Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Activation of Mutant p53 by Platinum Analogues in Cisplatin-Resistant Cells Is Dependent on Phosphorylation

Dysfunctionality of the p53 tumor suppressor is a major cause of therapeutic drug resistance in cancer. Recently, we reported that mutant, but otherwise functional, p53v172F was inactivated in cisplatin-resistant 2780CP/Cl-16 and 2780CP/Cl-24 human ovarian tumor cells by increased recruitment of the inhibitor MDM4. The current study demonstrates that, unlike cisplatin, platinum analogues oxaliplatin and DACH-diacetato-dichloro-Pt(IV) (DAP) strongly stabilize and activate p53v172F in resistant cells, as indicated by prolonged p53 half-life and transactivation of targets p21 (CDKN1A) and MDM2. This increase in MDM2 reduced MDM4 levels in cell lysates as well as the p53 immunocomplex and prevented reversion of p53 to the inactive p53-MDM2-MDM4–bound state. Phosphorylation of p53 at Ser15 was demonstrated by all three drugs in sensitive A2780 and corresponding resistant 2780CP/Cl-16 and 2780CP/Cl-24 cell lines. However, cisplatin induced Ser20 phosphorylation in A2780 cells only, but not in resistant cells; in contrast, both DAP and oxaliplatin induced this phosphorylation in all three cell lines. The inference that Ser20 phosphorylation is more important for p53 activation was confirmed by ectopic expression of a phosphomimetic (S20D) mutant p53 that displayed reduced binding, relative to wild-type p53, to both MDM2 and MDM4 in p53-knockout A2780 cells. In consonance, temporal studies demonstrated drug-induced Ser15 phosphorylation coincided with p53 stabilization, whereas Ser20 phosphorylation coincided with p53 transactivation. Implications: Cisplatin fails to activate the pathway involved in phosphorylating mutant p53v172F at Ser20 in resistant cells, but this phosphorylation is restored by oxaliplatin and DAP that reactivates p53 function and circumvents cisplatin resistance. Mol Cancer Res; 15(3); 328–39. ©2016 AACR.
Making "Fast" Atomic Operations Computationally Tractable

Communication overhead is the most commonly used performance metric for the operation com- plexity of distributed algorithms in message-passing environments. However, aside with com- munication, many distributed operations utilize complex computations to reach their desired outcomes. Therefore, a most accurate operation latency measure should account of both compu- tation and communication metrics. In this paper we focus on the efficiency of read and write operations in an atomic read/write shared memory emulation in the message-passing environment. We examine the operation com- plexity of the best known atomic register algorithm, presented in [2], that allows all read and write operations to complete in a single communication round-trip. Such operations are called fast. At its heart, the algorithm utilizes a predicate to allow processes to compute their outcome. We show that the predicate used in [2] is computationally hard, by devising a computationally equivalent problem and reducing that to Maximum Biclique, a known NP-hard problem. To improve the computational complexity of the algorithm we derive a new predicate that leads to a new algorithm, we call ccFast, and has the following properties: (i) can be computed in polyno- mial time, rendering each read operation in ccFast tractable compared to the read operations in the original algorithm, (ii) the messages used in ccFast are reduced in size, compared to the original algorithm, by almost a linear factor, (iii) allows all operations in ccFast to be fast, and (iv) allows ccFast to preserve atomicity. A linear time algorithm for the computation of the new predicate is presented along with an analysis of the message complexity of the new algorithm. We believe that the new algorithm redefines the term fast capturing both the communication and the computation metrics of each operation.
Long-Term Health Outcomes in High-Altitude Pulmonary Hypertension.

Robinson, Jeffrey C. , Cheryl Abbott, Christina A. Meadows, Robert C. Roach, Benjamin Honigman, and Todd M. Bull. Long-term health outcomes in high-altitude pulmonary hypertension. High Alt Med Biol. 18:61-66, 2017. BACKGROUND High-altitude pulmonary hypertension (HAPH) is one of several known comorbidities that effect populations living at high altitude, but there have been no studies looking at long-term health consequences of HAPH. We aimed to determine whether HAPH during adolescence predisposes to significant pulmonary hypertension (PH) later in life, as well as identify how altitude exposure and HAPH correlate with functional class and medical comorbidities. METHODS We utilized a previously published cohort of 28 adolescents from Leadville, Colorado, that underwent right heart catheterization at 10,150 ft (3094 m) in 1962, with many demonstrating PH as defined by resting mean pulmonary arterial pressure ≥25 mmHg. We located participants of the original study and had living subjects complete demographic and health surveys to assess for the presence of PH and other medical comorbidities, along with current functional status. RESULTS Seventy-five percent of the individuals who participated in the original study were located. Those with HAPH in the past were more prone to have exertional limitation corresponding to WHO functional class >1. Fifty-five years following the original study, we found no significant differences in prevalence of medical comorbidities, including PH, among those with and without HAPH in their youth. CONCLUSIONS Surveyed individuals did not report significant PH, but those with HAPH in their youth were more likely to report functional limitation. With a significant worldwide population living at moderate and high altitudes, further study of long-term health consequences is warranted.
Chikungunya virus: epidemiology, replication, disease mechanisms, and prospective intervention strategies

Chikungunya virus (CHIKV), a reemerging arbovirus, causes a crippling musculoskeletal inflammatory disease in humans characterized by fever, polyarthralgia, myalgia, rash, and headache. CHIKV is transmitted by Aedes species of mosquitoes and is capable of an epidemic, urban transmission cycle with high rates of infection. Since 2004, CHIKV has spread to new areas, causing disease on a global scale, and the potential for CHIKV epidemics remains high. Although CHIKV has caused millions of cases of disease and significant economic burden in affected areas, no licensed vaccines or antiviral therapies are available. In this Review, we describe CHIKV epidemiology, replication cycle, pathogenesis and host immune responses, and prospects for effective vaccines and highlight important questions for future research.
Atomic Scale Investigation of Orthopyroxene and Olivine Grain Boundaries by Atom Probe Tomography

Olivine (Mg1.8Fe0.2)SiO4 and orthopyroxene (Mg 0.9Fe0.1)SiO3 are the most abundant minerals in Earth’s upper mantle and represent important geochemical reservoirs in Earth. In addition, the rheological properties of these two minerals exert first order control on mantle convection and the dynamics of Earth’s tectonic plates [1, 2]. Both olivine and orthopyroxene have nominal compositions that include Mg, Fe, Si, and O. However due to extensive solubility of non-stoichiometric elements, both minerals may contain a number of impurities, including Ca, Al, Mn, Cr. During deformation, dynamic recrystallization generates new grain-boundaries, which then migrate due to differences in dislocation strain energy between adjacent grains. It has been shown that this grain boundary migration will cause impurities to become segregated along new grain boundaries. Thus, grain boundaries may represent important additional geochemical reservoirs in Earth.
Egg quality in furnished cages for laying hens--effects of crack reduction measures and hybrid.

Egg quality, egg production, and hen use of facilities, with respect mainly to proportion of eggs laid in nests and bird locations after lights-out, were studied in furnished-cage models for six or eight birds. In these cages, most of the eggs are laid in the 25 cm wide nest, i.e., egg laying is concentrated to a much smaller area compared with conventional cages. The study (20 to 80 wk of age) used 1,296 hens of three genotypes Hy-Line White, Hy-Line Brown, and Lohmann Selected Leghorn. Conventional four-hen cages were included as a reference. We separately studied the effects on the proportion of eggs cracked by egg saver wires in front of the egg cradle, long nest curtains, and position of nest opening (rear or front) with 30 or 100% of the nest bottom being lined with AstroTurf. Egg saver wires and long nest curtains lowered the proportions of cracked eggs significantly by softly catching and reducing the speed of the eggs before entering the egg cradle. The position of the nest opening affected none of the measured parameters. Less lining in the bottom of the nest, i.e., a reduction to 30% coverage, resulted in significantly higher proportions of dirty eggs and lower proportions of eggs laid in nests. Hybrid differences were found in most of the measured traits. We concluded that devices like egg savers and long nest curtains are effective measures in reducing cracks in furnished cages, where egg laying is concentrated to a much smaller area than in conventional cages. Reduction of the bottom lining to 30% makes nests less attractive to birds laying eggs.
Selection of tree roosts by male Indiana bats during the autumn swarm in the Ozark Highlands, USA

We identified 162 roosts for 36 male Indiana bats (Myotis sodalis) across 3 study areas in the Ozarks of northern Arkansas, USA, during the autumn swarm (late Aug to late Oct, 2005 and 2006). Bats utilized 14 tree species; snags of shortleaf pine (Pinus echinata) were the most utilized (30% of roosts) and pines were selected over hardwoods. Diameter of trees and snags used for roosting ranged from 7.8 cm to 68.6 cm diameter at breast height (dbh), but bats used trees ≥20 cm dbh at a greater proportion than their availability. Roosts were located in a number of different forested cover classes, including shelterwood and group selection stands that had undergone partial harvesting. Roosts in 2 of 3 study areas showed no differences in proportional use of forest cover classes versus availability of those classes. However, in one study area, mature forests (≥50 yr old) that had been burned once recently and stands burned multiple times over the past 10 years were used at a greater proportion than their availability, whereas mature forests that were not burned were used at a lower proportion than their availability. An examination of stand age data indicated that 98% of all roosts were located in stands ≥38 years old, suggesting that this is an important age threshold for roost selection in the Ozark Mountains. Bats in 2 study areas roosted at lower slopes in the higher elevation portions of the study areas, whereas no selection for topographic aspect were observed in all 3 study areas. Our data indicate that perceived habitat selection by a species may differ within the same geographic region and these differences could be due to factors such as differing selection among individuals, differences in juxtaposition of landscape components and cover types, and differing biological components such as the distribution of predators and predator densities. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Preschool Multiple‐Breath Washout Testing. An Official American Thoracic Society Technical Statement

Background: Obstructive airway disease is nonuniformly distributed throughout the bronchial tree, although the extent to which this occurs can vary among conditions. The multiple‐breath washout (MBW) test offers important insights into pediatric lung disease, not available through spirometry or resistance measurements. The European Respiratory Society/American Thoracic Society inert gas washout consensus statement led to the emergence of validated commercial equipment for the age group 6 years and above; specific recommendations for preschool children were beyond the scope of the document. Subsequently, the focus has shifted to MBW applications within preschool subjects (aged 2‐6 yr), where a “window of opportunity” exists for early diagnosis of obstructive lung disease and intervention. Methods: This preschool‐specific technical standards document was developed by an international group of experts, with expertise in both custom‐built and commercial MBW equipment. A comprehensive review of published evidence was performed. Results: Recommendations were devised across areas that place specific age‐related demands on MBW systems. Citing evidence where available in the literature, recommendations are made regarding procedures that should be used to achieve robust MBW results in the preschool age range. The present work also highlights the important unanswered questions that need to be addressed in future work. Conclusions: Consensus recommendations are outlined to direct interested groups of manufacturers, researchers, and clinicians in preschool device design, test performance, and data analysis for the MBW technique.
CES-533: Analysis of the Event-related Potentials induced by cuts in feature movies and evaluation of the possibility of using such ERPs for understanding the effects of cuts on viewers

In this paper, we analyse the Event-Related Potentials (ERPs) produced by cuts where the scenes before and after the cut are narratively related. In tests with 6 participants and 930 cuts from 5 Hollywood feature movies we found that cuts produce a large negative ERP with an onset 100 ms after a cut and a duration of 600 ms, distributed over a very large region of the scalp. The real-world nature of the stimuli makes it hard to characterise the effects of cuts on a trial-by-trial basis. However, we found that aggregating data across all electrodes and averaging the ERPs elicited by cuts across all participants (a technique we borrowed from collaborative brain-computer interfaces) produced more reliable information. In particular we were able to reveal a relationship between the length of shots and the amplitude of the corresponding ERP with longer scenes producing bigger amplitudes. We also found that amplitudes vary across and within movies, most likely as a consequence of movie directors and editors using different choices of cutting techniques. In the future, we will explore the possibility of turning these ? findings into a collaborative brain-computer interface for aiding test screening by evaluating whether specific cuts have their intended effect on viewers.
Stochastic Deconvolutional Neural Network Ensemble Training on Generative Pseudo-Adversarial Networks

The training of Generative Adversarial Networks is a difficult task mainly due to the nature of the networks. One such issue is when the generator and discriminator start oscillating, rather than converging to a fixed point. Another case can be when one agent becomes more adept than the other which results in the decrease of the other agent's ability to learn, reducing the learning capacity of the system as a whole. Additionally, there exists the problem of Mode Collapse which involves the generators output collapsing to a single sample or a small set of similar samples. To train GANs a careful selection of the architecture that is used along with a variety of other methods to improve training. Even when applying these methods there is low stability of training in relation to the parameters that are chosen. Stochastic ensembling is suggested as a method for improving the stability while training GANs.
Herpesvirus Respiratory Infections in Immunocompromised Patients: Epidemiology, Management, and Outcomes

Abstract Among immunocompromised individuals, members of the human Herpesviridae family are frequently encountered pathogens. Cytomegalovirus, herpes simplex virus 1 and 2, varicella zoster virus, Epstein–Barr virus, and human herpesvirus-6, -7, and -8 all establish latency after infection and can reactivate during periods of immunosuppression, leading to both direct and indirect adverse effects on the host including severe organ dysfunction as well as allograft rejection and loss after transplantation. While not all herpesviruses are primary respiratory pathogens, many of their manifestations include involvement of the respiratory tract. This article discusses the individual viruses, their epidemiology, and clinical manifestations as well as recommended treatment and preventive strategies.
Don't Talk Unless I Say So! Securing the Internet of Things with Default-Off Networking

The Internet of Things (IoT) is changing the way we interact with everyday objects. "Smart" devices will reduce energy use, keep our homes safe, and improve our health. However, as recent attacks have shown, these devices also create tremendous security vulnerabilities in our computing networks. Securing all of these devices is a daunting task. In this paper, we argue that IoT device communications should be default-off and desired network communications must be explicitly enabled. Unlike traditional networked applications or devices like a web browser or PC, IoT applications and devices serve narrowly defined purposes and do not require access to all services in the network. Our proposal, Bark, a policy language and runtime for specifying and enforcing minimal access permissions in IoT networks, exploits this fact. Bark phrases access control policies in terms of natural questions (who, what, where, when, and how) and transforms them into transparently enforceable rules for IoT application protocols. Bark can express detailed rules such as "Let the lights see the luminosity of the bedroom sensor at any time" and "Let a device at my front door, if I approve it, unlock my smart lock for 30 seconds" in a way that is presentable and explainable to users. We implement Bark for Wi-Fi/IP and Bluetooth Low Energy (BLE) networks and evaluate its efficacy on several example applications and attacks.
Provided for Non-commercial Research and Education Use. Not for Reproduction, Distribution or Commercial Use. Estimates of Critical Acid Loads and Exceedances for Forest Soils across the Conterminous United States

Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit: This simple mass balance equation estimated that 17% of us forest soils exceed their critical acid load by more than 250 eq ha-J yr-l , and these areas are predominantly located in the northeastern US. Abstract Concern regarding the impacts of continued nitrogen and sulfur deposition on ecosystem health has prompted the development of critical acid load assessments for forest soils. A critical acid load is a quantitative estimate of exposure to one or more pollutants at or above which harmful acidification-related effects on sensitive elements of the environment occur. A pollutant load in excess of a critical acid load is termed exceed-ance. This study combined a simple mass balance equation with national-scale databases to estimate critical acid load and exceedance for forest soils at a l_km2 spatial resolution across the conterminous US. This study estimated that about 15% of US forest soils are in exceedance of their critical acid load by more than 250 eq ha-I yr-I , including much of New England and West Virginia. Very few areas of exceedance were predicted in the western US. Published by Elsevier Ltd.
High Sensitivity Ultraviolet Light Off-Stoichiometric Silicon Oxide-Based Sensors

We have developed a UV silicon detector made of silicon and off-stoichiometric silicon dioxide that shows high efficiency and is completely compatible with silicon devices technology. The silicon-based UV detector present a solar cell-like structure which does not require any voltage source. In addition, an off-stoichiometric silicon dioxide film (Silicon Rich Oxide) with silicon nanocrystals has been integrated to this structure. It is shown that the spectral response is due to the high photoluminescence of Si nanocrystals in the visible region when illuminated with UV light and an increase of 100% in the UV detector efficiency is observed with respect to conventional silicon dioxide layers.
A switched‐capacitor skew‐tent map implementation for random number generation

Piecewise linear one‐dimensional maps have been proposed as the basis for low‐power analog and mixed‐signal true random number generators (TRNGs). Recent research has moved towards conceiving maps that operate robustly under the consideration of parameter variations. In this paper, we introduce an oscillator circuit mapping a low‐complexity map known as the skew‐tent. This oscillator is employed as the basis for a TRNG scheme. Simulation results in TSMC 0.18 μm validate the chaotic oscillator and the randomness of the TRNG scheme is verified with the NIST test suite 800‐22. Copyright © 2016 John Wiley & Sons, Ltd.
watermelon crops Running head : native bees buffer climate warming

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/gcb.12264 This article is protected by copyright. All rights reserved. Received Date : 17-Mar-2013 Accepted Date : 19-Apr-2013 Article type : Primary Research Articles
A sound and complete definition of linearizability on weak memory models

Linearizability is the standard correctness notion for concurrent objects, i.e., objects designed to be accessed simultaneously by multiple threads. In this paper, we explain why the original definition of linearizability is not applicable to code running on the weak memory models supported by modern multicore architectures, and provide an alternative definition which is applicable. In contrast to earlier work, our definition is proved to be both sound and complete. Furthermore, while earlier work has focussed on linearizability for the TSO (Total Store Order) architecture, ours is applicable to any existing weak memory model. We illustrate how it can be used to prove the correctness of a simple case study on the widely used TSO, Power and ARM architectures.
Dimmable MR16 LED drivers with low output ripple and wide duty ratio operating range

In this paper, a novel single‐switch DC–DC converter is proposed for dimmable MR16 light‐emitting diode (LED) drivers. The proposed driver can achieve very low output voltage ripple without using MHz switching frequency; therefore, small non‐electrolytic capacitors can be used to achieve longer lifetime and higher efficiency. Also, because of special merit of the proposed converter, it can be designed so that much wider duty ratio operating range can be achieved for LEDs. Hence, better digital dimming level resolution can be attained. Finally, a prototype driver for MR16 LED lamps is constructed to demonstrate the effectiveness of the converter. Experimental results show that a maximum efficiency of 92% can be achieved. Copyright © 2016 John Wiley & Sons, Ltd.