bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced sensitivity forEGFRT790M mutations using the Idylla EGFR Mutation Test
Authors: Lee Eric , Jones Victoria , Topkas Eleni , Harraway James
Published: May 2020

Aims

Osimertinib is a third-generationEGFR(epidermal growth factor receptor) tyrosine kinase inhibitor that is effective in non-small cell lung cancer (NSCLC) harbouring theEGFRT790M mutation. The Idylla EGFR Mutation Test is a rapid cartridge-based method for detecting T790M and otherEGFRmutations. However, false negative T790M results have been reported, and the sensitivity of the assay for this mutation is uncertain.

Methods

Eighty NSCLC samples were tested by both Idylla and a next-generation sequencing (NGS) assay; 46 were from patients at disease progression, and 24 of these had known T790M mutations. Droplet digital PCR (ddPCR) was used to confirm NGS findings in samples with the T790M mutation.

Results

Of 19 samples with T790M variant allele frequencies (VAF) higher than the stated 5% limit of detection, 14 were detected by Idylla (sensitivity 74%, 95% CI 49% to 90%). Where sufficient sample remained, ddPCR was consistent with NGS findings in all samples. False negative T790M results were associated with higherEGFRcontrol Cq values (median 22.8 vs 19.8), presence of theEGFRQ787Q polymorphism in cis (80% vs 44%) and presence of an invalid T790M amplification curve. AnEGFRexon 19 indel with VAF >5% was also not detected by the Idylla assay in two samples.

Conclusions

The Idylla EGFR Mutation Test has reduced sensitivity for the T790M mutation compared with NGS and ddPCR methods. The presence of an invalid T790M amplification curve may indicate a possible false negative result that warrants further testing by an orthogonal method.
Found in translation: navigating uncertainty to save a child's heart. Paediatric cardiac surgery in Cape Town, South Africa
Authors: Vivian Lauraine Margaret Helen , Hunter Cynthia , Tan Lawrence , Comitis George , Neveling Guy , Lawrenson John
Published: May 2020

This medical humanities paper describes our qualitative research into pathways to care and informed consent for 10 children who had cardiac surgery in the Red Cross War Memorial Children’s Hospital, Cape Town, South Africa. Our multidisciplinary team consists of cardiologists, anthropologists, a social scientist and a general practitioner in two sites, South Africa and Australia. This paper builds on our first publication in a specialist cardiology journal on a ‘qualitative snapshot’ of these children’s life stories from 2011 to 2016 but turns to the medical humanities to explore a concept of ‘uncertainty’. Data analysis revealed that for the children’s parents and doctors, ‘uncertainty’ underscored procedures. Indeed, the literature review showed that ‘uncertainty’ is intrinsic to heart surgery and was integral to Barnard’s first heart transplant in Cape Town in 1967. We demonstrate that in meeting the challenges inherent in the ‘uncertainty dimension’, doctors established greater ‘medical certainty’about each operation. This happened as they encountered the difficult clinical and biopsychosocial factors that were fundamental to the diagnosis of children’s cardiac defects. It was doctors’ translation of these decision-making processes that informed parental decisions and described why, despite feelings of uncertainty, parents signed consent. To visually describe heart surgery in this locality we asked the South African photographer, Guy Neveling to record some children undergoing echocardiograms and surgery. These photographs qualitatively demonstrate what medical certainty entails, and parents’ trust in doctors and surgeons, whom they knew had ‘reasonable certainty’ that their child’s‘heart is worth saving’.
The use of an object: exploring physician burnout through object relations theory
Authors: Winning Jo
Published: May 2020

The crisis of physician burnout has been widely and repeatedly reported across the mainstream press and medical journals around the world, in the closing years of the second decade of the 21st century. Despite multiple systematic reviews and commentary on the scale of this ‘global epidemic’, understandings of both the phenomenon and the most effective interventions remain limited. Practice-based medical humanities represents the collaborative sharing of conceptual tools for understanding illness and clinical practice and the shouldering of responsibility for mapping the shape of care, in all its local, national and global contexts, thinking-with rather than critique on the profession and its practices. In keeping with this approach, this article offers a new perspective on the contemporary crisis of physician burnout by exploring the objectification of the clinician’s body within the systems and practice of healthcare. Within the context of medical humanities’ scholarship, discussions of objectification usually navigate towards a discussion about patient identity and its potentially reductive objectification within the frameworks of biomedical science. However, this article crosses the cultural divide between clinician and patient, and comes to focus on the objectification of the clinician herself, using object relations theory from the field of psychoanalysis to excavate the psychodynamics of care and their impact on clinicians, and the systems of healthcare in which care is delivered.
Sphingolipid, fatty acid and phospholipid metabolites are associated with disease severity and mTOR inhibition in lymphangioleiomyomatosis
Authors: Bottolo Leonardo , Miller Suzanne , Johnson Simon R
Published: May 2020

Background

Lymphangioleiomyomatosis (LAM) is a rare multisystem disease almost exclusively affecting women which causes loss of lung function, lymphatic abnormalities and angiomyolipomas. LAM occurs sporadically and in people with tuberous sclerosis complex (TSC). Loss ofTSCgene function leads to dysregulated mechanistic target of rapamycin (mTOR) signalling. As mTOR is a regulator of lipid and nucleotide synthesis, we hypothesised that the serum metabolome would be altered in LAM and related to disease severity and activity.

Methods

Ultrahigh performance liquid chromatography-tandem mass spectroscopy was used to examine the serum metabolome of 79 closely phenotyped women with LAM, including 29 receiving treatment with an mTOR inhibitor and 43 healthy control women.

Results

Sphingolipid, fatty acid and phospholipid metabolites were associated with FEV1in women with LAM (eg, behenoyl sphingomyelin adjusted (adj.) p=8.10 × 10-3). Those with higher disease-burden scores had abnormalities in fatty acid, phospholipid and lysolipids. Rate of loss of FEV1was associated with differences in acyl-carnitine, acyl-glycines, acyl-glutamine, fatty acids, endocanbinoids and sphingolipids (eg, myristoleoylcarnitine adj. p=0.07). In TSC-LAM, rapamycin affected modules of interrelated metabolites which comprised linoleic acid, the tricarboxylic acid cycle, aminoacyl-tRNA biosynthesis, cysteine, methionine, arginine and proline metabolism. Metabolomic pathway analysis within modules reiterated the importance of glycerophospholipid metabolites (adj. p=0.047).

Conclusions

Women with LAM have altered lipid metabolism. The associations between these metabolites, multiple markers of disease activity and their potential biological roles in cell survival and signalling, suggest that lipid species may be both disease-relevant biomarkers and potential therapeutic targets for LAM.
Particle depletion of diesel exhaust restores allergen-induced lung-protective surfactant protein D in human lungs
Authors: Ryu Min Hyung , Lau Kevin Soon-Keen , Wooding Denise Jill , Fan Shuyu , Sin Don D , Carlsten Christopher
Published: May 2020

Rationale

Exposure to air pollution is linked with increased asthma morbidity and mortality. To understand pathological processes linking air pollution and allergen exposures to asthma pathophysiology, we investigated the effect of coexposure to diesel exhaust (DE) and aeroallergen on immune regulatory proteins in human airways.

Methods

Fourteen allergen-sensitised participants completed this randomised, double-blinded, cross-over, controlled exposure study. Each participant underwent four exposures (allergen-alone exposure, DE and allergen coexposure, particle-depleted DE (PDDE) and allergen coexposure, and sham exposure) on different order-randomised dates, each separated by a 4-week washout. Serum and bronchoalveolar lavage (BAL) were assayed for pattern recognition molecules, cytokines, chemokines and inflammatory mediators.

Results

In human airways, allergen-alone exposure led to accumulation of surfactant protein D (SPD; p=0.02). Coexposure to allergen and DE did not elicit the same increase of SPD as did allergen alone; diesel particulate reduction restored allergen-induced SPD accumulation. Soluble receptor for advanced glycation end products was higher with particle reduction than without it. In the systemic circulation, there was a transient increase in SPD and club cell protein 16 (CC16) 4 hours after allergen alone. CC16 was augmented by PDDE, but not DE. % eosinophils in BAL (p<0.005), eotaxin-3 (p<0.0001), interleukin 5 (IL-5; p<0.0001) and thymus and activation regulated chemokine (p=0.0001) were each increased in BAL by allergen. IL-5, SPD and % eosinophils in BAL were correlated with decreased FEV1.

Conclusion

Short-term coexposure to aeroallergen and DE alters immune regulatory proteins in lungs; surfactant levels are dependent on particle depletion.

Trial registration number

NCT02017431.
COVID-19: in the footsteps of Ernest Shackleton
Authors: Ing Alvin J , Cocks Christine , Green Jeffery Peter
Published: May 2020

We describe what we believe is the first instance of complete COVID-19 testing of all passengers and crew on an isolated cruise ship during the current COVID-19 pandemic. Of the 217 passengers and crew on board, 128 tested positive for COVID-19 on reverse transcription–PCR (59%). Of the COVID-19-positive patients, 19% (24) were symptomatic; 6.2% (8) required medical evacuation; 3.1% (4) were intubated and ventilated; and the mortality was 0.8% (1). The majority of COVID-19-positive patients were asymptomatic (81%, 104 patients). We conclude that the prevalence of COVID-19 on affected cruise ships is likely to be significantly underestimated, and strategies are needed to assess and monitor all passengers to prevent community transmission after disembarkation.
Ultrasound‐guided epidural nerve block in a domestic dwarf rabbit (Oryctolagus cuniculus) undergoing ovariohysterectomy
Authors: Medina Serra Roger , Dominguez Sheyla , Vilalta Laura , Palacios Carolina
Published: May 2020

A healthy 2‐year‐old entire female domestic dwarf rabbit (Oryctolagus cuniculus) was referred for ovariohysterectomy. The premedication included subcutaneous 3 mg/kg ketamine, 1 mg/kg midazolam and 0.05 mg/kg medetomidine. A CT scan was performed under sedation to assess the lumbosacral region. Anaesthesia was induced with propofol (total dose of 10 mg/kg) and maintained with isoflurane in a mixture of oxygen and medical air administered through a supraglottic airway device. Under anaesthesia and prior to the ovariohysterectomy, an ultrasound‐guided epidural was performed administering 0.1 mg/kg preservative free morphine and 0.35 per cent (2.4 mg/kg) bupivacaine as part of the multimodal analgesic approach. Haemodynamic stability with no signs of hypotension, bradycardia or hypoventilation were observed under anaesthesia. Meloxicam (0.5 mg/kg) and buprenorphine (0.03 mg/kg) were administered during the postoperative period. A smooth and uneventful anaesthesia, recovery and hospitalisation period were achieved. Ultrasound‐guided epidural administration of drugs could be applied in similar cases.
Low-bandgap push–pull molecules in polymer matrices for use in thin-film organic photovoltaic devices
Authors: Brunner Pierre-Louis M. , Beaudoin Daniel , Heskia Alice , Maris Thierry , Dubois Marc-André , Wuest James D.
Published: May 2020

Conjugated polymers are widely used in thin-film organic photovoltaic devices to absorb light and serve as electron donors or acceptors. Small molecular analogues are attractive substitutes because they have fully defined structures, can be purified rigorously, and are typically more soluble and volatile. However, producing active films composed primarily of small molecules remains challenging. We have devised bulk heterojunction solar cells in which poly(3-hexylthiophene-2,5-diyl) and poly[[9-(1-octylnonyl)-9H-carbazole-2,7-diyl]-2,5-thiophenediyl-2,1,3-benzothiadiazole-4,7-diyl-2,5-thiophenediyl] are used as matrices to prepare films containing low-bandgap push–pull molecules as electron donors and (6,6)-phenyl-C61-butyric acid methyl ester or (6,6)-phenyl-C71-butyric acid methyl ester as electron acceptors. Compared with reference devices devoid of push–pull molecular additives, increases in power conversion efficiencies up to 30.4% were measured.
Molecular-frame (e, 2e) ionization dynamics of H2 at high impact-energy
Authors: Wang Enliang , Ali Esam , Li Xingyu , Ren Xueguang , Chen Xiangjun , Madison Don , Dorn Alexander
Published: May 2020

We report a combined experimental and theoretical study on the electron-impact ionization dynamics of H2 at an impact-energy of 520 eV. The molecular-frame fivefold-differential cross sections were measured for electron emission in the plane perpendicular to the incoming projectile beam. An (e, 2e + ion) triple coincidence method was used covering projectile scattering angles of 6.5°, 10.0° and 20.0° and ejected energies of 20 eV and 30 eV. The experimental cross sections are compared with results from the multi-center distorted-wave (MCDW) as well as the molecular three-body distorted wave (M3DW) approaches. M3DW is in overall better agreement with the measured data in the binary lobes than MCDW, while the intensity of recoil lobes are underestimated by both theories. Furthermore, we examine the presence of two-center interference patterns by comparing the experimental cross section ratios between mutually perpendicular alignment angles of the molecular axis with that predicated by the interference model. Agreement with the interference model is found only for Bethe ridge kinematics, i.e. in the binary peak region and with the ejected electron momentum being roughly equal to the momentum transfer. Finally, we suggest a modified interference formula for the recoil peak which takes into account the backscattering of the ejected electron in the ionic potential.

Graphical abstract
Charles Galton Darwin’s 1922 quantum theory of optical dispersion
Authors: Johnson Benjamin
Published: May 2020

The quantum theory of dispersion was an important conceptual advancement which led out of the crisis of the old quantum theory in the early 1920s and aided in the formulation of matrix mechanics in 1925. The theory of Charles Galton Darwin, often cited only for its reliance on the statistical conservation of energy, was a wave-based attempt to explain dispersion phenomena at a time between the theories of Ladenburg and Kramers. It contributed to future successes in quantum theory, such as the virtual oscillator, while revealing through its own shortcomings the limitations of the wave theory of light in the interaction of light and matter. After its publication, Darwin’s theory was widely discussed amongst his colleagues as the competing interpretation to Compton’s in X-ray scattering experiments. It also had a pronounced influence on John C. Slater, whose ideas formed the basis of the BKS theory.
Enhancement of Hippocampal Spatial Decoding Using a Dynamic Q-Learning Method With a Relative Reward Using Theta Phase Precession
Authors: Chen Bo-Wei , Yang Shih-Hung , Lo Yu-Chun , Wang Ching-Fu , Wang Han-Lin , Hsu Chen-Yang , Kuo Yun-Ting , Chen Jung-Chen , Lin Sheng-Huang , Pan Han-Chi , Lee Sheng-Wei , Yu Xiao , Qu Boyi , Kuo Chao-Hung , Chen You-Yin , Lai Hsin-Yi
Published: May 2020

Hippocampal place cells and interneurons in mammals have stable place fields and theta phase precession profiles that encode spatial environmental information. Hippocampal CA1 neurons can represent the animal’s location and prospective information about the goal location. Reinforcement learning (RL) algorithms such as Q-learning have been used to build the navigation models. However, the traditional Q-learning ([Formula: see text]Q-learning) limits the reward function once the animals arrive at the goal location, leading to unsatisfactory location accuracy and convergence rates. Therefore, we proposed a revised version of the Q-learning algorithm, dynamical Q-learning ([Formula: see text]Q-learning), which assigns the reward function adaptively to improve the decoding performance. Firing rate was the input of the neural network of [Formula: see text]Q-learning and was used to predict the movement direction. On the other hand, phase precession was the input of the reward function to update the weights of [Formula: see text]Q-learning. Trajectory predictions using [Formula: see text]Q- and [Formula: see text]Q-learning were compared by the root mean squared error (RMSE) between the actual and predicted rat trajectories. Using [Formula: see text]Q-learning, significantly higher prediction accuracy and faster convergence rate were obtained compared with [Formula: see text]Q-learning in all cell types. Moreover, combining place cells and interneurons with theta phase precession improved the convergence rate and prediction accuracy. The proposed [Formula: see text]Q-learning algorithm is a quick and more accurate method to perform trajectory reconstruction and prediction.
Projectile breakup effects in the fusion dynamics of 6,7Li +144,152Sm reactions around Coulomb barrier
Authors: Gautam Manjeet Singh , Duhan Sukhvinder , Chahal Rishi Pal , Khatri Hitender , Kuhar Suman B. , Vinod K.
Published: May 2020

This work emphasized the role of the projectile breakup channel by studying the complete fusion (CF) and incomplete fusion (ICF) dynamics of [Formula: see text] reactions. The theoretical calculations for the chosen reactions have been done by opting for the coupled channel approach and the energy dependent Woods–Saxon potential (EDWSP) model. The below barrier fusion enhancements of the studied reactions are reasonably addressed by the outcomes of the adopted models, which in turn can be attributed to the couplings of nuclear structure degrees of freedom of the collision partners to their relative motion. In contrast, at above barrier energies, the CF cross-section data of the chosen reactions are found to be suppressed significantly when compared with the predictions made by using the present models. Interestingly, the fusion suppression factors of the given reactions can be minimized considerably with respect to the reported value when it is analyzed within the framework of the EDWSP model. For instance, in case of [Formula: see text] ([Formula: see text] reaction, the magnitude of fusion suppression factor is minimized up to 7% (13%) relative to the reported value whereas for [Formula: see text] ([Formula: see text] reaction, the fusion suppression factor is found to be less by 7% (8%) with reference to the reported value. Such suppression effects can be correlated with the low breakup threshold of alpha breakup channel associated with the loosely bound projectile. The projectiles being weakly bound systems split into two charged fragments and either of the breakup components is absorbed by the target resulting in the reduction of incoming flux going into fusion channel. The flux lost from the CF channel appears in the form of ICF yields. For [Formula: see text], total fusion (TF) cross-sections that are sum of CF and ICF cross-sections are also analyzed in conjunction with the EDWSP model and thus reasonably explained by the model calculations. In order to identify the ICF contribution, the ratio of ICF/TF cross-section data of [Formula: see text] reaction has been examined and thus properly addressed by using the EDWSP model. The presence of ICF component in TF cross-section clearly pointed out the breakup of projectile due to its loosely bound nature prior to the Coulomb barrier. Although ICF data of other systems are not available in the literature, a similar behavior is expected for ICF and TF data for [Formula: see text] and [Formula: see text] reactions.
The Sureste Basin of Mexico: its framework, future oil exploration opportunities and key challenges ahead
Authors: Shann Mark V.
Published: May 2020

The Sureste Basin of Mexico is a story of split exploration maturity, with more than 139 discoveries in the onshore and shallow-water area of the Sureste in a series of stacked prolific plays, but less than 12 exploration wildcat wells on the Campeche slope, in water depths greater than 500 m. Over 50% of the basin area lies in this under-explored deep-water Campeche slope, with future oil potential shown by the presence of wide seabed oil seepage indicating a regionally mature world-class source rock to be present. With the 2014 opening of Mexico's oil industry, basin-wide 3D seismic imaging of this under-explored deep-water extension to the Sureste Basin is now in the hands of international oil companies that hold substantial exploration well commitments over the next few years. This paper discusses the hydrocarbon play potential of both the classic Tertiary slope clastic reservoir systems as well as the significant Mesozoic carbonate reservoir potential for which there are fewer analogues outside of Mexico.

Subsurface challenges originating from dry hole analysis relate to charge timing and deep charge focus, subsalt deep structural imaging, deep reservoir quality issues and uncertainty in column height prediction, given the high-relief nature of many undrilled salt related structures.
Palaeogeographical reconstruction and provenance of Oxfordian aeolian sandstone reservoirs in Mexico offshore areas: comparison to the Norphlet aeolian system of the northern Gulf of Mexico
Authors: Snedden John W. , Stockli D. F. , Norton I. O.
Published: May 2020

Palaeogeographical reconstruction of the Oxfordian-age (Jurassic) depositional systems in the southern Gulf of Mexico is supported by detailed sedimentological analyses, detrital zircon geothermochronology and plate tectonic restorations. This integrated approach departs from prior local studies by placing the Bacab Sandstone, a major reservoir in offshore Mexico, in a larger basin- to regional-scale context.

Sedimentary characteristics derived from detailed core description show how remarkably similar the Bacab Sandstone is to coeval sandstones of the Norphlet Formation of the northern Gulf of Mexico. A comparison of lithofacies associations suggests similar depositional processes and palaeoclimate regimes, with aeolian dunes forming near base level with adequate wind, sediment supply and arid climatic conditions promoting development of dunes and adjacent sabhkas. Construction of prominent ergs (aeolian sand seas) with lateral transitions to updip fluvial–wadi systems is envisioned in Mexico, comparable to the Norphlet of the northern Gulf of Mexico.

Reservoir quality over the southern Mexican offshore area is variable, as numerous well penetrations over several decades have demonstrated. However, in the core area of the Ek-Balam Field, the best reservoirs have surprisingly good porosity and permeability for their age (Jurassic) and present-day depth of burial (>4000 m). However, published information is not definitive on the factors mitigating subsurface reservoir quality destruction. It is possible that similar processes preserving or enhancing porosity under deep burial conditions for the Norphlet are likely to have operated in the Ek and Balam well locations.

Available petrographical data on framework grains are similar for Oxfordian sandstones in both the northern and southern Gulf of Mexico. Detrital zircon U–Pb geochronology, however, indicates that different source terranes supplied clastics to the Oxfordian Bacab and Norphlet sandstones. Detrital zircon geothermochronology age spectra indicate that the Mayan (Yucatán) Block was the primary terrane for the Bacab Sandstone. This is separate and distinct from Norphlet source areas that vary from Appalachian (Laurentian) to Pan-African (Gondwanan and peri-Gondwanan) terranes. While it possible that the Bacab and Norphlet sandstones were continuous and connected across the Yucatán margin that lies between the two areas, detrital zircon provenance results do not show any indication of common source terranes. Dimensional considerations, such as the contrasting ratios of Bacab and Norphlet source areas to their respective documented areas of deposition, also support the notion of separated aeolian palaeoenvironments.
Under the Concealing Surface: Detecting and Understanding Live Webcams in the Wild
Authors: Song JinKe , Li Qiang , Wang Haining , Sun Limin
Published: May 2020

Given the central role of webcams in monitoring physical surroundings, it behooves the research community to understand the characteristics of webcams' distribution and their privacy/security implications. In this paper, we conduct the first systematic study on live webcams from both aggregation sites and individual webcams (webpages/IP hosts). We propose a series of efficient, automated techniques for detecting and fingerprinting live webcams. In particular, we leverage distributed algorithms to detect aggregation sites and generate webcam fingerprints by utilizing the Graphical User Interface (GUI) of the built-in web server of a device. Overall, we observe 0.85 million webpages from aggregation sites hosting live webcams and 2.2 million live webcams in the public IPv4 space. Our study reveals that aggregation sites have a typical long-tail distribution in hosting live streams (5.8% of sites contain 90.44% of live streaming contents), and 85.4% of aggregation websites scrape webcams from others. Further, we observe that (1) 277,239 webcams from aggregation sites and IP hosts (11.7%) directly expose live streams to the public, (2) aggregation sites expose 187,897 geolocation names and more detailed 23,083 longitude/latitude pairs of webcams, (3) the default usernames and passwords of 38,942 webcams are visible on aggregation sites in plaintext, and (4) 1,237 webcams are detected as having been compromised to conduct malicious behaviors.
Optimal Data Placement for Heterogeneous Cache, Memory, and Storage Systems
Authors: Zhang Lei , Karimi Reza , Ahmad Irfan , Vigfusson Ymir
Published: May 2020

New memory technologies are blurring the previously distinctive performance characteristics of adjacent layers in the memory hierarchy. No longer are such layers orders of magnitude different in request latency or capacity. Beyond the traditional single-layer view of caching, we now must re-cast the problem as a data placement challenge: which data should be cached in faster memory if it could instead be served directly from slower memory? We present CHOPT, an offline algorithm for data placement across multiple tiers of memory with asymmetric read and write costs. We show that CHOPT is optimal and can therefore serve as the upper bound of performance gain for any data placement algorithm. We also demonstrate an approximation of CHOPT which makes its execution time for long traces practical using spatial sampling of requests incurring a small 0.2% average error on representative workloads at a sampling ratio of 1%. Our evaluation of CHOPT on more than 30 production traces and benchmarks shows that optimal data placement decisions could improve average request latency by 8.2%-44.8% when compared with the long-established gold standard: Belady and Mattson's offline, evict-farthest-in-the-future optimal algorithms. Our results identify substantial improvement opportunities for future online memory management research.
Online Linear Optimization with Inventory Management Constraints
Authors: Yang Lin , Hajiesmaili Mohammad H. , Sitaraman Ramesh , Wierman Adam , Mallada Enrique , Wong Wing S.
Published: May 2020

This paper considers the problem of online linear optimization with inventory management constraints. Specifically, we consider an online scenario where a decision maker needs to satisfy her time-varying demand for some units of an asset, either from a market with a time-varying price or from her own inventory. In each time slot, the decision maker is presented a (linear) price and must immediately decide the amount to purchase for covering the demand and/or for storing in the inventory for future use. The inventory has a limited capacity and can be used to buy and store assets at low price and cover the demand when the price is high. The ultimate goal of the decision maker is to cover the demand at each time slot while minimizing the cost of buying assets from the market. We propose ARP, an online algorithm for linear programming with inventory constraints, and ARPRate, an extended version that handles rate constraints to/from the inventory. Both ARP and ARPRate achieve optimal competitive ratios, meaning that no other online algorithm can achieve a better theoretical guarantee. To illustrate the results, we use the proposed algorithms in a case study focused on energy procurement and storage management strategies for data centers.
Fiedler Vector Approximation via Interacting Random Walks
Authors: Doshi Vishwaraj , Eun Do Young
Published: May 2020

The Fiedler vector of a graph, namely the eigenvector corresponding to the second smallest eigenvalue of a graph Laplacian matrix, plays an important role in spectral graph theory with applications in problems such as graph bi-partitioning and envelope reduction. Algorithms designed to estimate this quantity usually rely on a priori knowledge of the entire graph, and employ techniques such as graph sparsification and power iterations, which have obvious shortcomings in cases where the graph is unknown, or changing dynamically. In this paper, we develop a framework in which we construct a stochastic process based on a set of interacting random walks on a graph and show that a suitably scaled version of our stochastic process converges to the Fiedler vector for a sufficiently large number of walks. Like other techniques based on exploratory random walks and on-the-fly computations, such as Markov Chain Monte Carlo (MCMC), our algorithm overcomes challenges typically faced by power iteration based approaches. But, unlike any existing random walk based method such as MCMCs where the focus is on the leading eigenvector, our framework with interacting random walks converges to the Fiedler vector (second eigenvector). We also provide numerical results to confirm our theoretical findings on different graphs, and show that our algorithm performs well over a wide range of parameters and the number of random walks. Simulations results over time varying dynamic graphs are also provided to show the efficacy of our random walk based technique in such settings. As an important contribution, we extend our results and show that our framework is applicable for approximating not just the Fiedler vector of graph Laplacians, but also the second eigenvector of any time reversible Markov Chain kernel via interacting random walks. To the best of our knowledge, our attempt to approximate the second eigenvector of any time reversible Markov Chain using random walks is the first of its kind, opening up possibilities to achieving approximations of higher level eigenvectors using random walks on graphs.
microRNA-382 suppresses the progression of pancreatic cancer through the PI3K/Akt signaling pathway by inhibition of Anxa3
Authors: Wan Xiaohui , Guo Dongrui , Zhu Qi , Qu Rongfeng
Published: May 2020

This study focused on the mechanism of miR-382 in epithelial mesenchymal transition and lymph node metastasis in PC in relation to Anxa3 and the PI3K/Akt signaling pathway. We found the inhibitory role of miR-382 in PC in vitro and in vivo.
Biocurcumin as Radiosensitiser for Cervical Cancer Study (BRACES): A Double‐Blind Randomised Placebo‐Controlled Trial
Authors: Purbadi Sigit , Rustamadji Primariadewi , Prijanti Ani R. , Sekarutami Sri M. , Sutrisna Bambang , Suyatna Franciscus D. , Andrijono
Published: May 2020

Cervical cancer is a leading cause of death among women worldwide, particularly in Indonesia. The main treatment of advanced‐stage cervical cancer is radiation; however, the outcomes do not meet the required expectations. [1,7‐Bis(4‐hydroxy‐3‐methoxyphenyl)‐1,6‐heptadiene‐3,5dione] has been reported in several studies for its potency in cancer therapy. This study aims to investigate the clinical and molecular [(malondialdehyde (MDA) and NF‐κB levels] effects, apoptotic index, and safety of Biocurcumin (BCM‐95) as a radiosensitiser in cervical cancer. In this double‐blind placebo randomised‐controlled trial, we randomised 121 patients into 2 groups (BCM‐95 or placebo). MDA and their NF‐κB levels and apoptotic index were measured before and after administering 24 Gy of radiation. MDA was identified using Wills’ method, whereas NF‐κB was identified via ELISA. The apoptotic index was identified using TUNEL and DAPI staining. The clinical response was classified based on the RECIST. MDA levels before radiation were similar between both groups in per protocol and intention‐to‐treat (ITT) analyses (p = 0.53 and p = 0.16, respectively). After radiation, MDA levels increased in both groups with no significant differences in per protocol and ITT analyses (p = 0.52 and p = 0.18, respectively). NF‐κB levels before radiation were similar between the two groups in per protocol and ITT analyses (p = 0.92 and p = 0.98, respectively). After radiation, the BCM‐95 group showed an increase in the NF‐κB levels compared with the placebo group in per protocol analysis but not in ITT analysis (p = 0.018 and p = 0.42, respectively). The BCM‐95 group had a higher apoptotic index before radiation in per protocol analysis but not in ITT analysis (p = 0.01 and p = 0.61, respectively). After radiation, the apoptotic index remained higher in the BCM‐95 group in per protocol analysis but not in ITT analysis (p = 0.04 and p = 0.91, respectively). There was no significant difference in complete response between the groups (per protocol, p = 0.61; ITT analysis, p = 0.90). Although BCM‐95 can regulate ROS, NF‐κB, and apoptosis in human cervical cancer, it is not significant. Therefore, BCM‐95 does not improve clinical response to radiation treatment.
Game-Theoretic Models of Green Products in a Two-Echelon Dual-Channel Supply Chain under Government Subsidies
Authors: Lou Zhenkai , Lou Xuming , Dai Xiaozhen
Published: May 2020

This paper deals with issues concerning green subsidies of government and optimal decisions of a manufacture and dual-channel retailers in a two-echelon dual-channel supply chain. Both a decentralized supply chain and a centralized supply chain are considered. Sufficient and necessary conditions for guaranteeing that the two supply chains run normally under government subsidies are proposed. For the decentralized supply chain, a three-layer model is constructed according to different priorities of the four participants. Both Bertrand game and Stackelberg game are involved. For the centralized supply chain, a two-layer model is given. Decision models of the government under a financial budget are developed for maximizing the green degree of each case. It is shown that the green degree of the product of the centralized supply chain is always higher than that of the decentralized supply chain. Meanwhile, the total profit of the centralized supply is also higher. Finally, a numerical illustration is presented to visualize the discussed models and make some supplements.
Aging Process of Cadmium, Copper, and Lead under Different Temperatures and Water Contents in Two Typical Soils of China
Authors: Liu Guannan , Yu Zhanqiu , Liu Xinhui , Xue Wei , Dong Liming , Liu Yongbing
Published: May 2020

Aging process of exogenous heavy metals in soil is significant for reducing their environmental risk due to the redistribution of species of soil heavy metals. A red soil (ultisol) and a brown soil (alfisol) were selected to investigate the aging process of cadmium (Cd), copper (Cu), and lead (Pb) under different regimes of temperature and water content. Most introduced heavy metals were all transformed from dissolved fraction to more stable fractions within 5 days of incubation. During incubation, most Pb existed in the fraction bound to Fe/Mn oxides, while exchangeable and carbonate-associated fraction was the dominant portion for Cd and Cu, suggesting that the transformation rate followed the order: Pb > Cu > Cd. The exchangeable and carbonate-associated fraction in red soil, which was characterized with higher pH and Fe/Al/Mn oxides and lower organic matter (OM), was significantly higher than that in brown soil, implying that soil OM was the important factor affecting the aging process of soil heavy metals in the present study. In addition, increases of temperature and soil water content can accelerate the transformation of most introduced Cd, Cu, and Pb to more stable forms in the soils. The results indicated that soil properties, environmental factors (i.e., temperature and water content), types of heavy metals, and pollution time can significantly affect the aging process of exogenous heavy metals.
Stereotactic Body Radiotherapy as a Salvage Therapy after Incomplete Radiofrequency Ablation for Hepatocellular Carcinoma: A Retrospective Cohort Study
Authors: Fu Yizhen , Xi Mian , Pan Yangxun , Chen Jinbin , Wang Juncheng , Liu Shiliang , Xu Li , Zhou Zhongguo , Liu Mengzhong , Chen Minshan , Zhao Lei , Zhang Yaojun
Published: May 2020

Residual tumor tissue after radiofrequency ablation (RFA) is inevitable in clinical practice, and the optimal management of residual tumor after RFA has not been established. To evaluate the efficiency and toxicity of stereotactic body radiotherapy (SBRT) as a salvage therapy after incomplete RFA for hepatocellular carcinoma (HCC), we retrospectively included 32 HCC patients with an initial incomplete response (iIR) to RFA from May 2011 to August 2018. An iIR was defined as the presence of residual enhancement on CT or MRI one month after RFA treatment. The primary endpoint was local tumor control (LTC); the secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. All patients fulfilled 6 fractions of SBRT as planned, with dosages ranging from 30 Gy to 54 Gy. The objective response rate (ORR) was 50.0%. The 1- and 2-year LTC rates were 86.6% (95% CI, 74.3% to 98.9%) and 74.7% (95% CI, 55.9% to 93.5%), respectively. Fewer times of prior treatments was associated with better LTC (HR = 11.7, P=0.026). The 1- and 2-year PFS rate were 69.9% (95% CI, 53.4% to 86.4%) and 52.7% (95% CI, 33.1% to 72.3%), respectively. A higher Child-Pugh score was the only independent risk factor for tumor progression (HR = 5.17, P=0.012). The 1- and 3-year OS rate were 85.6% and 67.1%, respectively. Only two patients suffered grade 3 adverse events, and none experienced grade 4 or 5 events. In conclusion, for HCC patients confirmed to have an iIR to prior RFA, with compensated liver function, SBRT provided favorable LTC and OS along with acceptable toxicity.
Experiment and Analysis of Wedge Cutting Angle on Cutting Effect
Authors: Yang Deqiang , Wang Xuguang , Wang Yinjun , An Huaming , Lei Zhen
Published: May 2020

In the process of tunnel excavation, large charge wedge cutting blasting is widely used to improve the effect of cut blasting and speed up the excavation rate, which is tantamount to increasing the construction cost. In order to save economic cost and improve cutting blasting effect, wedge cutting models with five different cutting angles were experimented and studied by using concrete materials on the basis of similarity theory analysis. The relationships among cutting depth, blasting volume, blasting fragment, and cutting angle are studied and deduced by the dimensional analysis method. The polynomial fitting of cutting depth, blasting volume, blasting fragment, and cutting angle is carried out according to the experimental data, and the corresponding fitting formula is obtained. The optimum cutting depth, hole utilization rate, blasting volume, and blasting fragment were obtained when the wedge cutting angle was 67° under the same charge. The values were 1.665 × 10−1 m, 92.5%, 8.390 × 10−3 m3, and 49.07 mm, respectively. With the use of TC4850N type blasting vibration meter, the blasting vibrations on the wedge in four directions are tested and analyzed. The results show that when wedge cutting inclination is 65 degrees, the peak vibration velocity is the minimum and the vibration intensity of the wedge cutting inclined side is generally smaller than that of the vertical side. Considering the cutting depth, blasting volume, blasting fragment, blasting vibration hazard, drilling error, tunneling construction cost, and other factors, the 65°∼69° wedge cutting blasting in engineering practice can improve the blasting tunneling rate and increase economic benefits. The experimental results show that the blasting tunneling rate is increased and the economic benefit is increased with the minimum construction tunneling cost, which has certain engineering significance.
Adaptive Hybrid Soft-Sensor Model of Grinding Process Based on Regularized Extreme Learning Machine and Least Squares Support Vector Machine Optimized by Golden Sine Harris Hawk Optimization Algorithm
Authors: Xie Wei , Wang Jie-sheng , Xing Cheng , Guo Sha-Sha , Guo Meng-wei , Zhu Ling-feng
Published: May 2020

Soft-sensor technology plays a vital role in tracking and monitoring the key production indicators of the grinding and classifying process. Least squares support vector machine (LSSVM), as a soft-sensor model with strong generalization ability, can be used to predict key production indicators in complex grinding processes. The traditional crossvalidation method cannot obtain the ideal structure parameters of LSSVM. In order to improve the prediction accuracy of LSSVM, a golden sine Harris Hawk optimization (GSHHO) algorithm was proposed to optimize the structure parameters of LSSVM models with linear kernel, sigmoid kernel, polynomial kernel, and radial basis kernel, and the influences of GSHHO algorithm on the prediction accuracy under these LSSVM models were studied. In order to deal with the problem that the prediction accuracy of the model decreases due to changes of industrial status, this paper adopts moving window (MW) strategy to adaptively revise the LSSVM (MW-LSSVM), which greatly improves the prediction accuracy of the LSSVM. The prediction accuracy of the regularized extreme learning machine with MW strategy (MW-RELM) is higher than that of MW-LSSVM at some moments. Based on the training errors of LSSVM and RELM within the window, this paper proposes an adaptive hybrid soft-sensing model that switches between LSSVM and RELM. Compared with the previous MW-LSSVM, MW-neural network trained with extended Kalman filter(MW-KNN), and MW-RELM, the prediction accuracy of the hybrid model is further improved. Simulation results show that the proposed hybrid adaptive soft-sensor model has good generalization ability and prediction accuracy.
DNA Replication Stress Induced by Trifluridine Determines Tumor Cell Fate According to p53 Status
Authors: Kataoka Yuki , Iimori Makoto , Fujisawa Ryo , Morikawa-Ichinose Tomomi , Niimi Shinichiro , Wakasa Takeshi , Saeki Hiroshi , Oki Eiji , Miura Daisuke , Tsurimoto Toshiki , Maehara Yoshihiko , Kitao Hiroyuki
Published: May 2020

DNA replication stress (DRS) is a predominant cause of genome instability, a driver of tumorigenesis and malignant progression. Nucleoside analogue-type chemotherapeutic drugs introduce DNA damage and exacerbate DRS in tumor cells. However, the mechanisms underlying the antitumor effect of these drugs are not fully understood. Here, we show that the fluorinated thymidine analogue trifluridine (FTD), an active component of the chemotherapeutic drug trifluridine/tipiracil, delayed DNA synthesis by human replicative DNA polymerases by acting both as an inefficient deoxyribonucleotide triphosphate source (FTD triphosphate) and as an obstacle base (trifluorothymine) in the template DNA strand, which caused DRS. In cells, FTD decreased the thymidine triphosphate level in the dNTP pool and increased the FTD triphosphate level, resulting in the activation of DRS-induced cellular responses during S-phase. In addition, replication protein A–coated single-stranded DNA associated with FancD2 and accumulated after tumor cells completed S-phase. Finally, FTD activated the p53–p21 pathway and suppressed tumor cell growth by inducing cellular senescence via mitosis skipping. In contrast, tumor cells that lost wild-type p53 underwent apoptotic cell death via aberrant late mitosis with severely impaired separation of sister chromatids. These results demonstrate that DRS induced by a nucleoside analogue–type chemotherapeutic drug suppresses tumor growth irrespective of p53 status by directing tumor cell fate toward cellular senescence or apoptotic cell death according to p53 status.

Implications:

Chemotherapeutic drugs that increase DRS during S-phase but allow tumor cells to complete S-phase may have significant antitumor activity even when functional p53 is lost.
Recurrent Guillain-Barré and Fisher Syndromes in Two Patients Who Were Subsequently Diagnosed with Aplastic Anemia
Authors: Tomohara Saori , Harano Risa , Wada Shinichi , Ohashi Ikkei , Yoshino Fumitaka , Mito Daiki , Kadowaki Masanori , Takase Ken , Kuwashiro Takahiro , Takaba Hitonori , Yasaka Masahiro , Okada Yasushi
Published: May 2020

Guillain-Barré (GBS) and Fisher (FS) syndromes rarely recur and the characteristics of recurrence have not been fully elucidated. We describe the cases of 2 patients with GBS or FS that recurred more than twice and who were subsequently diagnosed with aplastic anemia. Case 1 was a 66-year-old man who was diagnosed with aplastic anemia 10 months before admission with limb ataxia and a sensory disturbance of the distal limbs that developed 3 days after an upper respiratory tract infection. He had a history of double vision with ataxia at the ages of 38 and 56 years. Case 2 was a 66-year-old woman who had been treated for aplastic anemia 1 year previously. She had a history of upper limb weakness after upper respiratory tract infections at the ages of 39 and 60 years. Tendon reflexes were absent in both patients at the time of onset and they were respectively diagnosed with FS and GBS and treated with intravenous immunoglobulin. No neurological deficits persisted. Blood findings showed that both were positive for IgG type ganglioside antibodies and HLA-DR15. The positive HLA-DR15 might have been associated with the recurrent GBS or FS and the development of aplastic anemia.
The metaphysical “monistic” approach of the Platonic Timaeus by the Neo-Platonist Proclus
Authors: Terezis Christos , Petridou Lydia
Published: May 2020

In this article, we focus on Proclus' commentary on Plato's Timaeus (30a3-6) about how the divine Demiurge intervenes in matter. It is an interesting extract due to the fact that Proclus manages to combine philosophical perspective with theological interpretation and scientific analysis. In the six chapters of the article, we present the theory on dualism established by the representatives of Middle Platonism, we approach the question of the production of the corporeal hypostases, we examine limit and unlimited as productive powers, we explain production in the sense of co-production as well as why matter without qualities is excluded from the entire procedure, and we discuss the principle of the supremacy of the supreme Principle. The most important conclusion drawn according to Proclus, who adopts moderate skepticism, is that, although in his early dialogues Plato tends to dualism, he does this for methodological purposes, for Plato's views are actually connected with ontological monism.