bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of Targetable Genetic Alterations in Korean Lung Cancer Patients: A Comparison Study of Single-Gene Assays and Targeted Next-Generation Sequencing
Authors: Park Eunhyang , Shim Hyo Sup
Published: November 2019

PurposeEpidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) are ‘must-test’ biomarkers in the molecular diagnostics of advanced-stage lung cancer patients. Although single-gene assays are currently considered the gold standard for these genes, next-generation sequencing (NGS) tests are being introduced to clinical practices. We compared the results of current diagnostics and aimed to suggest timely effective guidance for their clinical use. Materials and MethodsPatients with lung cancer who received both conventional single-gene assays and subsequent targeted NGS testing were enrolled, and the results of their tests were compared. ResultsA total of 241 patients were enrolled, and the EGFR real-time polymerase chain reaction, ALK fluorescence in situ hybridization (FISH), and ROS1 FISH assays exhibited 92.9%, 99.6%, and 99.5% concordance with the NGS tests, respectively. The discordant cases were mostly false-negatives of the single-gene assays, probably due to technical limitation. Of 158 cases previously designated as wild-type, EGFR, ALK, and ROS1 alterations were identified in 10.1%, 1.9%, and 1.3%, respectively, and other targetable alterations were identified in 36.1% of the cases. Of patients with additionally identified actionable alterations, 32.6% (31/95) received matched therapy with a clinical benefit of 48.4% (15/31). ConclusionEven though the conventional and NGS methods were concordant in the majority of cases, NGS testing still revealed a considerable number of additional EGFR, ALK, and ROS1 alterations, as well as other targetable alterations, in Korean advanced-stage lung cancer patients. Given the high frequency of EGFR and other targetable mutations identified in the present study, NGS testing is highly recommended in the diagnosis of Korean lung cancer patients.
Co-rank of weakly parafree 3-manifold groups
Authors: Harvey Shelly , Tweedy Eamonn
Published: November 2019

Recall that a group is called large if it has a finite index subgroup which surjects onto a non-abelian free group. By work of Agol and Cooper-Long-Reid, most 3-manifold groups are large; in particular, the fundamental groups of hyperbolic 3-manifolds are large. In previous work, the first author gave examples of closed, hyperbolic 3-manifolds with arbitrarily large first homology rank but whose fundamental groups do not surject onto a non-abelian free group. We call a group very large if it surjects onto a non-abelian free group. In this paper, we consider the question of whether the fundamental groups of homology handlebodies – which are very close to being free – are very large. We show that the fundamental group of W. Thurston’s tripus manifold, is not very large; it is known to be weakly parafree by Stallings’ Theorem and large by the work of Cooper–Long–Reid since the tripus is a hyperbolic manifold with totally geodesic boundary. It is still unknown if a 3-manifold group that is weakly parafree of rank at least 3 must be very large. However, we more generally consider the co-rank of the fundamental group, also known as the cut number of the manifold. For each integer

g \geq 1

we construct a homology handlebody

Y_g

of genus

g

whose group has co-rank equal to

r(g)

, where

r(g) = g/2

for

g

even and

r(g) = (g+1)/2

for

g

odd. That is, these groups are weakly parafree of rank g and surject onto a free group of rank roughly half of g but no larger.
Динамические свойства нелинейного уравнения вязкоупругости
типа Кирхгофа с граничными условиями акустического управления. I
Authors: Li Fushan , Xi Shuai
Published: November 2019

В данной работе рассматривается нелинейное уравнение вязкоупругости
типа Кирхгофа
$$
u_{tt}-M(\|\nabla u\|^2_2)\Delta u
+\int_0^t h(t-s)\Delta u(s) ds+a|u_t|^{m-2}u_t=|u|^{p-2}u
$$
с начальными условиями и акустическими граничными условиями.
В зависимости от свойств ядер свертки $h$ на бесконечности
будет показано, что энергия решения убывает экспоненциально
или полиномиально при $t\to +\infty$. Наш подход основан на
использовании техники интегральных неравенств и множителей.
Вместо того чтобы применять технику типа Ляпунова к некоторой
возмущенной энергии, мы рассмотрим исходную энергию и покажем,
что она удовлетворяет нелинейному интегральному неравенству,
которое, в свою очередь, дает окончательную оценку убывания.
Библиография: 33 названия.
Об однозначной разрешимости задачи течения
водного раствора полимеров вблизи критической точки
Authors: Petrova Anna Georgievna
Published: November 2019

Рассматривается краевая задача в полуограниченном интервале
для уравнения 4-го порядка с "двойным вырождением":
малый параметр в уравнении стоит
перед произведением искомой функции, обращающейся в нуль на границе,
и ее старшей производной. Такая задача возникает при описании
движения слабых растворов полимеров вблизи критической точки.
При значении параметра, равном нулю, решением является
классическое решение Хименца.
Доказывается однозначная разрешимость задачи
при неотрицательных значениях параметра, не превышающих единицы.
Библиография: 21 название.
Существование и асимптотическая устойчивость
периодических двумерных контрастных структур
в задаче со слабой линейной адвекцией
Authors: Nefedov Nikolai Nikolaevich , Nikulin Egor Igorevich
Published: November 2019

Рассматривается краевая сингулярно возмущенная
периодическая по времени задача для параболического уравнения
реакция-адвекция-диффузия в случае слабой линейной адвекции
в двумерной области. Основной результат данной работы -
обоснование при некоторых достаточных предположениях
существования периодического решения с внутренним переходным слоем
вблизи некоторой замкнутой кривой, а также исследование
асимптотической устойчивости по Ляпунову такого решения.
Для этой цели строится асимптотическое разложение решения;
обоснование существования решения с построенной асимптотикой
проводится с помощью метода дифференциальных неравенств.
Доказательство асимптотической устойчивости по Ляпунову основано
на применении так называемого метода сжимающих барьеров.
Библиография: 20 названий.
Смешанные дробно-дифференциальные уравнения и обобщенные операторно-значные функции Миттаг-Леффлера
Authors: Kolokoltsov Vassili Nikitich
Published: November 2019

Даны максимально общие определения смешанных дробных производных и интегралов с привлечением следующих трех теорий: теории вероятностей, теории операторных полугрупп и теории обобщенных функций. Оказывается, что решения полученных смешанных дробных уравнений с частными производными могут быть выражены через определенный класс полностью монотонных функций, являющихся обобщением обычных функций Миттаг-Леффлера. Библиография: 26 названий.
Surgical outcomes of diabetic hand infections in Lagos, Nigeria
Authors: Mofikoya Bolaji O
Published: November 2019

Background Hand infections in diabetics can be a major cause of functional impairment .In patients with Tropical Diabetic hand syndrome prompt surgical intervention may salvage the hand, but return to premorbid function remain a challenge.Objectives A retrospective study of consecutive diabetic patients with hand infections was done in 2 tertiary institutions in Lagos,Nigeria to identify the epidemiology, modes of presentation, types of surgical intervention and outcomes oftreatment.Results Twenty one patients were studied over a 5 year period. ten males, eleven females .All were type 2 Diabetes. 52.4%(11) were diagnosed less than a year prior to presentation. 61.9%(13) had digit/hand gangrene on presentation. All operated patients (20) had wound debridements. 52.5% (11) digit/hand amputations and this was the commonest surgical procedures done. Other surgeries done include skin grafts and `flap reconstructions. There was a 19% mortality rate. Less than a fifth were able return to their premorbid occupation after 3 months. But all had reduced range of motion in the interphalangeal joints in the adjacent digits.ConclusionsThere is a high morbidity rate for hand infections in the diabetic, even though majority of the hands were salvaged, most patients were unable to return to their premorbid occupation at 3 months.
Secondary organic aerosol formation from photooxidation of furan: effects of NOx and humidity
Authors: Jiang Xiaotong , Tsona Narcisse T. , Jia Long , Liu Shijie , Zhang Hailiang , Xu Yongfu , Du Lin
Published: November 2019

Abstract. Atmospheric furan is a primary and secondary pollutant in
the atmosphere, and its emission contributes to the formation of ultrafine
particles. We investigate the effects of NOx level and humidity on the
formation of secondary organic aerosol (SOA) generated from the
photooxidation of furan in the presence of NaCl seed particles. SOA mass
concentration and yield were determined under different NOx and humidity
levels. A significant difference is observed both in the variation of SOA
mass concentration and SOA yield with the initial experimental conditions.
Varying VOC (volatile organic compound) ∕ NOx ratios over the range 48.1 to 8.2 contributes to the
effective formation of SOA in the presence of NaCl seed particles, with the
SOA mass concentration and SOA yield ranging from 0.96 to
23.46 µg m−3 and from 0.04 % to 1.01 %, respectively. We
found that there was a favourable relationship between the SOA yields and
NOx concentration. In particular, the increase in SOA yield with increasing NOx
concentration was continuously observed at high NOx levels owing to a
corresponding increase in the amount of low-volatility hydroxyl nitrates and
dihydroxyl dinitrates that can partition into the particle phase. In addition,
varying relative humidity (RH) from 5 % to 88 % increased the SOA yield from 1.01 % to
5.03 %. The enhanced SOA formation from humid conditions may result from
the high OH concentration, rapid furan decay rate, enhanced carbonyl-rich
products condensation, and the aqueous-phase reactions. Using hybrid
quadrupole-orbitrap mass spectrometer equipped with electrospray ionization
(HESI-Q Exactive-Orbitrap MS), three carbonyl-rich products and three kinds
of organonitrates were identified in the collected SOA. Based on the HESI-Q Exactive-Orbitrap MS analysis and Fourier transform infrared spectroscopy (FTIR), the reaction mechanism of furan photooxidation
was proposed. This study demonstrates the effects of NOx and humidity on SOA
formation during the furan–NOx–NaCl photooxidation and provides new
insights into the oxidation regime and SOA composition in furan
photooxidation. The results also illustrate the importance of studying SOA
formation over a comprehensive range of environmental conditions. Only such
evaluations can induce meaningful SOA mechanisms to be implemented in air
quality models.
Contribution of horizontal and vertical advection to the formation of
small-scale vertical structures of ozone in the lower and middle
stratosphere at Fairbanks, Alaska
Authors: Yamamori Miho , Murayama Yasuhiro , Shibasaki Kazuo , Murata Isao , Sato Kaoru
Published: November 2019

Abstract. The contribution of vertical and horizontal advection to the production of small-scale vertical ozone structures was investigated using data from an ozonesonde observation performed at intervals of 3 h in Fairbanks (64.8N, 147.9W), Alaska. The dominant vertical scales of the ozone mixing ratio were determined to be 2–5 km, which were similar to those of horizontal winds and the temperature of the lower and middle stratosphere, using spectral analysis. Ozone fluctuations due to vertical advection were estimated from the potential temperature fluctuation and vertical gradient of the background ozone mixing ratio. Residual ozone fluctuations are attributed to horizontal advection. Fluctuations due to horizontal advection are dominant, as reported in previous studies. The cross-correlation of the effects of vertical and horizontal advection was also evaluated. The correlation is relatively larger at altitudes of 18–23 km and 32–33 km compared to those at other height regions. In contrast to previous studies, horizontal advection by gravity waves seems to play a dominant role in the production of small-scale ozone structures at altitudes of 32–35 km.
Extracting small deformation beyond individual station precision from dense Global Navigation Satellite System (GNSS) networks in France and western Europe
Authors: Masson Christine , Mazzotti Stephane , Vernant Philippe , Doerflinger Erik
Published: November 2019

Abstract. We use 2 decades of data from a dense geodetic network
to extract regionally coherent velocities and deformation rates in France
and neighboring western European countries. This analysis is combined with statistical
tests on synthetic data to quantify the deformation detection thresholds and
significance levels. By combining two distinct methods – Gaussian smoothing
and k-means clustering – we extract horizontal deformations with a 95 %
confidence level of ca. 0.1–0.2 mm yr−1 (ca. 0.5–1×10-9 yr−1) on
spatial scales of 100–200 km or more. From these analyses, we show that the
regionally average velocity and strain rate fields are statistically
significant in most of our study area. The first-order deformation signal in
France and neighboring western European countries is a belt of N–S to NE–SW shortening
of ca. 0.2–0.4 mm yr−1 (1–2×10-9 yr−1) in central and
eastern France. In addition to this large-scale signal, patterns of
orogen-normal extension are observed in the Alps and the Pyrenees, but
methodological biases, mainly related to GPS (Global Positioning System) solution combinations, limit
the spatial resolution and preclude associations with specific geological
structures. The patterns of deformation in western France show either
tantalizing correlation (Brittany) or anticorrelation (Aquitaine Basin)
with the seismicity. Overall, more detailed analyses are required to address
the possible origin of these signals and the potential role of aseismic
deformation.
Rethinking the Role of International Civil Service on Sustainable Development in Africa: Issues, Challenges and the Way Forward
Authors: Igbokwe-Ibeto C.J , Nnaji I.L
Published: November 2019

International civil servants are expected to provide leadership that could translate into practical gains for all human societies across the globe. They are to use their creative talents, knowledge and experience to bring these goals to pass in the life of the people of the world, particularly in developing countries. While they have embraced these goals, the extent to which they have accomplished them is still a matter of debate. Therefore, within the framework of structural-agency theory, the paper examined international civil service (ICS) and sustainable development in Africa with the aim of identifying issues, challenges and the way forward. The article employed the methods of qualitative research design as well as exploratory and descriptive perspectives. The researchers also consulted different sources to ensure quality of the article. Subsequently, relevant sources of this research were fairly and professionally scrutinised, understood and tested with the available literature for the purpose of the research. Inter alia, it included scan-reading, comprehensive and critical reading and writing down ideas. Authoritative scholarly sources were reviewed, during a desktop study. The aim was to identify the relevant publications and apply them in the research. This article argues that international civil servants are expected as a philosophy to pursue the corporate interests of the people rather than their own personal or group interests. This is why they are fondly called servants of the state and the world community respectively.  However, it appears personal and group interests have found its way into common interest. It concludes that if the ICS is to make any impact on the campaign for rapid socio-economic development of the world, the ICSs need to be proactive and interventionist in order to arrest the increasing decline in socio-economic and political development across the globe and most especially in Africa.
The Effect of Using Six Sigma Approach in Improving the Quality of Health Services in the Jordanian Ministry of Health
Authors: Al-tarawneh Ramzi Mubarak
Published: November 2019

This research aimed to examine the effect of using the Six Sigma approach with its sub-variables (management commitment and support, feedback and measurement, continuous improvement, processes and systems, human resources) on improvement quality of health services with its sub-variables (response, reliability tangibility) at Jordanian Ministry of Health ,at the top management level , to achieve the study objectives, a questionnaire was designed which consists of (48) items , used for collecting primary data from study sample (57) participant of top management level at the Ministry of Health, Accordingly the data were collected, analyzed, and hypotheses were tested using the Statistical Package for Social Sciences (SPSS), other statistical methods were used to achieve the study, The study finding revealed that: "There are a statistically significant impact at the level of significance (P≤0.050) of the Sigma Six standards and its sub -variables on the improvement of the Health services quality which presented ,by the Jordanian Ministry of Health, Based on such results the researcher recommended a number of recommendations, the most important one are :The Ministry of Health should introducing Sigma Six concept , standards, and implementing it at the top level management, and training all the employees at top management on sigma six, linking Sigma Six standards to ministry strategies, and provide all the necessary for that.

Conducting further studies that will show the positive effects of Six Sigma standards application in reducing the financial costs for health services ,and working to applying these standards to the human resources management functions.
Avaliando a Presença Espacial e Auto Presença quanto ao aprendizado no domínio afetivo
Authors: De Carvalho Thiago Viana , Machado Liliane Dos Santos
Published: November 2019

As aplicações de realidade virtual têm se expandido por diversas áreas, dentre estas, o ramo de educação, onde se destacam os serious games, jogos desenvolvidos com um propósito específico que vai além do entretenimento. Tendo em vista a capacidade dos jogos de provocar engajamento e imersão através de seus elementos, é possível deduzir que a realidade virtual pode potencializar o processo de aprendizagem do jogador.Dito isto, este trabalho objetiva avaliar a efetividade da sensação de presença no tocante ao aprendizado do jogador no domínio afetivo de aprendizagem. Para isso, pretende-se desenvolver uma aplicação em RV a partir da base conceitual do jogo Caixa de Pandora, um jogo educativo voltado a temática da violência contra a mulher.
POSTER: Desenvolvimento de um Ambiente Virtual Imersivo para Auxiliar em Práticas de Falar em Público
Authors: Stedile Carlos Gabriel Silva , Fleury Gabriel Santana , Ribeiro Marcos Wagner De Souza
Published: November 2019

Este artigo apresenta um Ambiente Virtual Imersivo para auxiliar no processo de ensino em conteúdos de oratória. A partir de uma problemática estabelecida nas dificuldades de falar em público e nos resultados apurados nas avaliações formais em disciplinas com o conteúdo de oratória ou exposição, propõe-se um ambiente que se estabelece um ambiente simulado em que o usuário possa experimentar os variados contextos da fala em público. Os resultados obtidos por meio de avaliações (System Usability Scale(SUS) e Goal/Question/Metric(GQM)) permitiram demonstrar a validação da ferramenta construída e sua efetividade no alcance dos objetivos propostos.
Simulating real robots in virtual environments using NVIDIA’s Isaac SDK
Authors: Monteiro Filipe Figueredo , Vieira-e-Silva Andre Luiz Buarque , Teixeira João Marcelo Xavier Natário , Teichrieb Veronica
Published: November 2019

Isaac SDK and Sim tools produced by NVIDIA have great potential in assisting, accelerating and even enabling, in some cases, the development of robotic applications that make use of some sort of artificial intelligence technique. This tutorial intends to show to its audience a quick theoretical background, the whole setting up process of such tools, how to integrate it to a powerful embedded system, the Jetson Nano, and a number of examples of current applications together with a good portion of possibilities enabled by those tools.
Analytical Study on Pulsed-Laser Processing for Acrylonitrile Butadiene Styrene/ PolyVinyl Chloride
Authors: XIONG Chang-Wei , FAN Si-Li , HO Ching-Yen
Published: November 2019

This study developed a model involving the energy balance and decomposition at the ablated interface due to the heat transport, optical decomposition and activation energy in Acrylonitrile Butadiene Styrene/PolyVinyl Chloride (ABS/PVC). The prediction for ablation depth obtained from this study is compared with the available experimental data. The predicted results agree with the measured data. The effects of laser processing parameters, optical and thermal properties of ABS/PVC on the variation of the laser-ablated depth with the laser fluences are also discussed. The results validate that the pulsed-laser ablation rate at the initial short period is dominated by optical penetration absorption for laser and is linearly proportional to the logarithm of the laser fluence by a ratio factor “optical absorption length” (i.e., the ablation rate follows Beer’s law at the initial short period).
Preparation and Characteristics of Microencapsulated Lauric Acid as Composite Thermal Energy Storage Materials
Authors: CHEN Yanghua , LIU Yuan , WANG Zhaohe
Published: November 2019

A novel microencapsulated phase change material was prepared by sol-gel method using lauric acid (LA) as core material and titanium dioxide (TiO2) as shell material. The composites were characterized by field emission scanning electron microscope (FE-SEM), Fourier transformation infrared spectrometer (FT-IR), differential scanning calorimeter (DSC) and thermogravimetric analyzer (TGA). The results of the FE-SEM and FT-IR indicated that LA was well coated in the shell of TiO2 and no chemical reaction occurred between them. The results of the DSC denoted that the composites with 43.5 % encapsulation ratio of the LA melted at 44.39 ℃ with the melting enthalpy of 67.54 J/g and solidified at 43.64 ℃ with the solidification enthalpy of 65.17 J/g. The results of the TGA signified that the thermal stability and fire resistance of the microcapsules were greatly enhanced under the protection barrier of TiO2. The thermal decomposition of the microencapsulated LA with TiO2 shell hardly occurred under 200 ℃. That is to say, the composites possess good thermal stability in the operating temperature range. In conclusion, the prepared microencapsulated composites can be incorporated into solar energy storage like solar air heaters and into electronic devices as heat sinks.
Self-categorization of users’ comments and ingroup influence: The moderating role of context-dependent ingroup identification
Authors: Jang Jeong-woo , Walther Joseph B.
Published: November 2019

A web-based experiment (N = 184) examined whether social identity cues embedded in users’ comments elicit ingroup bias. Participants viewed a mock Yelp.com webpage that displayed information about a local business together with four users’ comments. Consistent with self-categorization theory, viewers adopted their ingroup’s comments, but only when they identified highly with their ingroup. Further, a central message that was juxtaposed with users’ comments and shaped their focus, determined the degree of ingroup identification; viewers were more likely to identify with their ingroup when the central message dealt with an outgroup-typed (vs. ingroup-typed) topic. Finally, although an outgroup-typed central message elicited stereotypical beliefs of the outgroup’s expertise, such beliefs failed to predict viewers’ attitudes, thus lending support to the ingroup identification explanation.
Experts or Dummies? Quality of E-Book Pool and User Selections in a Consortial Demand Driven Acquisition Program
Authors: Jabaily Matthew J. , Glazier Rhonda
Published: November 2019

Academic libraries are increasingly purchasing electronic books (e-books) via demand driven acquisitions (DDA) programs.  However, there is no guarantee about the quality of DDA titles. This is especially true for consortially managed DDA pools or when pools include all titles from selected publishers. This study analyzes data from EBSCO’s GOBI acquisitions platform to assess the quality of the pool and purchased titles from the Colorado Alliance of Research Libraries (CARL) publisher-based DDA program. Results showed that most available and selected titles were appropriate for academic libraries. Popular and lower level academic titles made up a relatively small portion of the DDA pool but were selected at a proportionally higher rate than other titles. The DDA pool was weighted towards titles that had been previously purchased by few GOBI libraries, but users tended to select titles that had been purchased by more GOBI libraries. Implications of these results are discussed from the point of view of a consortium member library using the DDA program as a supplement to its broader collections of print and electronic books.
Interseccionalidade nas imagens de Pobre Preto Puto
Authors: Bernava Carla
Published: November 2019

Considerando a perspectiva de uma sociologia do cinema que, ao privilegiar a análise fílmica, preocupa-se com as especificidades da relação que se estabelece entre filme, real e espectador, esse artigo tem por objetivo discutir as possibilidades e os limites discursivos presentes na construção fílmica das intersecções entre classe, raça e sexualidade em Pobre Preto Puto (Diego Tafarel, 2016). Para tanto, em primeiro lugar, situa-se o filme em relação à como os contextos urbanos periféricos brasileiros foram historicamente construídos no interior do cinema e da atual produção queer documental do país, com vistas a problematizar as relações centro-periferia presentes no conjunto dessa produção e, em particular, no filme de Tafarel. Em segundo lugar, indaga-se sobre as possibilidades de apresentação interseccional e consubstanciada das diferenças sexuais por esse cinema, de forma a reposicionar o filme em um debate epistemológico de valorização dos saberes ditos subalternos e de abordagens interseccionais pelas Ciências Sociais.
Dossiê Cultura e Diferenças
Authors: Balieiro Fernando de Figueiredo , Pinho Patricia de Santana , Medeiros Priscila Martins
Published: November 2019

A Século XXI: Revista de Ciências Sociais, periódico cientifico do Programa de Pós-Graduação em Ciências Sociais da Universidade Federal de Santa Maria (UFSM), apresenta neste número o dossiê “Cultura e Diferenças”. Os artigos aqui reunidos trazem em comum a percepção da diferença enquanto um conjunto de representações construídas social e culturalmente, sempre imersas em relações de poder. Nesse sentido, abordar a diferença é compreendê-la enquanto elemento circunstancial, em movimento constante e sempre relacional com certos particularismos que se constituem como hegemônicos, neutros ou universais. De maneira mais específica, os artigos deste dossiê nos trazem análises atentas às experiências dissidentes e subalternas, além de refletirem sobre as circunstâncias de produção das narrativas dominantes. São reflexões que não perdem de vista a hibridez, os descentramentos e as contradições que marcam quaisquer processos de identificação social. Os textos aqui compilados transitam por temas como a produção artística na literatura e nas narrativas fílmicas periféricas; fronteiras; imigração; branquitude e formação da classe média; além da produção de teoria social.
Gnathovorax cabreirai: a new early dinosaur and the origin and initial radiation of predatory dinosaurs
Authors: Pacheco Cristian , Müller Rodrigo T. , Langer Max , Pretto Flávio A. , Kerber Leonardo , Dias da Silva Sérgio
Published: November 2019

Predatory dinosaurs were an important ecological component of terrestrial Mesozoic ecosystems. Though theropod dinosaurs carried this role during the Jurassic and Cretaceous Periods (and probably the post-Carnian portion of the Triassic), it is difficult to depict the Carnian scenario, due to the scarcity of fossils. Until now, knowledge on the earliest predatory dinosaurs mostly relies on herrerasaurids recorded in Carnian strata of South America. Phylogenetic investigations recovered the clade in different positions within Dinosauria, whereas fewer studies challenged its monophyly. Although herrerasaurid fossils are much better recorded in present-day Argentina than in Brazil, Argentinean strata so far yielded no fairly complete skeleton representing a single individual. Here, we describe Gnathovorax cabreirai, a new herrerasaurid based on an exquisite specimen found as part of a multitaxic association form southern Brazil. The type specimen comprises a complete and well-preserved articulated skeleton, preserved in close association (side by side) with rhynchosaur and cynodont remains. Given its superb state of preservation and completeness, the new specimen sheds light into poorly understood aspects of the herrerasaurid anatomy, including endocranial soft tissues. The specimen also reinforces the monophyletic status of the group, and provides clues on the ecomorphology of the early carnivorous dinosaurs. Indeed, an ecomorphological analysis employing dental traits indicates that herrerasaurids occupy a particular area in the morphospace of faunivorous dinosaurs, which partially overlaps the area occupied by post-Carnian theropods. This indicates that herrerasaurid dinosaurs preceded the ecological role that later would be occupied by large to medium-sized theropods.
Light intensity regulates phototaxis, foraging and righting behaviors of the sea urchin Strongylocentrotus intermedius
Authors: Sun Jiangnan , Chi Xiaomei , Yang Mingfang , Ding Jingyun , Shi Dongtao , Yu Yushi , Chang Yaqing , Zhao Chong
Published: November 2019

Small sea urchins Strongylocentrotus intermedius (1–2 cm of test diameter) are exposed to different environments of light intensities after being reseeded to the sea bottom. With little information available about the behavioral responses of S. intermedius to different light intensities in the environment, we carried out an investigation on how S. intermedius is affected by three light intensity environments in terms of phototaxis, foraging and righting behaviors. They were no light (zero lx), low light intensity (24–209 lx) and high light intensity (252–2,280 lx). Light intensity had obvious different effects on phototaxis. In low light intensity, sea urchins moved more and spent significantly more time at the higher intensity (69–209 lx) (P = 0.046). S. intermedius in high light intensity, in contrast, spent significantly more time at lower intensity (252–690 lx) (P = 0.005). Unexpectedly, no significant difference of movement (average velocity and total distance covered) was found among the three light intensities (P > 0.05). Foraging behavior of S. intermedius was significantly different among the light intensities. In the no light environment, only three of ten S. intermedius found food within 7 min. In low light intensity, nine of 10 sea urchins showed successful foraging behavior to the food placed at 209 lx, which was significantly higher than the ratio of the number (two of 10) when food was placed at 24 lx (P = 0.005). In the high light intensity, in contrast, significantly less sea urchins (three of 10) found food placed at the higher light intensity (2,280 lx) compared with the lower light intensity (252 lx) (10/10, P = 0.003). Furthermore, S. intermedius showed significantly longer righting response time in the high light intensity compared with both no light (P = 0.001) and low light intensity (P = 0.031). No significant difference was found in righting behavior between no light and low light intensity (P = 0.892). The present study indicates that light intensity significantly affects phototaxis, foraging and righting behaviors of S. intermedius and that ~200 lx might be the appropriate light intensity for reseeding small S. intermedius.
An Approach to Drug Stability Studies and Shelf-life Determination
Authors: Tembhare Ekta , Gupta Krishna Radheshyam , Umekar Milind Janrao
Published: November 2019

The main objective of carrying out stability studies of the drug product is to establish shelf life of drug during storage. Stability of drug is defined as “The capability of a particular formulation in a specific container/closed system, to remain within its physical, chemical, microbiological, therapeutic, and toxicological specifications throughout its shelf life”. As mentioned in the International Conference on Harmonization (ICH) guideline Q1A (R2), stability studies are commonly the activity on the critical path to regulatory filing and approval. Stability studies are of different types and different methods are useful for the determination of stability like real-time stability testing, accelerated stability testing, retained sample stability testing and cyclic temperature stress testing. pH and temperature are the main factors influencing the stability of the drug. The pH-rate profile (log(k)vs pH) is the pH dependence of the specific rate constant of degradation of compounds. Forced degradation includes deterioration of new drug substances and products at more severe conditions than the accelerated conditions and it indicates the accuracy of stability-indicating methods. The different conditions applied during the forced degradation include hydrolytic, oxidation, photolytic and thermal stress etc. The techniques utilized for evaluation of stability studies can be LC-MS/MS, HPLC-DAD, HPLC-MS, HPLC-UV, HPTLC, TLC, LC-NMR etc. amongst them some techniques shows high sensitivity and resolution power to establish more effective stability-indicating method while for shelf life estimation of drugs and products the different methods mentioned are FDA’s method, the direct method, inverse method, simulation results and Garret and Carper method. Thus stability testing of pharmaceutical products inputs specific scheme in the evolution of a new drug as well as new formulation.
Crystal structure of the catalytic D2 domain of the AAA+ ATPase p97 reveals a putative helical split‐washer‐type mechanism for substrate unfolding
Authors: Stach Lasse , Morgan Rhodri Marc , Makhlouf Linda , Douangamath Alice , von Delft Frank , Zhang Xiaodong , Freemont Paul S.
Published: November 2019

Several pathologies have been associated with the AAA+ ATPase p97, an enzyme essential to protein homeostasis. Heterozygous polymorphisms in p97 have been shown to cause neurological disease, while elevated proteotoxic stress in tumours has made p97 an attractive cancer chemotherapy target. The cellular processes reliant on p97 are well described. High‐resolution structural models of its catalytic D2 domain, however, have proved elusive, as has the mechanism by which p97 converts the energy from ATP hydrolysis into mechanical force to unfold protein substrates. Here, we describe the high‐resolution structure of the p97 D2 ATPase domain. This crystal system constitutes a valuable tool for p97 inhibitor development and identifies a potentially druggable pocket in the D2 domain. In addition, its P61 symmetry suggests a mechanism for substrate unfolding by p97.

Database

The atomic coordinates and structure factors have been deposited in the PDB database under the accession numbers 6G2V, 6G2W, 6G2X, 6G2Y, 6G2Z and 6G30.
Inconsistencies abound in how states handle MAT access under Medicaid
Authors: Enos Gary
Published: November 2019

A report commissioned by Congress suggests that while states have made some progress in lifting barriers to medication treatment access for Medicaid beneficiaries with opioid use disorder (OUD), some important obstacles to expanded access remain. Among the inconsistencies in state regulation, the report found a decreasing tendency to assign preferred status to medication‐assisted treatment (MAT) drugs at the same time that prior authorization requirements are declining, as well as more frequent restrictions on MAT for OUD than on medications to treat alcohol use disorders.
Enhancing Triple Negative Breast Cancer Immunotherapy by ICG‐Templated Self‐Assembly of Paclitaxel Nanoparticles
Authors: Feng Bing , Niu Zifei , Hou Bo , Zhou Lei , Li Yaping , Yu Haijun
Published: November 2019

Combination cancer immunotherapy has shown promising potential for simultaneously eliciting antitumor immunity and modulating the immunosuppressive tumor microenvironment (ITM). However, combination immunotherapy with multiple regimens suffers from the varied chemo‐physical properties and inconsistent pharmacokinetic profiles of the different therapeutics. To achieve tumor‐specific codelivery of the immune modulators, an indocyanine green (ICG)‐templated self‐assembly strategy for preparing dual drug‐loaded two‐in‐one nanomedicine is reported. ICG‐templated self‐assembly of paclitaxel (PTX) nanoparticles (ISPN), and the application of ISPN for combination immunotherapy of the triple negative breast cancer (TNBC) are demonstrated. The ISPN show satisfied colloidal stability and high efficacy for tumor‐specific codelivery of ICG and PTX through the enhanced tumor permeability and retention effect. Upon laser irradiation, the ICG component of ISPN highly efficiently induces immunogenic cell death of the tumor cells via activating antitumor immune response through photodynamic therapy. Meanwhile, PTX delivered by ISPN suppresses the regulatory T lymphocytes (Tregs) to combat ITM. The combination treatment of TNBC with ISPN and αPD‐L1‐medaited immune checkpoint blockade therapy displays a synergistic effect on tumor regression, metastasis inhibition, and recurrence prevention. Overall, the ICG‐templated nanomedicine may represent a robust nanoplatform for combination immunotherapy.
Probing the Impedance of a Biological Tissue with PEDOT:PSS‐Coated Metal Electrodes: Effect of Electrode Size on Sensing Efficiency
Authors: Koutsouras Dimitrios A. , Lingstedt Leona V. , Lieberth Katharina , Reinholz Jonas , Mailänder Volker , Blom Paul W. M. , Gkoupidenis Paschalis
Published: November 2019

Electrodes coated with poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) have been employed to measure the integrity of cellular barriers. However, a systematic experimental study of the correlation between tissue integrity and impedance of the sensing device has not yet been conducted. Using impedance spectroscopy, how the impedance ratio of the biological tissue to the recording device affects the recording ability of the latter is investigated. PEDOT:PSS‐coated electrodes of various dimensions are employed and the effect of their size to their sensing efficiency is examined. The biotic/abiotic ensemble is modeled with a simple equivalent circuit and an analytical expression of the total impedance as a function of frequency is extracted. The results reveal a critical impedance ratio of the biological tissue to the sensor which allows for efficient sensing of the tissue integrity. This work provides the ground rules for improved impedance‐based biosensors with optimized sensitivity.
Association of gastric acid suppressants with the development of spontaneous bacterial peritonitis in cirrhotic patients with ascites
Authors: Teng Shih‐Lun , Hsu Che‐Han , Hsu Chia‐Chun , Shin Jeng‐Shiann , Huang Jen‐Chieh
Published: November 2019

The study aimed to characterize the association of gastric acid suppressants (GAS) with the development of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites. A retrospective case controlled study from January 2013 to December 2017 at Cheng‐Ching General Hospital was conducted. We included patients with a diagnosis of liver cirrhosis with ascites, divided into those with and without SBP. SBP was defined by ascitic fluid polymorphonuclear cell level. GAS users were patients who received GAS daily for more than 7 days in the 90 days before admission. Of 229 cirrhotic patients enrolled, 60 had SBP and 169 did not. The groups differed significantly in albumin (P = .045) and total bilirubin (P = .016) levels; in international normalized ratio (P = .007) and proton pump inhibitor (PPI) use (P = .021); but not in histamine‐2 receptor antagonist (H2RA) use. Multivariate analysis identified PPI use as the only independent risk factor for SBP development (odds ratio 2.101, 95% confidence interval 1.122‐3.935, P = .02). PPIs but not H2RAs may increase the incidence of SBP in cirrhotic patients with ascites. Prescribing PPIs in cirrhotic patients should be done carefully, for the minimal effective treatment duration.
OHS education and safety training of teenage workers in Iceland
Authors: Einarsdóttir Margrét , Snorradóttir Ásta
Published: November 2019

Background

We sought to investigate the extent and quality of occupational health and safety (OHS) education and safety training of Icelandic teenagers.

Methods

Mixed methods were used to obtain data. Initially, 12 group and 7 individual interviews with a total of 45 teenagers were conducted. Supplemental qualitative data was collected to corroborate the interviews. Following this, a survey was sent to a sample of 2800 13 to 19‐year‐olds, randomly selected from Registers Iceland.

Results

The response rate was 48.6% (N = 1339). Severe inadequacy in the quality and quantity of both OHS education and safety training was found. In total, 30% received OHS education at school and 14% obtained safety training at work. OHS education was considered unsystematic, and the safety training low engagement. Participants noted that safety training was especially inadequate in jobs in the retail sector and restaurants.

Conclusions

OHS education needs to be taught systematically within all levels of the Icelandic school system, and authorities should be more active in educating employers on their responsibilities on health and safety at work.
An overview of existing mesothelioma registries worldwide, and the need for a US Registry
Authors: van Gerwen Maaike , Alpert Naomi , Flores Raja , Taioli Emanuela
Published: November 2019

The association between asbestos exposure, mainly in occupational settings, and malignant mesothelioma has been well established; this has prompted several countries to establish mesothelioma epidemiologic surveillance programs often at the request of national agencies. This review compares currently existing mesothelioma registries worldwide to develop a concept model for a US real‐time case capture mesothelioma registry. Five countries were identified with a mesothelioma specific registry, including Italy, France, UK, Australia, and South Korea. All, except the UK, used interviews to collect exposure data. Linkage with the national death index was available or was in future plans for all registries. The registries have limited information on treatment, quality of life, and other patient‐centered outcomes such as symptoms and pain management. To thoroughly collect exposure data, “real‐time” enrollment is preferable; to maximize the capture of mesothelioma cases, optimal coverage, and a simplified consent process are needed.
Designing of internal model control proportional, integral, and derivative controller with second‐order filtering for lag‐ and delay‐dominating processes based on suitable dead time approximation
Authors: Nath Ujjwal Manikya , Dey Chanchal , Mudi Rajani K.
Published: November 2019

In practice, majority of the industrial chemical processes contain considerable dead time and significant process lag. Depending on the value of dead time to time constant ratio, industrial processes can be classified as lag dominating and delay dominating in nature. Here, an attempt has been made to find out an improved dead time estimation technique from the available methodologies like Taylor series and Pade's approximation relations so that a more accurate process model can be obtained and, consequently, an enhanced model‐based internal model control based proportional, integral, and derivative (IMC‐PID) controller may be designed. In addition, to ensure an improved closed loop performance, a second‐order filter is incorporated in IMC‐PID structure where damping term of the filter is calculated from dead time to time constant ratio of the concerned process. Efficacy of the proposed scheme is verified through simulation study on first‐order plus dead time, second‐order plus dead time, higher order, and nonminimum phase processes in comparison with recently reported model‐based PID settings. In addition to simulation study, a real‐time experimental verification is also made on a level control loop under transient and steady state operating phases.
Sex and Ontogenetic Variation in the Crest of Numida meleagris: Implications for Crested Vertebrates
Authors: Angst Delphine , Barnoud Jonathan , Cornette Raphaël , Chinsamy Anusuya
Published: November 2019

Crested vertebrates are known from a wide variety of modern and fossil taxa, however, the actual formation and function of the crest is still debatable. Among modern birds, the globally distributed guinea fowl (Numida meleagris) is characterized by having a cranial bony crest (overlain by keratin), but surprisingly little is known about its development. Here, we studied the crest of 202 wild guinea fowl from the same population, using anatomical measurements as well as 2D‐morphometry. Our results show that juveniles have smaller skulls than adults and have smaller, simpler crests that are visible even in very young individuals. Among adults, female skulls are smaller than males, and they have smaller, simpler shaped crests, which permit a discrimination between the sexes of 93% when the keratin is preserved with the bony crest, and of 89% when only the bony crest is available. By extrapolation, these results confirm that the crest can be used as an ontogenetic character, as well as for sex discrimination in the fossil record. Our results also show that the overlying keratin does not always mimic the underlying bony crest, which should be considered when reconstructing extinct crested vertebrates. Anat Rec, 303:1018–1034, 2020. © 2019 American Association for Anatomy
Physicochemical characteristics of human IgG Fc fragments that expose regulatory rheumatoid factor neoepitopes and may show promise as antirheumatic agents
Authors: Sidorov Alexandr , Beduleva Liubov , Menshikov Igor , Terentiev Alexey , Cherepanov Igor
Published: November 2019

Previously, we showed that immunoglobulin G (IgG) Fc fragments can expose neoepitopes specific to antibodies that were named regulatory rheumatoid factor (regRF). RegRF confers resistance to experimental autoimmune diseases. Immunization of rats with rat Fc fragments exposing neoepitopes recognized by regRF reduces the symptoms of collagen‐induced arthritis. Therefore, IgG Fc fragments that expose neoepitopes recognized by regRF are promising antirheumatic agents and regRF‐producing lymphocytes are potential therapeutic biotargets. The purpose of this study was to elucidate the physicochemical features of human IgG Fc fragments that are associated with the presence of immunosuppressive neoepitopes recognized by regRF. It was found that the acquisition of neoepitopes recognized by regRF is associated with a reduction of the hinge disulfide bonds and conformational changes in the Fc fragment domains. Alkylation of thiol groups in the hinge leads to loss of the epitopes. Therefore, the neoepitopes recognized by regRF may form directly in the hinge when interchain disulfide bonds are reduced or in the region of the CH2 domain as part of the conformational changes caused by the reduction of the interchain disulfide bonds in the hinge. Species‐specificity studies of neoepitopes recognized by regRF revealed that human and rat neoepitopes recognized by regRF are cross‐reactive.