cssi/SciSciGPT-SciSciNet huggingface dataset:
Fighting Internet Piracy: The French Experience With The Hadopi Law

With the ever-increasing speed of the Internet and the ever-increasing power of personal computers and mobile devices, illegal downloading affects not only recorded music, but also movies and other medias. To stem the loss of revenues caused to copyright holders, France passed the Hadopi Law in September 2009 to be enforced by a new agency - the Hadopi Authority.
A REVIEW OF SENSING AND DISTRIBUTED DETECTION ALGORITHMS FOR COGNITIVE RADIO SYSTEMS

Optimized spectrum sensing using distributed detection techniques for secondary user spectrum access is becoming important in Cognitive Radio (CR) systems, which have been proposed to utilize the available frequency spectrum more efficiently. For achieving best performance and ensuring minimal acceptable interference to spectrum owners, it is important to accurately sense and detect the presence or absence of primary licensed users. For this purpose, the solutions learned within the framework of distributed detection in wireless sensor networks have been considered. In this paper, we review sensing algorithms and approaches of distributed detection and their relevance to CR systems.
Robustness, Diversity of Evidence, and Probabilistic Independence

In robustness analysis, hypotheses are supported to the extent that a result proves robust, and a result is robust to the extent that we detect it in diverse ways. But what precise sense of diversity is at work here? In this paper, I show that the formal explications of evidential diversity most often appealed to in work on robustness – which all draw in one way or another on probabilistic independence – fail to shed light on the notion of diversity relevant to robustness analysis. I close by briefly outlining a promising alternative approach inspired by Horwich’s (Probability and evidence. Cambridge University Press, Cambridge, 1982) eliminative account of evidential diversity.
Multiple Endocrine Neoplasia Syndromes

Multiple endocrine neoplasia (MEN) syndromes include several types of autosomal dominant inherited familial cancer syndromes, each characterized by a different pattern of endocrine gland tumors in affected individuals. The two major types are MEN1 (Wermer syndrome) and MEN2 (Sipple syndrome). MEN1 is an autosomal dominant disorder characterized by a high frequency of peptic ulcer disease and primary endocrine abnormalities involving the parathyroids (90–97% of patients), pancreatic islets (30–80% of patients; including adenoma, prolactinoma, insulinoma, glucagonoma, gastrinoma, etc.), and anterior pituitary (15–50% of patients).1 MEN2 includes subtypes MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC, non-MEN), with the primary clinical features of medullary thyroid carcinoma (MTC; 95% of patients), pheochromocytoma (pheo; 50% of MEN2A and MEN2B), parathyroid hyperplasia (15–30% of MEN2A and rarely in MEN2B), plus mucosal neuromas (lips and tongue), ganglioneuromas of the gastrointestinal tract, and marfanoid habitus in MEN2B only.1 The MEN2A diagnostic category characterizes approximately 60% to 90% of patients with MEN2, FMTC accounts for 5% to 35%, and MEN2B for about 5%.2 In addition, MTC and pheo may be bilateral or multifocal with an earlier age of onset than sporadic occurrence of the same tumor type.
Black Venus Hottentot Revisited: Gratuitous Use of Black Women's Bodies and the Role of Race and Gender in Campus and Academic Reactions

This book chapter, entitled Black Venus Hottentot Revisited: Gratuitous Use of Black Women’s Bodies and the Role of Race and Gender in Campus and Academic Reactions (Published in RACE TO INJUSTICE: LESSONS LEARNED FROM THE DUKE UNIVERSITY LACROSSE PLAYERS’ RAPE CASE, Carolina Academic Press, edited by Michael Seigel), analyzes the class/race/gender implications of the campus reactions to the Duke rape allegations as well as explores the potential for added protections for women employed in the erotic labor force. The chapter further focuses on sexual profiling in the erotic labor force and discusses how women of color who are engaged in erotic work are even more burdened by such profiling. In doing so, it explores the perception of women of color’s bodies, historically and currently, as well as the race/class/gender issues raised by the events and narratives surrounding the Duke rape allegations.
Estimating the Weights of Media Tonalities in the Measurement of Media Coverage of Corporations

This study estimates the weights of media tonalities in the measurement of media coverage of corporations by using linear regression analysis. Two new measures—Three Factor Media Favorability (TFMF) index and Four Factor Media Favorability (FFMF) index—are developed based on these estimations. These two measures are compared with other linear function measures of media coverage of corporations. Two types of measures—the measure of media favorability, and the composite measure of media favorability and visibility—are differentiated based on the different roles of media visibility in the formulas. Empirical analyses find that TFMF index and FFMF index have a certain degree of relative advantage over other measures of media favorability in predicting corporate reputation, and a composite measure of media favorability and visibility has a certain degree of relative advantage over the measures of media favorability in predicting corporate reputation. The analyses are based on a content analysis of 2,817 news a...
Canine Staphylococcus pseudintermedius sinonasal infection in human hosts.

Background Staphylococcus pseudintermedius is a gram-positive bacterium commonly found as part of the normal skin and nasal flora of healthy dogs. It may act as an opportunistic pathogen in dogs, but has also been shown to colonize the nasal mucosa of humans. We report 4 cases of chronic rhinosinusitis (CRS) refractory to aggressive medical management with cultures that grew S. pseudintermedius, with clinical improvement only after initiating culture-directed therapy. Methods Retrospective review of 4 patients with CRS treated at a tertiary academic medical center with sinonasal cultures growing S. pseudintermedius. Results All 4 patients are dog owners and had clinical diagnoses of CRS. Three of the 4 patients had a diagnosis related to immune dysfunction (sarcoidosis, Crohn's disease, history of lymphoma). After undergoing endoscopic sinus surgery, each patient was treated with aggressive medical therapy but continued to have purulent nasal discharge. Sinonasal cultures repeatedly grew S. pseudintermedius in all cases, with 3 patients’ dogs also having had concurrent S. pseudintermedius wound infections of the ear and leg with similar antibiotic susceptibilities. Treatment with culture-directed therapy improved the infections in all cases. Conclusion Opportunistic pathogens have a propensity to exacerbate infection in CRS patients with immune dysfunction. We report the first case series of sinonasal S. pseudintermedius infection in humans. Though a rare cause of disease, pathogens such as S. pseudintermedius from nonhuman hosts should be considered in the management of CRS patients refractory to medical therapy.
Psammoma Bodies in Malignant Carcinoid Tumor Metastases

A clinically and histopathologically well-documented case of malignant carcinoid tumor (with carcinoid syndrome) is described. The presence of numerous psammoma bodies in metastatic carcinoid tumor deposits, confirmed by histochemical and ultrastructural analyses, represents a heretofore unreported finding.
ACOUSTIC MEASUREMENTS OF A PULSE DETONATION ENGINE

An experimental investigation on the directivity of acoustic emissions from a pulse detonation engine (PDE) was performed in an anechoic facility using a circular array of eight microphones (62 to 167 deg). The acoustic pressure-time traces for the baseline configuration were observed to be composed of an impulsive shock followed by a fast transient decay to ambient conditions. The spectra were characterized by a fundamental broadband distribution in the low frequency range of less than 1 kHz and a 20dB/decade decay rate at frequencies greater than 10 kHz. The higher frequency content is a result of the impulse source of the PDE blast-wave, while the fundamental mode was attributed to the approximate 1 to 2 ms transient following the blast-wave. The PDE operating conditions were systematically varied during the tests to quantify their effects on the acoustic emissions. The results showed an increase in OASPL with fill-fraction and a logarithmic increase with PDE cycle frequency. Fill-fraction was found to be an appropriate parameter for normalizing PDE acoustic data from different detonation tube lengths. In addition, three modes of operation of the PDE were also identified based on the value of fill-fraction. The sensitivity of the PDE acoustic levels to exhaust nozzle geometry was also studied. A converging nozzle showed global reduction in OASPL at all fill-fractions, while diverging nozzles experienced OASPL reductions in only the downstream angles. The results suggest that the acoustic levels were sensitive to both the nozzle length and area ratio, and it was observed that this sensitivity changed with fillfraction.
Action of Chloromycetin on Salmonella.

SummaryChloromycetin inhibits the growth of Salmonella organisms in vitro remarkably, but is not able even in large amounts to control Salmonella infections in mice. Neither the oral nor the subcutaneous form of treatment prevented the fatal outcome of the disease in most animals, although it prolonged the survival time. Its action in the animals was bacteriostatic and not bactericidal. Due to its absorption conditions, Chloromycetin exerts no influence on the intestinal flora, when given orally.
An Analysis of a Completed Temper Bead Weld Repair Performed on an Amine Tower

An amine tower was inspected and was shown to have wall loss over the majority of the circumference. A repair plan was developed which included welding onto the tower while the tower remained in operation. The two step repair plan first required welding two Inconel 625 rings to the SA516-70N steel tower and then welding a stainless steel sleeve to the Inconel 625 rings encapsulating the corroded area. Since the repair welds could be exposed to an amine environment if the steel tower corroded through, API Recommended Practice 945 (API RP 945) was used to aid in the qualification of the welding procedure. API RP 945 recommends a post-weld heat treatment (PWHT) to reduce hardness and relieve stress, but since the planned repair was to be made in-service, PWHT was not preferred. To address the hardness aspect a temper bead technique was used to successfully qualify a welding procedure, without PWHT, in accordance with 2006 NBIC and 2004 ASME Boiler and Pressure Vessel Code Section IX with hardness values below 200 Brinell. The temper bead welding procedure used Inconel 182 SMAW electrodes and required strict welding heat input control and weld bead placement. The heat input could be monitored by controlling the welding parameters or by using the run-out ratio diagram. The temper bead passes needed to be deposited in such a manner that the weld toe of the temper bead was no more than 3/32 in. (2.4 mm) away from the weld toe of the initial layer. To address the residual stress aspect the procedure qualification weld was thermo-mechanically modeled to predict the residual stress distribution on the inside surface of the amine tower. The repair procedure was performed on the operating vessel to emplace the straps and the sleeve. Shortly afterwards, the tower wall was breached and the internal environment reached the annulus inside the sleeve. Operation continued for several months until the replacement vessel was available. Once the vessel was removed from service, a section of the repaired area was examined for residual stresses and hardness in the carbon steel. The peak residual stresses were lower than predicted by the analysis from the qualification stage. However, the measured heat affected zone (HAZ) hardness was well above the desired level of 200 Brinnell. Analysis showed that the increased hardness level correlated with improper temper bead placement [i.e., temper bead to weld toe spacing greater than 3/32 in. (2.4 mm)] along with other indications of deviations from the qualified procedure.Copyright © 2010 by ASME
Triggering of ST-elevation myocardial infarction by ambient wood smoke and other particulate and gaseous pollutants

We previously observed increased odds of ST-elevation myocardial infarctions (STEMIs) associated with increased ambient fine particulate matter (PM2.5) in the previous hour. However, data are lacking on the effects of specific PM sources. Using data from 362 patients, a case-crossover design, and conditional logistic regression, we estimated the relative odds of STEMI associated with increased Delta-C (wood smoke), black carbon (BC; traffic), PM2.5, and gaseous pollutants in the previous 1-72 h. We did not observe increased odds of STEMIs associated with increased Delta-C or BC. We did observe increased odds associated with each 7.1 μg/m3 increase in PM2.5 (OR (95% CI): 1.17 (0.99, 1.39)) and each 19.9 p.p.b. increase in ozone (O3; 1.27 (1.00, 1.63)) in the previous hour, and each 0.22 p.p.m. increase in 48-h carbon monoxide (CO) concentrations (1.32 (1.00, 1.73]). Larger relative odds were associated with PM2.5 in May-October, and O3 and CO in November-April. Increased PM2.5, O3, and CO, but not wood smoke or BC, were associated with increased odds of STEMI, and effects may differ by season. Studies using spatially adjusted pollution estimates are needed, as well as studies further examining O3 and CO effects on the risk of STEMI.
Abstract 201: Are Patients With Atrial Fibrillation Willing to Consider New Strategies to Prevent Stroke? A Qualitative Analysis of Community-Based Focus Groups

Introduction: Atrial fibrillation (AF) is a common arrhythmia affecting nearly five million Americans and is the cause of one in six strokes. The FDA has approved new therapies to prevent stroke in patients with AF, including several medications and a procedural device, all shown to be equivalent to, or better than, warfarin. In light of these new options there is a renewed focus in the literature on the evaluation of thromboembolism versus bleeding risk. Determining optimal stroke prevention therapy is a preference-sensitive decision appropriate for shared decision making (SDM). However, values and preferences of patients with AF in this new context are unknown. Methods: To identify patient values and preferences around the choice of strategy for stroke prevention in AF, focus groups were conducted. Demographic data were collected and a semi-structured interview guide was used. Transcripts of the audio-recorded focus groups were qualitatively evaluated and characterized into themes. Results: Five focus groups were completed in May of 2015: two in senior living facilities, one in a community-based senior resource center, and two in anticoagulation clinics. Of the participants, 60% (25 of 42) were women and the mean age was 82 years. The majority of participants (64%) (27 of 42) had a history of AF and 93% (39 of 42) took aspirin or another blood thinner. There was limited experience with major bleeding. Qualitative analysis revealed three main themes: 1) Participants described a fear of debilitating stroke, with varying willingness to accept inconveniences associated with blood thinners; 2) Some participants were reluctant to change long-term anticoagulation regimens and others were interested in exploring new strategies; and 3) In order to consider alternate therapies for stroke prevention, participants emphasized the importance of mutual respect and trust with their physicians. Conclusion: Focus group participants expressed a fear of debilitating stroke, with varying levels of acceptance of inconveniences and potential bleeding associated with blood thinners. Among a subset of participants, there was willingness to consider new stroke prevention therapies; however, this was preferred with a known, trusted physician. Subspecialized clinicians offering new therapies may be challenged to establish perceived mutual respect with patients, traditionally built over time, and this may be required for patients to consider new therapies. Future research is needed to determine best practices for both establishing mutual respect within a referral practice and incorporating patient values and preferences into stroke prevention decision making in the context of atrial fibrillation.
Slow slip events and time‐dependent variations in locking beneath Lower Cook Inlet of the Alaska‐Aleutian subduction zone

We identify a series of abrupt changes in GPS site velocities in Lower Cook Inlet, Alaska, in late 2004, early 2010, and late 2011. The site motions during each time period are nearly linear. The surface deformations inferred from GPS for pre-2004 and 2010–2011 are similar to each other, as are 2004–2010 and post-2011. We estimate the slip distribution on the Alaska-Aleutian subduction plate interface accounting for upper plate block rotations and interpret this toggling between two deformation patterns as caused by transient slip. We find that by allowing negative slip deficit rates (i.e., creep rates in excess of relative plate motion), the data in Lower Cook Inlet are fit significantly better during pre-2004 and 2010–2011, suggesting the occurrence of slow slip events (SSEs) there during those time periods. The earlier SSE lasted at least 9 years (observations in that area began in 1995) with Mw ~7.8. The latter SSE had almost the same area as the earlier one and a duration of ~2 years with Mw ~7.2. During 2004–2010 and post-2011, the inversions result in only positive slip deficit rates (i.e., locking) in Lower Cook Inlet. Slip rates are nearly constant during the Lower Cook Inlet SSEs, and the events start and stop abruptly. Both of these properties contrast with observations of SSEs in Upper Cook Inlet and elsewhere. The Lower Cook Inlet SSEs are consistent with previously proposed duration-magnitude scaling laws and demonstrate that slow slip events can last as long as a decade.
Evaluation and Validation of Measurement Uncertainty of Megohm Meter CalibrationDevice Error Value

The measurement uncertainty of megohm meter calibration device error value has been analyzed and evaluated in detail according to the evaluation methods and steps of measurement uncertainty. The credibility of calibration results and the rationality of the uncertainty evaluation have been verified through the comparison test from China Institute of Metrology. The proposed method in this paper will provide a lot ofy references for the uncertainty evaluation of the same device type.
Do Forest Commons Contribute to International Environmental Initiatives? A Socio-Ecological Analysis of Nepalese Forest Commons in view of REDD+

i Dedication iii Acknowledgements iv List of Tables xi List of Figures xii List of Abbreviations xiii Chapter 1: Introduction and Background 1 1.
Camera calibration: a personal retrospective

Computer vision is a key branch of artificial intelligence, aiming at understanding the surrounding environment from the visual information captured by cameras. 3D computer vision is a subfield of computer vision that focuses on extracting 3D metric information from 2D images. This is a very challenging task since what we have in an image is the projection of a 3D scene, whose depth information is lost during image formation (image projection).
The R/evolution of civic engagement: an exploratory network analysis of the Facebook groups of occupy Chicago

ABSTRACTThis study explores the role of social media as mediating structures for civic engagement. A network analysis of 2829 Facebook groups joined by 600 randomly sampled occupy Chicago (OC) participants shows that OC is embedded in diverse interconnected voluntary groups mediated by social media. The observed patterns of interconnection reveal a loosely connected, fragmented, and clustered structure. Such a structure may enable publics, as self-organized social groups shaped in networked flows of communication, to shift in and out of more established institutional structures and formal civic organizations to form ‘flexible network-domains’ at developing moments of mobilization. The study explains the empirical patterns of civic affiliation in the context of the broad historical structural changes and the specific characteristics of contemporary forms of mediated sociality.
Late recanalization of basilar artery occlusion in a previously healthy 17-month-old child.

Endovascular treatment of acute ischemic stroke in children is increasingly being reported, although the time window for intervention is unclear. We describe a previously healthy 17-month-old child who presented with vertebral artery thrombosis and cerebellar stroke requiring posterior fossa decompression. She later progressed to basilar artery thrombosis treated with mechanical thrombectomy 50 hours after clinical decline. At 3 month follow-up, the patient had a modified Rankin Scale score of 0.
Running reduces firing but improves coding in rodent higher-order visual cortex

Running profoundly alters stimulus-response properties in mouse primary visual cortex (V1), but its effects in higher-order visual cortex remain unknown. Here we systematically investigated how locomotion modulates visual responses across six visual areas and three cortical layers using a massive dataset from the Allen Brain Institute. Although running has been shown to increase firing in V1, we found that it suppressed firing in higher-order visual areas. Despite this reduction in gain, visual responses during running could be decoded more accurately than visual responses during stationary periods. We show that this effect was not attributable to changes in noise correlations, and propose that it instead arises from increased reliability of single neuron responses during running.
Lamp1 Increases the Efficiency of Lassa Virus Infection by Promoting Fusion in Less Acidic Endosomal Compartments

ABSTRACT Lassa virus (LASV) is an arenavirus whose entry into host cells is mediated by a glycoprotein complex (GPC) comprised of a receptor binding subunit, GP1, a fusogenic transmembrane subunit, GP2, and a stable signal peptide. After receptor-mediated internalization, arenaviruses converge in the endocytic pathway, where they are thought to undergo low-pH-triggered, GPC-mediated fusion with a late endosome membrane. A unique feature of LASV entry is a pH-dependent switch from a primary cell surface receptor (α-dystroglycan) to an endosomal receptor, lysosomal-associated membrane protein (Lamp1). Despite evidence that the interaction between LASV GP1 and Lamp1 is critical, the function of Lamp1 in promoting LASV infection remains poorly characterized. Here we used wild-type (WT) and Lamp1 knockout (KO) cells to show that Lamp1 increases the efficiency of, but is not absolutely required for, LASV entry and infection. We then used cell-cell and pseudovirus-cell surface fusion assays to demonstrate that LASV GPC-mediated fusion occurs at a significantly higher pH when Lamp1 is present compared to when Lamp1 is missing. Correspondingly, we found that LASV entry occurs through less acidic endosomes in WT (Lamp1-positive) versus Lamp1 KO cells. We propose that, by elevating the pH threshold for fusion, Lamp1 allows LASV particles to exit the endocytic pathway before they encounter an increasingly acidic and harsh proteolytic environment, which could inactivate a significant percentage of incoming viruses. In this manner Lamp1 increases the overall efficiency of LASV entry and infection. IMPORTANCE Lassa virus is the most clinically important member of the Arenaviridae, a family that includes six additional biosafety level 4 (BSL4) hemorrhagic fever viruses. The lack of specific antiviral therapies for Lassa fever drives an urgent need to identify druggable targets, and interventions that block infection at the entry stage are particularly attractive. Lassa virus is only the second virus known to employ an intracellular receptor, the first being Ebola virus. Here we show that interaction with its intracellular receptor, Lamp1, enhances and upwardly shifts the pH dependence of fusion and consistently permits Lassa virus entry into cells through less acidic endosomes. We propose that in this manner, Lamp1 increases the overall efficiency of Lassa virus infection.
Emotion Expressions and Personality Integration in Infancy

In this chapter, Dr. Buechler and I suggest some new ways of thinking about emotions in infancy. The concept of emotional development is considered too broad to treat as a single topic. The chapter discusses four developmental processes relating to the emotions and to infant development and infant well- being. The expressions of the emotions in infancy are seen as critical in personality integration and the development of infant-parent and other social relationships. The question of the predictive value of emotion response patterns in infancy is placed in perspective, in part by considering the value of studying emotions in infancy apart from the issue of continuity of infant emotion traits.
Analysis of continuous-contact helical gear pumps through numerical modeling and experimental validation

Abstract External gear pumps are one of the most commonly used types of positive displacement machines in high pressure hydraulic control systems, fuel-injection and fuel transport systems. Despite many merits of the traditional external gear pump design with involute teeth, the significant flow non-uniformity intrinsic of such design is considered to be a detrimental aspect, since it causes undesired noise emissions and mechanical vibrations. A disruptive concept of continuous-contact helical gear pumps (CCHGP) was proposed and successfully commercialized in the recent past. Such concept was proven to have clear advantages in terms of noise emissions. However, a clear interpretation of the displacing action and the transient features of the delivery flow was never addressed in past literature. This paper addresses this gap by first discussing the family of gear profiles suitable for implementing the CCHGP design. Subsequently, an analysis on the kinematic flow ripple is given, showing how such design concept can reduce or even eliminate the kinematic flow pulsations. The paper also presents a numerical approach for modelling the operation of CCHGPs, starting from the modeling of the geometric features necessary for a fluid dynamic analysis based on a lumped parameter approach. For model validation purposes, a commercial CCHGP was tested at the authors’ research center, and the simulation results were compared against the experiments, to show the level of accuracy of the model, as well as it potentials for future design studies.
Enabling Trust and Security: TIPPSS for IoT

The Internet of Things (IoT) has gone from hype to abject reality, and its ubiquity is growing. Ensuring TIPPSS for IoT (Trust, Identity, Privacy, Protection, Safety, and Security) is critical to protect people, devices, infrastructure, and cities in our hyper-connected world.
Maximum Likelihood: Basic Results

As we have seen once we have an estimator and its sampling distribution we can easily obtain confidence intervals and tests regarding the parameter. We now develop the theory of estimation focusing on the method of maximum likelihood, which for parametric models is the most widely used method. This will also supply us with a collection of statistical methods for important problems.
Stock Return and Inflation: An Analysis Based on the State-Space Framework

We briefly discuss the literature investigating the correlation between the stock return and inflation rate. In theory if the equity is a perfect hedge against the inflation the real stock return should bear no correlation with the inflation rate. However, a large literature found that the two appear to be significantly negatively correlated. In principle, the zero correlation implied by the theory must only hold ex-ante. In order to shed further light on this issue we develop a state-space model that allows us to decompose the realized values of the two variables into their expected shocks and the news shocks. We find that the expected returns and expected inflation rate are negatively correlated but with marginal significance.
The Computer: Guidance in Diagnosis and Therapy

The simplistic idea of a computer “making a diagnosis” has been replaced by the recognition that modern decision-support systems entail several related tasks: gathering data, identifying disease categories, assessing individual patient prognosis, suggesting further evaluations, and perhaps educating the physician.1–3 Decision support is no longer an unexplored topic; innumerable articles have been published on the subject, and national and international groups on decision-support systems have been established.
Efficient evaluation of poly-electron populations in natural bond orbital analysis

Abstract We show how a simple natural orbital-based modification of Karafiloglou’s poly-electron population analysis (PEPA) [generalizing conventional one-electron natural population analysis (NPA)] allows efficient numerical evaluation of Born probabilities (populations) for an unlimited variety of localized electronic excitation patterns. The computational advantages are illustrated by simple numerical applications to CH3NH2 and benzene in the framework of natural bond orbital (NBO)-based “NPEPA” keyword implementation in the forthcoming NBO 7.0 program.
The military and the state in Egypt: class formation in the post-Arab uprisings

Since the revolution of 2011, the Egyptian military has emerged as agent of capital accumulation, engaging with international financial institutions and global investors, and simultaneously reorgan...
Chaetocin, a promising new anti-myeloma agent with in vitro and in vivo activity linked to oxidative stress

1535 Chaetocin, a thiodioxopiperazine natural product previously unreported to have anti-cancer effects, was found to have potent anti-myeloma activity. In vitro, IL-6-dependent and -independent myeloma cell lines were readily killed at low nanomolar chaetocin concentrations. Studies of dexamethasone-resistant MM1RL cells and doxorubicin-resistant Pgp overexpressing 8226R cells indicated that drug-resistant myeloma cells are largely non-cross resistant to chaetocin. Based on studies employing a series of paired engineered cell lines, the cytotoxicity of chaetocin appears also to be p53-, caspase 3-, caspase 8-, FADD- and DNA mismatch repair-independent, but somewhat BCL-2 dependent. Ex vivo, chaetocin readily killed sorted and unsorted patient CD138+ myeloma cells, while relatively sparing matched normal CD138- patient marrow leukocytes, normal B-cells and neoplastic B-CLL cells, indicating a high degree of selectivity among even closely lineage-related cells. Furthermore, chaetocin displayed superior ex vivo anti-myeloma activity and selectivity than doxorubicin and dexamethasone. In vivo, in anRRMI 8226 SCID flank xenograft myeloma mouse model, 0.25 mg/kg of chaetocin administered IP showed significant (p Mechanistically, chaetocin is dramatically accumulated in cancer cells (up to 1000-fold over applied concentration) via a process inhibited by glutathione and requiring intact chaetocin disulfides for uptake. Once inside the cell, its anti-cancer activity appears mediated primarily through oxidative stress, as increases in ROS over DMSO control were observed at 200 nM chaetocin treatment (p This research was supported by a Multiple Myeloma Research Foundation Postdoctoral Fellowship (JDT) and by NIH/NCI grants R01 CA97129 and R01 CA98118 (KCB).
Informational Biopolymer Structure in Early Living Forms

The conservative nature of the evolutionary process has preserved in all living species “relics” of the biochemical nature of ancient organisms, including those which lived before the ordinary fossil record was formed. Protein and nucleic acid sequences provide evidence which is particularly amenable to quantitation because certain generally applicable and theoretically understandable principles have characterized their evolution; therefore, it is possible to apply logical and statistical methods to the data to extrapolate into the past. The biochemical evidence in protein and nucleic acid structures can provide information from which to construct a phylogenetic tree encompassing all the main lines of living organisms. Further, it can reveal the nature of ancient molecules in ancestral organisms and of the evolutionary process, and finally it can provide a time scale for measuring the relative antiquity of species divergences and gene duplications. By tracing the course of evolution of the more slowly evolving molecules, we may eventually be able to infer much about the protein and nucleic acid structures in what we have termed the “proto-organism”--the most recent common ancestor of all presently living species, which existed more than 3 billion years ago--and even in the more primitive organisms in the evolutionary line that preceded it. Potentially much information regarding the structure of informational bio-polymers can be elicited; there is sufficient DNA. to code for several thousand different kinds of proteins (of 500 residues) in the bacterium Escherichia coli and for more than a million kinds in a human being. Many re-lated proteins and nucleic acids are found throughout a wide range of organisms--from bacteria to multicellular animals and plants. Chemical structures from five such families of informational molecules in very diverse organisms have now been examined: cytochrome c, ferredoxin, trypsin, transfer ribonucleic acid (RNA), and 5S ribosomal RNA (1). Even from these few, we can draw some interesting inferences about early living organisms.
Automatic Identification of Physical Activity Type and Duration by Wearable Activity Trackers: A Validation Study.

Background: Activity trackers are now ubiquitous in certain populations, with potential applications for health promotion and monitoring and chronic disease management. Understanding the accuracy of this technology is critical to the appropriate and productive use of wearables in health research. Although other peer-reviewed validations have examined other features (eg, steps and heart rate), no published studies to date have addressed the accuracy of automatic activity type detection and duration accuracy in wearable trackers. Objective: The aim of this study was to examine the ability of 4 commercially available wearable activity trackers (Fitbits Flex 2, Fitbit Alta HR, Fitbit Charge 2, and Garmin Vivosmart HR), in a controlled setting, to correctly and automatically identify the type and duration of the physical activity being performed. Methods: A total of 8 activity types, including walking and running (on both a treadmill and outdoors), a run embedded in walking bouts, elliptical use, outdoor biking, and pool lap swimming, were tested by 28 to 34 healthy adult participants (69 total participants who participated in some to all activity types). Actual activity type and duration were recorded by study personnel and compared with tracker data using descriptive statistics and mean absolute percent error (MAPE). Results: The proportion of trials in which the activity type was correctly identified was 93% to 97% (depending on the tracker) for treadmill walking, 93% to 100% for treadmill running, 36% to 62% for treadmill running when preceded and followed by a walk, 97% to 100% for outdoor walking, 100% for outdoor running, 3% to 97% for using an elliptical, 44% to 97% for biking, and 87.5% for swimming. When activities were correctly identified, the MAPE of the detected duration versus the actual activity duration was between 7% and 7.9% for treadmill walking, 8.7% and 144.8% for treadmill running, 23.6% and 28.9% for treadmill running when preceded and followed by a walk, 4.9% and 11.8% for outdoor walking, 5.6% and 9.6% for outdoor running, 9.7% and 13% for using an elliptical, 9.5% and 17.7% for biking, and was 26.9% for swimming. Conclusions: In a controlled setting, wearable activity trackers provide accurate recognition of the type of some common physical activities, especially outdoor walking and running and walking on a treadmill. The accuracy of measurement of activity duration varied considerably by activity type and tracker model and was poor for complex sets of activity, such as a run embedded within 2 walking segments.
Adaptive-Halting Policy Network for Early Classification

Early classification of time series is the prediction of the class label of a time series before it is observed in its entirety. In time-sensitive domains where information is collected over time it is worth sacrificing some classification accuracy in favor of earlier predictions, ideally early enough for actions to be taken. However, since accuracy and earliness are contradictory objectives, a solution must address this challenge to discover task-dependent trade-offs. We design an early classification model, called EARLIEST, which tackles this multi-objective optimization problem, jointly learning (1) to classify time series and (2) at which timestep to halt and generate this prediction. By learning the objectives together, we achieve a user-controlled balance between these contradictory goals while capturing their natural relationship. Our model consists of the novel pairing of a recurrent discriminator network with a stochastic policy network, with the latter learning a halting-policy as a reinforcement learning task. The learned policy interprets representations generated by the recurrent model and controls its dynamics, sequentially deciding whether or not to request observations from future timesteps. For a rich variety of datasets (four synthetic and three real-world), we demonstrate that EARLIEST consistently out-performs state-of-the-art alternatives in accuracy and earliness while discovering signal locations without supervision.
Divergent Effects of Dnmt3a and Tet2 Mutations on Hematopoietic Progenitor Cell Fitness.

Summary The DNA methylation regulators DNMT3A and TET2 are recurrently mutated in hematological disorders. Despite possessing antagonistic biochemical activities, loss-of-function murine models show overlapping phenotypes in terms of increased hematopoietic stem cell (HSC) fitness. Here, we directly compared the effects of these mutations on hematopoietic progenitor function and disease initiation. In contrast to Dnmt3a-null HSCs, which possess limitless self-renewal in vivo, Tet2-null HSCs unexpectedly exhaust at the same rate as control HSCs in serial transplantation assays despite an initial increase in self-renewal. Moreover, loss of Tet2 more acutely sensitizes hematopoietic cells to the addition of a common co-operating mutation (Flt3ITD) than loss of Dnmt3a, which is associated with a more rapid expansion of committed progenitor cells. The effect of Tet2 mutation manifests more profound myeloid lineage skewing in committed hematopoietic progenitor cells rather than long-term HSCs. Molecular characterization revealed divergent transcriptomes and chromatin accessibility underlying these functional differences.
Traits of an Independent Communications Regulator: A Search for Indicators with Teaching Module on Ethics and Corruption

This paper draws on newly undertaken surveys of communications regulators around the world and the current theoretical literature to propose a simple framework for evaluating the independence of a communications regulator that is applicable across diverse political and economic systems. While communications regulators, in an ideal world, are “independent,” still they are embedded in relationships with other segments of society. In the main, there are three segments: (1) other state institutions, such as a communications ministry, competition authority, and legislature, (2) the industry they regulate, and (3) consumers who use communications services. This paper proposes that an independent regulator is one that seeks to enable and promote the interests of consumers and retains some autonomy from pressures of highly concentrated interests of industry and other state institutions. The surveys identify an array of institutional arrangements and procedural tools that communications regulators use to enable the interests of consumer and protect themselves from undue pressure from other groups.
Allergic bronchopulmonary aspergillosis misdiagnosed as recurrent pneumonia

Allergic bronchopulmonary aspergillosis (ABPA) is a disease of the lungs resulting from a hypersensitivity reaction to Aspergillus fumigatus. The disease remains underdiagnosed and as many as 57% of patients are misdiagnosed as pulmonary tuberculosis, pneumonia, pulmonary abscess in China. Here we report the case of a 13-year-old girl with ABPA who presented with productive cough, wheezing, bronchiectasis and decline in lung function, total IgE was 25,180 KU/L, Aspergillus-specific IgE was 34.7 kUA/L. Chest high-resolution computed tomography (CT) showed infiltration, central bronchiectasis, and high-attenuation mucus in the left lower lobe and lingula. On bronchoscopy, a large amount of purulent material and brownish sputum plugs were seen. This case has been diagnosed as pneumonia 3 times before the ABPA diagnosis. For the treatment, corticosteroid (prednisone 0.5 mg/kg/day) plus itraconazole (200 mg, twice a day) were initiated. The girl responded well to the therapy. Two weeks later, she was free of symptoms. Lung function nearly improved to normal. One month later, peripheral eosinophil percentage and IgE decreased to 0.7% and 1,3451 KU/L (46% reduction), respectively. However, the trend of A. fumigatus-specific IgE persistently increased during treatment (from 34.7 KU/L to above 100 KU/L). Chest CT showed improvement in pulmonary infiltration. The present case emphasizes the importance of considering the diagnosis of ABPA in children with uncontrolled pneumonia, hypereosinophilia, and bronchiectasis with a previous history of asthma. Total serum IgE is a useful marker of disease activity and success of therapy while the serum A. fumigatus-specific IgE has limited utility in the follow-up of patients with ABPA.
The Relative Biological Effectiveness of Carbon Ion Radiation Therapy for Early Stage Lung Cancer

Abstract Background and purpose Carbon ion radiation therapy (CIRT) is recognized as an effective alternative treatment modality for early stage lung cancer, but a quantitative understanding of relative biological effectiveness (RBE) compared to photon therapy is lacking. In this work, a mechanistic tumor response model previously validated for lung photon radiotherapy was used to estimate the RBE of CIRT compared to photon radiotherapy, as a function of dose and the fractionation schedule. Materials and Methods Clinical outcome data of 9 patient cohorts (394 patients) treated with CIRT for early stage lung cancer, representing all published data, were included. Fractional dose, number of fractions, treatment schedule, and local control rates were used for model simulations relative to standard photon outcomes. Four parameters were fitted: α, α/β, and the oxygen enhancement ratios of cells either accessing only glucose, not oxygen (OERI), or cells dying from starvation (OERH). The resulting dose–response relationship of CIRT was compared with the previously determined dose–response relationship of photon radiotherapy for lung cancer, and an RBE of CIRT was derived. Results Best-fit CIRT parameters were: α = 1.12 Gy−1 [95%-CI: 0.97–1.26], α/β = 23.9 Gy [95%-CI: 8.9–38.9], and the oxygen induced radioresistance of hypoxic cell populations were characterized by OERI = 1.08 [95%-CI: 1.00–1.41] (cells lacking oxygen but not glucose), and OERH = 1.01 [95%-CI: 1.00–1.44] (cells lacking oxygen and glucose). Depending on dose and fractionation, the derived RBE ranges from 2.1 to 1.5, with decreasing values for larger fractional dose and fewer number of fractions. Conclusion Fitted radiobiological parameters were consistent with known carbon in vitro radiobiology, and the resulting dose–response curve well-fitted the reported data over a wide range of dose-fractionation schemes. The same model, with only a few fitted parameters of clear mechanistic meaning, thus synthesizes both photon radiotherapy and CIRT clinical experience with early stage lung tumors.
Leveraging the Entirety of the Protein Data Bank to Enable Improved Structure Prediction Based on Cross-Link Data.

XLinkDB is a fast-expanding public database now storing more than 100 000 distinct identified cross-linked protein residue pairs acquired by chemical cross-linking with mass spectrometry from samples of 12 species (J. Proteome Res. 2019, 18 (2), 753-758). Mapping identified cross-links to protein structures, when available, provides valuable guidance on protein conformations detected in the cross-linked samples. As more and more structures become available in the Protein Data Bank (Nucleic Acids Res. 2000, 28 (1), 235-242), we sought to leverage their utility for cross-link studies by automatically mapping identified cross-links to structures based on sequence homology of the cross-linked proteins with those within structures. This enables use of structures derived from organisms different from those of samples, including large multiprotein complexes and complexes in alternative states. We demonstrate utility of mapping to orthologous structures, highlighting a cross-link between two subunits of mouse mitochondrial Complex I that was mapped to 15 structures derived from five mammals, its distances there of 16.2 ± 0.4 A indicating strong conservation of the protein interaction. We also show how multimeric structures enable reassessment of cross-links presumed to be intraprotein as potentially homodimeric interprotein in origin.
Effect of prophylactic laser during small-gauge vitrectomy for epiretinal membranes.

Purpose:To determine the rate of post-operative retinal detachment after elective pars plana vitrectomy for epiretinal membrane, and to test for the mitigating effect of prophylactic endolaser.Meth...
Equity-Efficiency Tradeoffs in International Bargaining

This paper analyzes the outcome of international negotiations between asymmetric countries in the absence of efficient transfers. A main result is that there is a equity-efficiency tradeoff to reducing the flexibility of negotiations in making transfers across countries. Specifically, an increase in the inefficiency of transfers will reduce aggregate global welfare but, when the degree of asymmetry is sufficiently small, can result in a more equitable agreement that benefits the country that is at a bargaining disadvantage. Similarly, we demonstrate that increases in bargaining asymmetry can also make the disadvantaged country better-off at the expense of global welfare. As an application, we show that preventing monetary side-payments in trade negotiations between a large and small country can benefit the small country at the expense of the overall efficiency of the agreement.
An Autoregulatory Mechanism Maintains Proper Levels of 22G-siRNA in C. Elegans

RNA interference (RNAi) is an essential regulatory mechanism in all animals. In C. elegans, several classes of small RNAs act to silence or license expression of mRNA targets. ERI-6/7 is required for the production of some endogenous siRNAs and acts as a negative regulator of the exogenous RNAi pathway. We found that the genomic locus encoding eri-6/7 contains two distinct regions that are targeted by endogenous siRNAs. Loss of these siRNAs disrupts eri-6/7 mRNA expression, resulting in increased production of siRNAs from other small RNA pathways because these pathways compete with eri-6/7-dependent transcripts for access to the downstream siRNA amplification machinery. Thus, the pathway acts like a negative feedback loop, to ensure homeostasis of gene expression by small RNA pathways. Similar feedback loops that maintain chromatin homeostasis have been identified in yeast and Drosophila melanogaster, suggesting an evolutionary conservation of autoregulatory mechanisms in gene regulatory pathways.