3613 MHz for 4G/5G/WLAN communication systems. The gains and total radiation efficiencies of the antenna in the low, middle, and high bands are 1.4 dBi–2.5 dBi and 38%–47%, respectively. Besides, the measured results are in good agreement with the simulated results. Further experiments demonstrate that the proposed antenna exhibits a good performance for mobile phones.
Preparation of a Composite Material AC/Cu-BTC with Improved Water Stability and n-Hexane Vapor Adsorption
Authors: Li Manlin , Huang Weiqiu , Tang Bo , Song Fujiao , Lv Aihua , Ling Xiang
Published: September 2019

The Cu-BTC, a widely studied metal-organic framework (MOF), has been applied in various fields such as gas adsorption, separation, storage, and catalysis. However, the Cu-BTC collapses due to the replacement of the organic linker by water molecules under humid conditions, which limits its practical application in industries. In consideration of the undesirable water effect on the framework stability of Cu-BTC, a stable activated carbon (AC) was incorporated into it by the in situ method to yield a composite material AC/Cu-BTC with high water stability. XRD and SEM patterns proved that the AC7%/Cu-BTC successfully retains its crystal structure after being exposed to water molecules. The adsorption amount of n-hexane vapor of the AC7%/Cu-BTC after water vapor adsorption-thermal desorption is 307% of that of the Cu-BTC. The addition of the AC changes the adsorption active sites and reduces the strong affinity of the Cu-BTC to water molecules, resulting in the AC7%/Cu-BTC having a much lower adsorption rate for water vapor than the Cu-BTC. Therefore, the AC7%/Cu-BTC can be protected from a large amount of water molecules and avoid structural collapse caused by the disconnection between the copper center and the organic linker. The composite displays a potential value for stable applications of MOF-based materials under ambient conditions.
Comparative Studies of Combined Influence of Variables on the Esterification Degree of Pectin Extracted by Sulfuric Acid and Citric Acid
Authors: Li Jun , Zhang Ling , Li Jun-fang , Li De-qiang
Published: September 2019

The influence of extraction variables on degree of esterification (DE) of pectin was studied due to the significant effects of DE on the properties of the pectin-based functional biomaterials. The extracting agents (sulfuric acid and citric acid), pH value of extraction solution, extraction time, and temperature were selected to study the hydrolysis reaction of carboxylic acid ester by response surface methodology (RSM). The hydrolysis reaction occurred more violently in the weak organic acid solution than that in the strong inorganic acid solution. The DE was significantly influenced by pH of extraction solution, extraction time, and temperature through the analysis of variance. In addition, the values of DE reduced with the increasing of extraction temperature, lapse of time, and decreasing of pH value. What is more, the effects of extraction conditions on the yield, monosaccharide composition, content of protein, and ferulic acid were also studied. It is evident that the lower pH value contributed to higher extraction yield. The content of Total CH and GalA of pectin extracted by sulfuric acid were higher than that of pectin extracted by citric acid, and the content of monosaccharide showed an opposite trend.
Impact of Molybdenum Compounds as Anticancer Agents
Authors: Odularu Ayodele T. , Ajibade Peter A. , Mbese Johannes Z.
Published: September 2019

The aim of this mini review was to report the molybdenum compound intervention to control cancer disease. The intervention explains its roles and progress from inorganic molybdenum compounds via organomolybdenum complexes to its nanoparticles to control oesophageal cancer and breast cancer as case studies. Main contributions of molybdenum compounds as anticancer agents could be observed in their nanofibrous support with suitable physicochemical properties, combination therapy, and biosensors (biomarkers). Recent areas in anticancer drug design, which entail the uses of selected targets, were also surveyed and proposed.
Liquid Biopsy Detects Relapse Five Months Earlier than Regular Clinical Follow-Up and Guides Targeted Treatment in Breast Cancer
Authors: Cheng Fiona Tsui-Fen , Lapke Nina , Wu Chin-Chu , Lu Yen-Jung , Chen Shu-Jen , Yu Pei-Ning , Liu Yen-Ting , Tan Kien Thiam
Published: September 2019

Genetic alterations in circulating tumor DNA (ctDNA) are an emerging biomarker for the early detection of relapse and have the potential to guide targeted treatment. ctDNA analysis is often performed by droplet digital PCR; however, next-generation sequencing (NGS) allows multigene testing without having to access a tumor sample to identify target alterations. Here, we report the case of a stage III hormone receptor-positive breast cancer patient who remained symptomless after receiving surgery and adjuvant chemotherapy. Liquid biopsy analysis by NGS revealed the presence of a ctDNA PIK3CA N345K mutation five months before the detection of relapse with multiple liver metastases by regular clinical follow-up. To date, clinical implications of the PIK3CA N345K variant remain insufficiently investigated; however, everolimus treatment resulted in the shrinkage of tumor lesions and decreased the levels of tumor markers. Four months after treatment initiation, a second ctDNA analysis suggested a relapse, and the patient clinically progressed after five months of everolimus therapy. This case report demonstrates the value of ctDNA analysis by NGS for the early detection of relapse in breast cancer patients. The study further indicates its usefulness for the choice of targeted treatments, suggesting that the variant PIK3CA N345K might be associated with everolimus sensitivity.
Arithmetic-Analytic Representation of Peano Curve
Authors: Yang Guangjun , Yang Xiaoling , Wang Ping
Published: September 2019

In this work, we obtained a nonmatrix analytic expression for the generator of the Peano curve. Applying the iteration method of fractal, we established a simple arithmetic-analytic representation of the Peano curve as a function of ternary numbers. We proved that the curve passes each point in a unit square and that the coordinate functions satisfy a Hölder inequality with index α=1/2, which implies that the curve is everywhere continuous and nowhere differentiable.
A Complication of an Endoscopic Pigtail Stent Migration into the Cavity during Deployment as a Treatment for Gastric Leak
Authors: AlAtwan Abrar A. , AlJewaied Ali , AlKhadher Talal , AlHaddad Mohannad , Siddique Iqbal
Published: September 2019

Gastric leak following gastrointestinal surgery is the most dreadful complication, which implies long hospital stay, morbidities, and not irrelevant mortalities. There is no standard recommendation for treating postlaparoscopic sleeve gastrectomy leak, which makes its management challenging. Endoscopic internal drainage by double-pigtail drains currently became the recommended approach. Complications to this approach include bleeding, ulceration at the tip of the double-pigtail stent, and uncommon migration. Here, we report our experience with drain displacement into the cavity while deployment in a patient who experienced gastric leakage after undergoing sleeve gastrectomy.
Research on Dual-Carrier Pulse-Train-Controlled Buck Converter
Authors: Qin Ming , Li Shiwei
Published: September 2019

In order to solve the low-frequency oscillation of pulse-train- (PT-) controlled switching converter operating in a continuous conduction mode (CCM), a dual-carrier pulse-train (DCPT) control technique is proposed in this paper. With the CCM buck converter as an example, the operational principle, pulse control law, and output voltage ripple of the DCPT-controlled converter are studied. The experimental results are provided to verify the theoretical analysis and simulation results. Compared with the PT-controlled converter, the DCPT-controlled CCM buck converter enjoys much better operating characteristics and smaller output voltage ripple.
The Influence of Surface Coatings of Silver Nanoparticles on the Bioavailability and Toxicity to Elliptio complanata Mussels
Authors: Auclair J. , Turcotte P. , Gagnon C. , Peyrot C. , Wilkinson K. J. , Gagné F.
Published: September 2019

Nanomaterials could be modified with various coatings which could modulate their behavior in the environment, bioavailability and toxicity. The purpose of this study was to determine if the selected coatings of silver nanoparticles (nAg) could influence the fate, bioavailability, and toxicity toward suspension feeding freshwater mussels, Elliptio complanata. Mussels were exposed for 96 h to 50 μg/L of nAg with the following surface coatings: citrate, silicate (Si), polyvinylpyrrolidone (PVP), and branched polyethylenimine (bPEI). After the exposure period, mussels were analyzed for total Ag, resistance to air emersion, oxidative stress, genotoxicity, and autophagosome protein uptake (protein ubiquitinylation) in gills and digestive glands. The data revealed that citrate- and PVP-coated nAg were 2 times more abundant in the digestive gland compared to bPEI- and Si-coated nAg with estimated bioaccumulation factors between 5 and 10. The data revealed that tissue Ag levels were closely associated with air survival time, weight loss during air exposure, DNA strand breaks, LPO, and protein-ubiquitin levels in the digestive gland. The data supports the hypothesis that the coatings could influence bioavailability and toxicity in freshwater mussels.
Oncogenic KRAS Sensitizes Lung Adenocarcinoma to GSK-J4–Induced Metabolic and Oxidative Stress
Authors: Hong Beom-Jin , Park Woo-Yong , Kim Hwa-Ryeon , Moon Jin Woo , Lee Ho Yeon , Park Jun Hyung , Kim Seon-Kyu , Oh Youngbin , Roe Jae-Seok , Kim Mi-Young
Published: September 2019

Genetic and epigenetic changes (e.g., histone methylation) contribute to cancer development and progression, but our understanding of whether and how specific mutations affect a cancer's sensitivity to histone demethylase (KDM) inhibitors is limited. Here, we evaluated the effects of a panel of KDM inhibitors on lung adenocarcinomas (LuAC) with various mutations. Notably, LuAC lines harboring KRAS mutations showed hypersensitivity to the histone H3K27 demethylase inhibitor GSK-J4. Specifically, GSK-J4 treatment of KRAS mutant–containing LuAC downregulated cell-cycle progression genes with increased H3K27me3. In addition, GSK-J4 upregulated expression of genes involved in glutamine/glutamate transport and metabolism. In line with this, GSK-J4 reduced cellular levels of glutamate, a key source of the TCA cycle intermediate α-ketoglutarate (αKG) and of the antioxidant glutathione, leading to reduced cell viability. Supplementation with an αKG analogue or glutathione protected KRAS-mutant LuAC cells from GSK-J4–mediated reductions in viability, suggesting GSK-J4 exerts its anticancer effects by inducing metabolic and oxidative stress. Importantly, KRAS knockdown in mutant LuAC lines prevented GSK-J4–induced decrease in glutamate levels and reduced their susceptibility to GSK-J4, whereas overexpression of oncogenic KRAS in wild-type LuAC lines sensitized them to GSK-J4. Collectively, our study uncovers a novel association between a genetic mutation and KDM inhibitor sensitivity and identifies the underlying mechanisms. This suggests GSK-J4 as a potential treatment option for cancer patients with KRAS mutations.

Significance:

This study not only provides a novel association between KRAS mutation and GSK-J4 sensitivity but also demonstrates the underlying mechanisms, suggesting a potential use of GSK-J4 in cancer patients with KRAS mutations.
A Phase I and Pharmacokinetic Study of Oral Dabrafenib in Children and Adolescent Patients with Recurrent or Refractory BRAF V600 Mutation–Positive Solid Tumors
Authors: Kieran Mark W. , Geoerger Birgit , Dunkel Ira J. , Broniscer Alberto , Hargrave Darren , Hingorani Pooja , Aerts Isabelle , Bertozzi Anne-Isabelle , Cohen Kenneth J. , Hummel Trent R. , Shen Violet , Bouffet Eric , Pratilas Christine A. , Pearson Andrew D.J. , Tseng Lillian , Nebot Noelia , Green Steven , Russo Mark W. , Whitlock James A.
Published: September 2019

Purpose:

The 2-part, phase I/IIa, open-label study (NCT01677741) sought to determine the safety, tolerability, pharmacokinetics, and preliminary activity of dabrafenib in pediatric patients with advanced BRAF V600–mutated cancers.

Patients and Methods:

This phase I dose-finding part treated patients ages 1 to <18 years with BRAF V600 mutation–positive tumors with oral dabrafenib 3 to 5.25 mg/kg/day to determine the RP2D based on safety and drug exposure target.

Results:

Between May 2013 and November 2014, 27 patients [12 male; median age, 9 years (range, 1–17 years)] with BRAF V600–mutant solid tumors recurrent/refractory to treatment (low- or high-grade glioma, Langerhans cell histiocytosis, neuroblastoma, or thyroid cancer) were enrolled. The median treatment duration was 75.6 weeks (range, 5.6–148.7 weeks), with 63% treated for >52 weeks and 52% undergoing treatment at data cutoff date. The most common grade 3/4 adverse events suspected to be related to study drug were maculopapular rash and arthralgia (2 patients each). No dose-limiting toxicities were observed. Pharmacokinetic analyses showed a dose-dependent increase in AUC0–12 and achievement of adult exposure levels at the recommended phase II doses of 5.25 mg/kg/day (age <12 years) and 4.5 mg/kg/day (age ≥12 years) divided into 2 equal doses daily, not exceeding 300 mg daily.

Conclusions:

In this first clinical trial in pediatric patients with pretreated BRAF V600–mutant tumors, dabrafenib was well tolerated while achieving target exposure levels; the average treatment duration was >1 year with many patients still on treatment. The phase II component is also closed and will be reported separately.
NKG2D Controls Natural Reactivity of Vγ9Vδ2 T Lymphocytes against Mesenchymal Glioblastoma Cells
Authors: Chauvin Cynthia , Joalland Noémie , Perroteau Jeanne , Jarry Ulrich , Lafrance Laura , Willem Catherine , Retière Christelle , Oliver Lisa , Gratas Catherine , Gautreau-Rolland Laetitia , Saulquin Xavier , Vallette François M. , Vié Henri , Scotet Emmanuel , Pecqueur Claire
Published: September 2019

Purpose:

Cellular immunotherapies are currently being explored to eliminate highly invasive and chemoradioresistant glioblastoma (GBM) cells involved in rapid relapse. We recently showed that concomitant stereotactic injections of nonalloreactive allogeneic Vγ9Vδ2 T lymphocytes eradicate zoledronate-primed human GBM cells. In the present study, we investigated the spontaneous reactivity of allogeneic human Vγ9Vδ2 T lymphocytes toward primary human GBM cells, in vitro and in vivo, in the absence of any prior sensitization.

Experimental Design:

Through functional and transcriptomic analyses, we extensively characterized the immunoreactivity of human Vγ9Vδ2 T lymphocytes against various primary GBM cultures directly derived from patient tumors.

Results:

We evidenced that GBM cells displaying a mesenchymal signature are spontaneously eliminated by allogeneic human Vγ9Vδ2 T lymphocytes, a reactivity process being mediated by γδ T-cell receptor (TCR) and tightly regulated by cellular stress–associated NKG2D pathway. This led to the identification of highly reactive Vγ9Vδ2 T lymphocyte populations, independently of a specific TCR repertoire signature. Moreover, we finally provide evidence of immunotherapeutic efficacy in vivo, in the absence of any prior tumor cell sensitization.

Conclusions:

By identifying pathways implicated in the selective natural recognition of mesenchymal GBM cell subtypes, accounting for 30% of primary diagnosed and 60% of recurrent GBM, our results pave the way for novel targeted cellular immunotherapies.
Cisplatin Facilitates Radiation-Induced Abscopal Effects in Conjunction with PD-1 Checkpoint Blockade Through CXCR3/CXCL10-Mediated T-cell Recruitment
Authors: Luo Ren , Firat Elke , Gaedicke Simone , Guffart Elena , Watanabe Tsubasa , Niedermann Gabriele
Published: September 2019

Purpose:

Localized radiotherapy can cause T-cell–mediated abscopal effects on nonirradiated metastases, particularly in combination with immune checkpoint blockade (ICB). However, results of prospective clinical trials have not met the expectations. We therefore investigated whether additional chemotherapy can enhance radiotherapy-induced abscopal effects in conjunction with ICB.

Experimental Design:

In three different two-tumor mouse models, triple therapy with radiotherapy, anti–PD-1, and cisplatin (one of the most widely used antineoplastic agents) was compared with double or single therapies.

Results:

In these mouse models, the response of the nonirradiated tumor and the survival of the mice were much better upon triple therapy than upon radiotherapy + anti–PD-1 or cisplatin + anti–PD-1 or the monotherapies; complete regression of the nonirradiated tumor was usually only observed in triple-treated mice. Mechanistically, the enhanced abscopal effect required CD8+T cells and relied on the CXCR3/CXCL10 axis. Moreover, CXCL10 was found to be directly induced by cisplatin in the tumor cells. Furthermore, cisplatin-induced CD8+T cells and direct cytoreductive effects of cisplatin also seem to contribute to the enhanced systemic effect. Finally, the results show that the abscopal effect is not precluded by the observed transient radiotherapy-induced lymphopenia.

Conclusions:

This is the first report showing that chemotherapy can enhance radiotherapy-induced abscopal effects in conjunction with ICB. This even applies to cisplatin, which is not classically immunogenic. Whereas previous studies have focused on how to effectively induce tumor-specific T cells, this study highlights that successful attraction of the induced T cells to nonirradiated tumors is also crucial for potent abscopal effects.
Noninvasive Detection of Microsatellite Instability and High Tumor Mutation Burden in Cancer Patients Treated with PD-1 Blockade
Authors: Georgiadis Andrew , Durham Jennifer N. , Keefer Laurel A. , Bartlett Bjarne R. , Zielonka Magdalena , Murphy Derek , White James R. , Lu Steve , Verner Ellen L. , Ruan Finey , Riley David , Anders Robert A. , Gedvilaite Erika , Angiuoli Sam , Jones Siân , Velculescu Victor E. , Le Dung T. , Diaz Luis A. , Sausen Mark
Published: September 2019

Purpose:

Microsatellite instability (MSI) and high tumor mutation burden (TMB-High) are promising pan-tumor biomarkers used to select patients for treatment with immune checkpoint blockade; however, real-time sequencing of unresectable or metastatic solid tumors is often challenging. We report a noninvasive approach for detection of MSI and TMB-High in the circulation of patients.

Experimental Design:

We developed an approach that utilized a hybrid-capture–based 98-kb pan-cancer gene panel, including targeted microsatellite regions. A multifactorial error correction method and a novel peak-finding algorithm were established to identify rare MSI frameshift alleles in cell-free DNA (cfDNA).

Results:

Through analysis of cfDNA derived from a combination of healthy donors and patients with metastatic cancer, the error correction and peak-finding approaches produced a specificity of >99% (n = 163) and sensitivities of 78% (n = 23) and 67% (n = 15), respectively, for MSI and TMB-High. For patients treated with PD-1 blockade, we demonstrated that MSI and TMB-High in pretreatment plasma predicted progression-free survival (hazard ratios: 0.21 and 0.23, P = 0.001 and 0.003, respectively). In addition, we analyzed cfDNA from longitudinally collected plasma samples obtained during therapy to identify patients who achieved durable response to PD-1 blockade.

Conclusions:

These analyses demonstrate the feasibility of noninvasive pan-cancer screening and monitoring of patients who exhibit MSI or TMB-High and have a high likelihood of responding to immune checkpoint blockade.

See related commentary by Wang and Ajani, p. 6887
Polypharmacy Associated with Cognitive Decline in Newly Diagnosed Parkinson’s Disease: A Cross-Sectional Study
Authors: Ishii Nobuyuki , Mochizuki Hitoshi , Sakai Katsuya , Ogawa Go , Shiomi Kazutaka , Nakazato Masamitsu
Published: September 2019

Aims: Polypharmacy is well known to affect cognitive function in community-dwelling older adults. However, the effect of polypharmacy on cognitive function in patients with newly diagnosed Parkinson’s disease remains unknown. Here, we evaluated the association between polypharmacy and cognitive function in patients with newly diagnosed Parkinson’s disease. Methods: This cross-sectional study enrolled 131 consecutive hospitalized patients with newly diagnosed Parkinson’s disease. Cognitive function was evaluated with the Mini-Mental State Examination and analyzed between groups of patients with or without polypharmacy. Comparisons were adjusted for confounders by performing inverse probability weighting with propensity scores. Results: After inverse probability weighting, patients in the polypharmacy group had a significantly lower Mini-Mental State Examination score than patients in the nonpolypharmacy group (26.2 vs. 27.7, p = 0.001). Conclusion: Polypharmacy was associated with cognitive decline in patients with newly diagnosed Parkinson’s disease. This finding suggests that medication reduction might serve as a promising intervention to prevent the development of dementia in patients with early Parkinson’s disease. Further prospective studies are needed to determine whether medication reduction improves cognitive function in patients with newly diagnosed Parkinson’s disease.
Creating Hybrid Monovision with 7.0 mm XL Optic and High-Add AMD Intraocular Lenses (XL-MAGS) in a Patient with Retinitis Pigmentosa
Authors: Borkenstein Andreas F. , Borkenstein Eva-Maria
Published: September 2019

We report a case of a patient with progressed retinitis pigmentosa (RP) who underwent bilateral cataract extraction with implantation of a monofocal enlarged optic in the far dominant eye and a high-add AMD intraocular lens (IOL) in the near dominant eye (hybrid monovision XL-MAGS). A 71-year-old woman presented to our clinic complaining of reduced visual acuity additionally to her diagnosis of RP. The high-add IOL LENTIS® MAX LS-313 MF80 (Oculentis, Germany) was implanted in the right eye and the 7.0 mm optic ASPIRA-aXA IOL (HumanOptics, Germany) in the left eye. Six months postoperatively, the uncorrected distance visual acuity improved from hand motion to 0.5 logMAR in the right eye and to 0.3 logMAR in the left eye. Similarly, best corrected near visual acuity significantly improved to 0.4 and 0.7 logMAR, respectively. The patient’s subjective quality of life and autonomy improved significantly. RP is a severe retinal disease which leads to loss of vision and typical “tunnel vision” with visual field defects. As this genetic disorder is incurable, many ophthalmologists are not willing to perform cataract surgery. However, this case report shows that creating hybrid monovision with a high-add lens and a 7.0 mm optic IOL led to improvement of visual function and, more importantly, enhanced quality of life and self-autonomy of the patient.
Realidades em transformação
Authors: Murrace Thays Bueno
Published: September 2019

Este artigo visa relatar as experiências vividas nos quilombos de Mandira e Ivaporundva – localizados no Vale do Ribeira – durante a excursão didática realizada no curso História da África e dos Afrodescendentes no Brasil: conteúdos e ferramentas didáticas para a formação de professores do Ensino Médio e Fundamental, ministrado pela professora doutora Maria Cristina Cortez Wissenbach,  ao longo do primeiro semestre de 2018, de modo a evidenciar as narrativas construídas acerca da identidade quilombola em cada uma das comunidades e as transformações destas comunidades no tempo.

O Vale do Ribeira contém cerca de oitenta comunidades quilombolas reconhecidas pelo Instituto Palmares, mas que em sua totalidade ainda não receberam a sua titulação. O local apresenta um grande potencial hidrelétrico e mineral, sendo assim alvo de constantes disputas, gerando o Movimento dos Ameaçados por Barragens (MOAB).
A mulher na Inglaterra dos séculos XII a XIV
Authors: Oliveira Jackeline Hernandez Barros
Published: September 2019

A História das mulheres é frequentemente diminuída pelos historiadores, seja por compreendê-la como insignificante ou por fazê-la a partir de uma perspectiva única das relações de poder entre os homens e mulheres; além disso, quando estudada, a História das mulheres costuma ser generalizada, negligenciando suas especificidades e ignorando sua relevãncia para a melhor compreensão do arranjo político e social do período em questão. O presente artigo visa contextualizar e compreender os papéis da mulher na sociedade Inglesa entre os séculos XII à XIV, aplicando a hermenêutica ao poema ABC a Femmes, contido em um manuscrito de grande importância para o período, o MS Harley 2253. Busca-se a partir da fonte compreender o que era esperado dessas mulheres, o que lhes era cobrado e seu nível de autonomia na sociedade.
Mulher negra, trabalho e resistência: Escravizadas, libertas e profissões no século XIX.
Authors: Miranda Karoline Nascimento
Published: September 2019

Esta produção se destina, a partir de uma análise de diversas perspectivas, contribuir para a pesquisa historiográfica acerca das mulheres negras dentro do século XIX, tanto libertas quanto escravas, inseridas no contexto de uma sociedade escravista e suas hierarquizações sociais. O objetivo é contar a história do século XIX do ponto de vista da figura mais baixa da pirâmide social: a mulher negra, resultado da opressão de gênero e de raça, a qual a historiografia é tão parca. Podemos, a partir disso, estudar como eram suas relações sociais e como o trabalho – nosso objeto de estudo no curso – se dava nessas condições.
As representações do movimento de Stonewall nos Estados Unidos (1969)
Authors: Perroni Thaís Cattani , Apolinário Eleonora Beatriz Ramina , Gralak Mariana Mehl , Manfredini Giulia Aniceski , Minatogawa Mayume Christine
Published: September 2019

O início da história da luta por direitos da comunidade LGBT, por vezes, é atribuído às manifestações contra a invasão do bar Stonewall Inn, no episódio que ficou conhecido como “rebelião de Stonewall”. O presente artigo objetiva pensar como se deu a construção da memória sobre o movimento de Stonewall ocorrido na cidade Nova Iorque, em 1969. Além disso, buscamos analisar de que maneira a experiência LGBT estadunidense é representada no cinema. Dessa forma, abordamos o contexto dos Estados Unidos da época, bem como o que foram os protestos de Stonewall e seu impacto para a comunidade LGBT. A questão da memória foi pensada a partir de fontes audiovisuais, com dois longa-metragens, “Stonewall - A Luta pelo Direito de Amar” (1995) e “Stonewall: Onde o Orgulho Começou” (2015), que tiveram diferentes recepções pelo público. Abordamos como esses dois filmes, apesar de tratarem do mesmo ocorrido, possuem narrativas e leituras diferentes sobre a rebelião de Stonewall.