bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical analysis of induction heating in high-temperature epitaxial growth system
Authors: Mei Shuzhe , Wang Quan , Hao Meilan , Xu Jiankai , Yin Haibo , Xiao Hongling , Feng Chun , Jiang Lijuan , Wang Xiaoliang , Liu Fengqi , Xu Xiangang , Wang Zhanguo
Published: August 2018

The temperature uniformity and heating efficiency in a high-temperature epitaxial growth system were investigated by modeling and simulating. The finite element method (FEM) was used to calculate the distribution of magnetic field and temperature field in the reactor of growth system. The simulation results showed that due to the skin effect and heat conduction in the conventional susceptor, the temperature distribution of the wafer on the susceptor is not uniform. However, the temperature uniformity of the wafer can be greatly improved by adding an air gap below the wafer. The existence of air gap effectively reduced the temperature on the center of the wafer, and the effect of its radius on temperature uniformity was studied. By calculating different frequencies and coil currents, the temperature and heating rate in the reactor with modified susceptor were investigated. The results indicated that higher temperature and faster heating rate can be obtained by increasing heating frequency and coil current. However, both lower and higher frequency will bring worse temperature uniformity.
Modeling large permittivity of poly(vinylidenefluoride-co-trifluoroethylene) and nanospring single-walled carbon nanotube-polyvinylpyrrolidone nanocomposites
Authors: Lee Yun Jae , Kim Jung Hyuk , Ham Sora , Ju Byeong-Kwon , Choi Won Kook
Published: August 2018

Highly dispersible nanospring single-walled carbon nanotubes (NS-CNTs) were incorporated in a P(VDF-TrFE) copolymer with up to 15 wt.% of nanofiller. The relative dielectric constant (K) of the polymer nanocomposite at 1 kHz was greatly enhanced from 12.7 to 62.5 at 11 wt.% of NS-CNTs, corresponding to a 492% increase over that of pristine P(VDF-TrFE) with only a small dielectric loss tangent (D) of 0.1. Based on two theoretical models, the Bruggeman equation and self-consistent effective medium theory (SC-EMT), experimental permittivity data for the P(VDF-TrFE) and NS-CNTs nanocomposites were simulated to estimate the dielectric constant of the NS-CNTs while changing both the shape of the nanofillers and the volume fraction of the interface when increasing the number of NS-CNTs in piled layers of P(VDF-TrFE). The number of NS-CNTs layers was counted from HR-TEM images to calculate the interfacial volume fraction, and used to infer the Eshelby tensor of the NS-CNTs in the SC-EMT model. The experimental dielectric constants of the composite films fit the Bruggeman equation and SC-EMT theory well for dielectric constants k=240–360, showing that the NS-CNTs nanofillers may be considered electrically semiconductive.
Conductive atomic force microscopy studies of charged domain walls in KTiOPO4
Authors: Lindgren G. , Canalias C.
Published: August 2018

We study the conductive properties of charged domain walls in KTiOPO4 using conductive atomic force microscopy. We show that the region of increased conductivity at the domain wall broadens when the wall is in motion, extending from the initial wall position to the final wall position. When wall motion stops, the conductive region attains a narrow width. The magnitude of the conductivity of charged domain walls is four times larger than that of the surrounding domains, as is the case at stationary wall. We investigate the impact of the scanning-angle on the domain wall conductivity and the wall motion.
Coral colonies in the eastern tropical Pacific: predation by Acanthaster cf. solaris
Authors: Rodríguez-Vilalobos J. C. , Ayala-Bocos A.
Published: August 2018

The crown of thorns (CoTS; Acanthaster cf. solaris) have not been reported as an actual threat to reefs in the Gulf of California; however, in the Espiritu Santo Archipelago National Park, we have evidenced massive predation over scleractinian corals. Its abundance is now over outbreaks threshold value and it is higher than historical records
Phylogeographic evidence for evolutionary refugia in the Gulf sandstone ranges of northern Australia
Authors: Noble Catherine , Laver Rebecca J. , Rosauer Dan F. , Ferrier Simon , Moritz Craig
Published: August 2018

Locating and protecting climate change refugia is important to conserving biodiversity with accelerating climate change. Comparative phylogeographic analysis provides an effective tool for locating such refugia, as long-term retention of one or more populations within a refugial landscape will generate unique genetic lineages. The ranges of the western Gulf region of northern Australia are thought to represent a significant arid-zone refugium, in which case low-dispersal organisms should have strong phylogeographic structure across the region. To test for this, we conducted extensive sampling of three species of Gehyra geckos and analysed diversity for mitochondrial DNA and eight nuclear loci. These analyses revealed congruent and high phylogeographic diversity, especially, but not exclusively, in rock-restricted species. This finding, and other recent phylogeographic evidence, demonstrates that these topographically variable landforms have enabled persistence of ecologically diverse vertebrate species through the climate changes of the late Pleistocene. Identification of this relatively under-protected region as a significant climate change refugium points to the need to expand protected areas in this region and to invest in ecological management across existing National Parks and Indigenous Protected Areas.
The effect of playing status, maturity status, and playing position on the development of match skills in elite youth football players aged 11–18 years: A mixed‐longitudinal study
Authors: Saward Chris , Morris John G. , Nevill Mary E. , Sunderland Caroline
Published: August 2018

This mixed‐longitudinal study examined the development of match skills in elite male youth footballers (aged 11–18 years), while considering the effect of playing status, maturity status, and playing position. Across two seasons, 126 elite male youth footballers were assessed in 1–10 competitive matches (401 player‐matches). For each match, the on‐the‐ball actions of each player were recorded using a notation system. The match skills observed were frequencies of successful passes, on‐target shots, dribbles, crosses, clearances, and tackles/blocks/interceptions. Multilevel Poisson analysis was used to model the development of players, with regard to each match skill. Modelling revealed significant (p < .05) age‐related changes in the frequency of several match skills. That is, dribbles increased, on‐target shots, crosses and tackles/blocks/interceptions decreased, whereas changes in successful passes were position‐specific. Players retained by an academy performed more dribbles compared to released players (p < .05) (e.g. retained vs. released 18‐year‐old centre forward = 4.1 vs. 2.0 dribbles per hour), and retained defenders performed more tackles/blocks/interceptions than released defenders (p < .05) (e.g. retained vs. released 18‐year‐old, on‐time maturing centre back = 12.5 vs. 10.2 tackles/blocks/interceptions per hour). Moreover, compared to on‐time maturing players, early maturing players performed more tackles/blocks/interceptions (p < .05) (e.g. on‐time vs. early maturing retained 18‐year‐old centre back = 12.5 vs. 15.2 tackles/blocks/interceptions per hour). Playing position affected all match skills (p < .05). The developmental profiles of match skills presented here may support experts in identifying and developing talented footballers across a wide age range, while considering the influence of maturity status and playing position.
Effects of low volume isometric leg press complex training at two knee angles on force‐angle relationship and rate of force development
Authors: Bogdanis Gregory C. , Tsoukos Athanasios , Methenitis Spyridon K. , Selima Elisavet , Veligekas Panagiotis , Terzis Gerasimos
Published: August 2018

This study compared knee angle‐specific neuromuscular adaptations after two low‐volume isometric leg press complex training programmes performed at different muscle lengths. Fifteen young males were divided into two groups and trained three times per week for 6 weeks. One group (n = 8) performed 5–7 sets of 3 s maximum isometric leg press exercise, with 4 min recovery, with knee angle at 85° ± 2° (longer muscle‐tendon unit length; L‐MTU). The other group (n = 7) performed the same isometric training at a knee angle of 145° ± 2° (180° = full extension; shorter muscle‐tendon unit length; S‐MTU). During the recovery after each set of isometric exercise, participants performed two CMJ every minute, as a form of complex training. Maximum isometric force (MIF) and rate of force development (RFD) were measured over a wide range of knee angles. Countermovement jump (CMJ) performance and maximum half‐squat strength (1RM) were also assessed. Training at S‐MTU induced a large increase of MIF (22–58%, p < 0.02) and RFD (18–43%, p < 0.05 to 0.001) at knee angles close to the training angle and resulted in a 14° ± 9° shift of the force vs. knee joint angle relationship towards extended knee joint angles (p = 0.001). In contrast, training at L‐MTU, resulted in a moderate and similar (≈12.3%, p = 0.028) improvement of force at all knee angles. CMJ performance and 1RM were equally increased in both groups after training by 10.4% ± 8.3% and 7.8% ± 4.7% (p < 0.001), respectively. Low‐volume maximal isometric leg‐press complex training at S‐MTU causes angle‐specific adaptations in isometric strength and RFD, while dynamic muscle performance is independent of muscle length during training.
TRCirc: a resource for transcriptional regulation information of circRNAs
Authors: Tang Zhidong , Li Xuecang , Zhao Jianmei , Qian Fengcui , Feng Chenchen , Li Yanyu , Zhang Jian , Jiang Yong , Yang Yongsan , Wang Qiuyu , Li Chunquan
Published: August 2018

In recent years, high-throughput genomic technologies like chromatin immunoprecipitation sequencing (ChIp-seq) and transcriptome sequencing (RNA-seq) have been becoming both more refined and less expensive, making them more accessible. Many circular RNAs (circRNAs) that originate from back-spliced exons have been identified in various cell lines across different species. However, the regulatory mechanism for transcription of circRNAs remains unclear. Therefore, there is an urgent need to construct a database detailing the transcriptional regulation of circRNAs. TRCirc (http://www.licpathway.net/TRCirc) provides a resource for efficient retrieval, browsing and visualization of transcriptional regulation information of circRNAs. The current version of TRCirc documents 92 375 circRNAs and 161 transcription factors (TFs) from more than 100 cell types and together represent more than 765 000 TF–circRNA regulatory relationships. Furthermore, TRCirc provides other regulatory information about transcription of circRNAs, including their expression, methylation levels, H3K27ac signals in regulation regions and super-enhancers associated with circRNAs. TRCirc provides a convenient, user-friendly interface to search, browse and visualize detailed information about these circRNAs.
Corruption and Contractors in the Atlantic World, 1754–1763
Authors: Graham Aaron
Published: August 2018

This article examines the reality of corruption among contractors in North America during the French and Indian War (1754–63), one of the key grievances in the prologue to the Revolution, and argues that contemporaries were mistaken about its ubiquity. The letters of financial contractors remitting money to their agents show that they saw it as a patriotic duty rather than just a commercial transaction, and frequently went beyond the letter of the contract in order to maintain the flow of money to the British army in North America. Why did corruption therefore appear so dangerously prevalent? Military finance was inherently complex and opaque, and open to misinterpretation. Although shared political loyalties held together the contractors and their agents and helped to police their behaviour, other imperial and colonial components of the British state had different priorities and therefore saw the public service in different ways. Disagreements over military finance were misconstrued by both sides as obstruction, and as evidence of outright corruption, which served as a polemical tool to discredit alternative views of the public interest. Corruption therefore appeared so prevalent, and obtained such political power, because of misunderstandings and contests within the fabric of the British state about the best direction for public policy.
Alliance management knowledge and alliance performance: unveiling the moderating role of the dedicated alliance function
Authors: Russo Angeloantonio , Vurro Clodia
Published: August 2018

This study attempts to increase the understanding of how different solutions to build alliance management capability influence alliance performance. We propose that both reliance on the informal accumulation of alliance experience (i.e., tacit alliance management knowledge, AMK) and articulation of alliance know-how in the form of usable guidelines, checklists, or manuals (i.e., codified AMK) have an inverted U-shaped influence on alliance performance. Additionally, we investigate the moderating role of having the dedicated alliance function (DAF) on the curvilinear relationships between reliance on AMK and performance. Based on a sample of 113 large firms involved in strategic alliances, we find support for the inverted U-shaped relationship between reliance on tacit and codified AMK and alliance performance. Moreover, our results indicate that the DAF has a positive impact on the deployment of AMK. The DAF turns into improved performance when the reliance on experiential learning and the codification of AMK are both limited. Moreover, the DAF also reduces the potential downside effects of relying on higher levels of both types of AMK. Finally, DAF diversity, in terms of educational, functional, and tenure heterogeneity of its members, emerges as relevant to achieve effective alliance know-how collection and deployment for superior alliance performance.
Comparison of Six Artificial Diets for Western Corn Rootworm Bioassays and Rearing
Authors: Meihls Lisa N , Huynh Man P , Ludwick Dalton C , Coudron Thomas A , French B Wade , Shelby Kent S , Hitchon Andrea J , Smith Jocelyn L , Schaafsma Art W , Pereira Adriano E , Hibbard Bruce E
Published: August 2018

The western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), is considered the most important maize (Zea mays L.) pest in the U.S. Corn Belt. Bioassays testing susceptibility to Bacillus thuringiensis Berliner (Bt) and other toxins of corn rootworm larvae often rely on artificial diet formulations. Successful bioassays on artificial diet for corn rootworm have sometimes been challenging because of microbial contamination. Toward the long-term goal of developing a universal artificial diet for western corn rootworm larvae, we compared larval survival, dry weight, and percentage of molt in 10-d bioassays from six current diets of which we were aware. In addition, as part of longer term rearing efforts, we recorded molting over an extended period of development (60 d). Six different artificial diets, including four proprietary industry diets (A, B, C, and D), the first published artificial diet for western corn rootworm (Pleau), and a new diet (WCRMO-1) were evaluated. Western corn rootworm larval survival was above 90% and contamination was 0% on all diets for 10 d. Diet D resulted in the greatest dry weight and percentage molting when compared with the other diets. Although fourth-instar western corn rootworm larvae have not been documented previously (only three instars have been previously documented), as many as 10% of the larvae from Diet B molted into a fourth instar prior to pupating. Overall, significant differences were found among artificial diets currently used to screen western corn rootworm. In order for data from differing toxins to be compared, a single, reliable and high-quality western corn rootworm artificial diet should eventually be chosen by industry, academia, and the public as a standard for bioassays.
The first photometric investigation and period study of two W UMa-type binary systems: EF CVn and EH CVn
Authors: Xia Qi-Qi , Li Kai , Chen Xu , Guo Di-Fu , Gao Dong-Yang
Published: August 2018

By analyzing the V, Rc, and Ic light curves of the two neglected W UMa-type binaries EF CVn and EH CVn using the Wilson–Devinney code, we have discovered that EF CVn is a median contact binary while EH CVn is a shallow contact binary, and they are both W-subtype binary systems. The mass ratio and fillout factor of EF CVn are q = 3.493 ± 0.063 and f = 32.0% ± 12.9%, respectively. Those of EH CVn are q = 3.331 ± 0.052 and f = 19.2% ± 10.9%, respectively. The addition of a dark spot on the secondary star is used to interpret the asymmetric light curves of EF CVn. An orbital period analysis of EF CVn indicates that there is a cyclic oscillation with an amplitude of 0.0064 d and a period of 15.65 yr, accompanied by a continuous increase at a rate of dp/dt = 4.52 × 10−7 d yr−1. The periodic oscillation can reasonably be explained by the light travel-time effect of an additional component. The secular increase is probably generated by conservative mass transfer from the primary star to the secondary star. Meanwhile, an analysis of the orbital period of EH CVn was also performed. A long-term period decrease at a rate of dp/dt = −5.20 × 10−8 d yr−1 was discovered; this is possibly interpreted as caused by mass transfer from the more massive component to the less massive component.
Barriers and facilitators of access to biological material for international research: The role of institutions and networks
Authors: Fusi Federica , Welch Eric W , Siciliano Michael
Published: August 2018

In recent years, international and national policies have intensified monitoring and control over the access, exchange, and use of biological materials. New regulative institutions addressing concerns about ownership and safety, as well as fairness and equity, are increasingly intermingled with informal practices and norms of exchange, raising the barriers to access biological materials that scientists face. Drawing from unique survey-based ego-centric network data collected from US and non-US scientists engaged in international collaborative research at the USAID Feed the Future Innovation Labs, this article investigates how regulative institutions, organizational and regional norms (meso-level institutions), and interpersonal networks facilitate or challenge access to biological materials for research. Our results show that while regulative institutions hinder access, meso-level institutions are important access facilitators in an international context. Network ties reduce the delays and blockages to access of biological material, but they do not eliminate them.
Cladistic analysis of the tribe Eburiini Blanchard, 1945 and revalidation of the tribe Dychophyiini Gistel, 1848 (Coleoptera: Cerambycidae)
Authors: Botero Juan Pablo , Monné Marcela L
Published: August 2018

Eburiini is currently composed of 22 genera and 262 species, with a geographical distribution restricted to the Americas. Herein, we present a cladistic analysis of Eburiini and its genera, using a matrix with 82 terminal taxa, 52 from the ingroup (including representatives of all recognized genera) and 30 from the outgroup, and 105 characters of the adult morphology. The matrix was analysed under implied weights, and the tribe was not recovered as monophyletic. In order to recover the monophyly of the tribe, two genera of Heteropsini, Heterops and Eburiola, were transferred to Eburiini. The transfer of Heterops, type genus of Heteropsini, results in these two tribes being considered synonyms, with the name Eburiini having priority. The tribe Dychophyiini was resurrected to include the genera that were allocated to Heteropsini and were not transferred to Eburiini. The subgenus Eburia (Eleutho) was recovered as monophyletic and is herein elevated to genus rank. The genera Opades and Pantomallus are synonymized. The species Eburia sordida and Eburia fuliginea were transferred to Pantomallus, recovering the monophyly of the genus. With the synonymy of Opades, the transfer of the genera Heterops and Eburiola, and the new status of Eleutho, Eburiini is composed of 24 genera and 268 species.
Pectobacterium carotovorum subsp. brasiliense Causes Soft Rot and Death of Neobuxbaumia tetetzo in Zapotitlan Salinas Valley, Puebla, Mexico
Authors: Mejía-Sánchez Dimas , Aranda-Ocampo Sergio , Nava-Díaz Cristian , Teliz-Ortiz Daniel , Livera-Muñoz Manuel , De La Torre-Almaráz Rodolfo , Ramírez-Alarcón Samuel
Published: August 2018

Neobuxbaumia tetetzo (Coulter) Backeberg (tetecho) is a columnar cactus endemic to Mexico. Tetecho plants, flowers, fruits, and seeds play an important role in the semiarid ecosystem, as they serve as a refuge and food for insects, bats, and birds, and are widely used by ethnic groups since pre-Hispanic times. Tetecho is affected by a soft rot that damages the whole plant and causes its fall and disintegration. Eight bacterial colonies of similar morphology were isolated from plants showing soft rot and inoculated in healthy tetecho plants, reproducing typical symptoms of soft rot 9 days after inoculation. Ten representative isolates were selected for phenotypic and genetic identification using 16s rDNA, IGS 16S-23S rDNA, and rpoS genes and for pathogenicity tests on several members of the cactus family and other plants. Based on the results, these bacterial isolates were identified as Pectobacterium carotovorum subsp. brasiliense. Inoculation of this bacteria caused soft rot in different cacti, fruits, leaves, and roots of other plants. This is the first report of the subspecies brasiliense of P. carotovorum causing soft rot and death in cacti in the world and the first report of this subspecies in Mexico.
Using the Hybrid Operating Room in Thoracic Surgery
Authors: Schroeder Carsten , Chung Jane M. , Mitchell Andrew B. , Dillard Thomas A. , Radaelli Alessandro G. , Schampaert Stephanie
Published: August 2018

We describe the integration of the hybrid operation room cone-beam computed tomography (CT) scan technology into the practice of general thoracic surgery. The combination of the following three techniques: (1) cone-beam CT scan augmented navigational bronchoscopy, (2) cone-beam CT-guided percutaneous biopsy and/or fiducial placement, and (3) fiducial or image-guided video-assisted thoracic surgery resection, into a single-stage, single-provider procedure allows for diagnosis and treatment in one setting. Rapid on-site evaluation of cytological or pathology specimens is key to this “all-in-one” approach. The time from diagnosis to curative treatment can significantly be reduced using the hybrid operation room technology, leading to decreased upstaging, increased survival and facilitating the otherwise difficult intraoperative detection and resection of small and deeper lesions. Not only does this benefit the overall thoracic healthcare of the community but also provides a cost-effective paradigm for the institution.
Rheumatoid Arthritis-Associated Orbital Vasculitis
Authors: Weber Adam C. , Shetlar Debra J. , Yen Michael T.
Published: August 2018

A patient with a history of rheumatoid arthritis presented with bilateral orbital lesions while on abatacept. Biopsy of the lesions yielded pathologic assessment showing vasculitis with a mixed inflammatory infiltrate notable for numerous eosinophils. Despite initial improvement on cyclophosphamide therapy, she developed progression of the orbital lesions and lesions elsewhere on her body. All serologic studies were normal except for increased levels of rheumatoid factor and eosinophilia. The patient underwent a second biopsy, which was consistent with her initial pathology. The patient was started on high-dose mycophenolate mofetil treatment with a good response. After 1 year of treatment, the patient’s lesions have nearly completely resolved. This patient illustrates the diagnostic and therapeutic challenges encountered when treating orbital vasculitis. Furthermore, this case shows the importance of not categorizing vasculitis with unclear etiology under the umbrella diagnosis of atypical granulomatosis with polyangiitis. This patient did not exhibit the serologic or pathologic characteristics of granulomatosis with polyangiitis, and she did not respond to treatment as would be expected for granulomatosis with polyangiitis. Maintaining an open approach to diagnosis and treatment was crucial in obtaining a favorable outcome for this patient.
Sport Preparticipation Screening for Asymptomatic Atlantoaxial Instability in Patients With Down Syndrome
Authors: Tomlinson Christopher , Campbell Alastair , Hurley Alison , Fenton Eoin , Heron Neil
Published: August 2018

Down syndrome (DS) is a clinical syndrome comprising typical facial features and various physical and intellectual disabilities due to extra genetic material on chromosome 21, with one in every 1000 babies born in the United Kingdom affected. Patients with Down syndrome are at risk of atlantoaxial instability (AAI). Although AAI can occur in other conditions, such as rheumatoid arthritis, this position statement deals specifically with patients with DS and asymptomatic AAI. Atlantoaxial instability, also referred to as atlantoaxial subluxation, is defined as increased movement between the first (atlas) and second (axial) cervical vertebra joint articulation, the atlantoaxial joint. Atlantoaxial instability is reported to occur in 6.8% to 27% of the DS population, although this varies depending on the age of the patients whom you are screening. Less than 1% to 2% of these patients are then thought to later develop symptomatic AAI, although the natural history and progression of AAI is not well understood. The risks associated with AAI are neurological injury from excessive movement of the cervical vertebra impinging on and then damaging the spinal cord, although the risk of this during sporting activities is extremely rare. Clearly, physical activity and sports participation for patients with DS has many biological, psychological, and social benefits, and the Faculty of Sport and Exercise Medicine (FSEM), United Kingdom, wishes to promote safe physical activity and sport for all. The FSEM, United Kingdom, has therefore produced a statement regarding sport preparticipation screening for asymptomatic AAI in patients with DS.
The catalytic role of iodine excess in loss of homeostasis in autoimmune thyroiditis
Authors: Duntas Leonidas H.
Published: August 2018

Purpose of review

To review the latest developments concerning the role of iodine in the pathophysiology of autoimmune thyroiditis.

Recent findings

Recent studies have provided evidence that in areas with excess iodine intake, increased incidence of autoimmune thyroiditis marked by high titers of thyroid peroxidase and thyroglobulin antibodies has occurred. Investigations in the NOD.H2h4 mouse, a strain prone to AIT, showed that they are better adapted to the Wolff–Chaikoff effect.

To provide an overview of the studies conducted during the last few years implicating iodine in the development and manifestation of autoimmune thyroiditis.
Nontraditional Students’ Perceptions of Marginalization in Baccalaureate Nursing Education
Authors: Englund Heather M.
Published: August 2018

Background

Despite the continued efforts to diversify the population of nursing students in the United States, marginalization and attrition remain significant issues for nontraditional students.

Purpose

The purpose of this study was to investigate the relationship between marginality and nontraditional student status in nursing students enrolled in a baccalaureate nursing program in Texas.

Method

A nonexperimental, descriptive, correlational design was used for data collection. Participants (n = 192) completed a demographic survey, and marginality was measured using the Koci Marginality Index-70.

Results

There was a statistically significant difference in mean scores for a number of variables including gender, age, race/ethnicity, marital status, total household income, completion of a previous college degree, being a parent, and a student for whom English is a nonnative language.

Conclusion

The findings from this research study suggest that marginalization remains a significant issue for nontraditional, prelicensure nursing students.
Combinations of Bevacizumab With Immune Checkpoint Inhibitors in Renal Cell Carcinoma
Authors: Gao Xin , McDermott David F.
Published: August 2018

Renal cell carcinoma (RCC) is characterized by aberrant angiogenic signaling and an immunogenic tumor microenvironment. Systemic therapies targeting vascular endothelial growth factor and the immune checkpoints programmed cell death protein 1/programmed cell death protein 1 ligand and cytotoxic T-lymphocyte–associated protein 4 have advanced to the forefront of the treatment repertoire against advanced or metastatic RCC (mRCC). In preclinical models, inhibition of vascular endothelial growth factor signaling promotes antitumor immunity and may enhance the efficacy of immune checkpoint blockade. Bevacizumab, which has previously shown antitumor activity in mRCC as monotherapy and in combination with interferon α, is now under investigation in clinical trials in combinations involving multiple immune checkpoint inhibitors. The combination of bevacizumab plus atezolizumab has demonstrated efficacy in a randomized phase III study of treatment-naive mRCC patients whose tumors express programmed cell death protein 1 ligand. We review here the preclinical rationale for combining antiangiogenic therapies with immune checkpoint inhibitors and highlight the status of current clinical development of combinations involving bevacizumab and immune checkpoint inhibitors in RCC.
Bevacizumab in Cervical Cancer: 5 Years After
Authors: Pfaendler Krista S. , Liu Marisa C. , Tewari Krishnansu S.
Published: August 2018

Over the past 5 years, addition of bevacizumab to combination chemotherapy for advanced, recurrent, and persistent cervical cancer has offered prolonged overall and progression-free survival. Since the original press release announcing the survival benefits of this antiangiogenesis therapy, there has been further study of bevacizumab related to quality of life, combination with other agents, use of imaging to evaluate likelihood of response, and development of biosimilars. This review summarizes publications related to bevacizumab use in advanced, recurrent, and persistent cervical cancer over the past 5 years since initial proof of concept of antiangiogenesis therapy and the initial dissemination of information regarding survival benefits of bevacizumab.
Bevacizumab and Glioblastoma
Authors: Kim Michelle M. , Umemura Yoshie , Leung Denise
Published: August 2018

Glioblastoma (GBM) is the most common and lethal intracranial malignancy, with few advances in treatment over the last several decades. Much excitement surrounded the initial approval for bevacizumab for recurrent GBM, given the marked radiographic responses and improvement in progression-free survival observed in early studies. However, phase III studies have failed to demonstrate an overall survival advantage with the use of this agent. An overview of the mechanism of action and activity of bevacizumab in adult gliomas, a timeline of pivotal clinical trials, data on its impact on quality of life and imaging, and its role in managing the sequelae of treatment provide evidence for its current use. Investigations into combinatorial approaches utilizing bevacizumab with reirradiation and immunotherapy and ongoing work to identify biomarkers to select patient subsets who may benefit from treatment elucidate important unanswered questions that will further define the role of bevacizumab in the management of patients with GBM.
The Value of 16-cm Wide-Detector Computed Tomography in Coronary Computed Tomography Angiography for Patients With High Heart Rate Variability
Authors: Chen Yuhuan , Wei Donghong , Li Dou , Liu Zhentang , Hu Zhijun , Li Michelle , Jia Yongjun , Yu Yong , Han Dong , Ren Ranzhi , Yu Nan , He Taiping
Published: August 2018

Objective

The aim of this study was to investigate radiation dose and image quality of coronary computed tomography (CT) angiography (CCTA) for patients with high heart rate variability (HRv) using 16-cm wide-detector CT scanner.

Methods

One hundred sixty-six patients with uncontrolled heart rate underwent CCTA on a 16-cm wide-detector CT system and were divided into 2 groups based on their HRv for analysis: group A (n = 95, HRv ≤10 beats/min [bpm]) and group B (n = 71, HRv >10 bpm). Images in both groups were reconstructed with motion correction algorithm. Subjective and objective image qualities were analyzed.

Results

There were no significant differences in age, body mass index, and heart rate (68.1 ± 11.4 vs 67.6 ± 12.3 bpm) between the 2 groups (P > 0.05). However, group B had significantly higher HRv than group A (33.5 ± 24.4 vs 7.8 ± 1.2 bpm, P < 0.001). All images were acceptable for clinical diagnosis. Compared with group A, image quality scores in group B decreased slightly (4.1 ± 0.5 vs 4.0 ± 0.6). However, the difference was not statistically significant. The mean effective doses were both relatively low at 2.2 ± 1.1 mSv in group A and 2.6 ± 1.4 mSv in group B.

Conclusions

Single-heartbeat free-breathing CCTA can be performed for patients with high HRv using 16-cm wide-detector CT scanner to achieve diagnostic image quality with low radiation dose.
Transplantation of Human-induced Pluripotent Stem Cell-derived Cardiomyocytes Is Superior to Somatic Stem Cell Therapy for Restoring Cardiac Function and Oxygen Consumption in a Porcine Model of Myocardial Infarction
Authors: Ishida Masaru , Miyagawa Shigeru , Saito Atsuhiro , Fukushima Satsuki , Harada Akima , Ito Emiko , Ohashi Fumiya , Watabe Tadashi , Hatazawa Jun , Matsuura Katsuhisa , Sawa Yoshiki
Published: August 2018

Background

Somatic stem cell (SC) therapy can improve cardiac performance following ischemic injury. In this study, we investigated whether induced pluripotent SC-derived cardiomyocytes (iPS-CMs) are more effective than somatic SCs, such as skeletal myoblasts (SM) and mesenchymal (M)SCs, in promoting functional recovery upon transplantation in a porcine model of myocardial infarction.

Methods

Myocardial injury was induced by ameroid ring placement in immunosuppressed female mini pigs; after 1 month, epicardial cell transplantation was performed with iPS-CMs (n = 7), SMs (n = 7), and MSCs (n = 7). Control pigs underwent sham operation (n = 8).

Results

Cell therapy improved functional recovery 2 months after myocardial infarction, as evidenced by increased ejection fraction (iPS-CM, +7.3% ± 2.2% and SM, +5.8% ± 5.4% vs control, −4.4% ± 3.8%; P < 0.05). The analysis of regional contractile function in the infarcted zone revealed an increase in transverse peak strain (iPS-CM, +4.6% ± 2.2% vs control, −3.8% ± 4.7%; P < 0.05). The C-11 acetate kinetic analysis by positron emission tomography showed that the work-metabolic cardiac energy efficacy increased by the transplantation of iPS-CMs, but was reduced by the other cell types. This was accompanied by decreased myocardial wall stress in the infarcted zone (iPS-CM, −27.6 ± 32.3 Pa and SM, −12.8 ± 27 Pa vs control, +40.5 ± 33.9 Pa; P < 0.05).

Conclusions

The iPS-CM is superior to other somatic cell sources in terms of improving regional contractile function and cardiac bioenergetic efficiency, suggesting greater clinical benefits in severely damaged myocardium.
Assessing natural selection during range expansions: Insights from a spatially explicit ABC study
Authors: Kanitz Ricardo , Neuenschwander Samuel , Goudet Jérôme
Published: August 2018

For at least 40 years now, evolutionary biologists have discussed the relative roles of natural selection and genetic drift in shaping the genetic composition of populations. Range expansions are of particular interest in this discussion: They normally occur over environmental gradients allowing local adaptation to take place, but the demographic properties of these expansions also potentiate genetic-drift effects, which may in turn randomly generate extreme changes in allele frequencies as populations expand in territory and numbers (i.e. allele surfing). Here, we address the detection and measurement of selection in such scenario using simulations. We mimic a range expansion over a variable selective gradient where individuals have in their genomes both loci that are neutral and loci determining a quantitative trait subject to selection. The responsiveness of summary statistics to the selective pressure is then assessed, and estimates of the selective pressure are made – based on these statistics – with approximate Bayesian computation (ABC). We observe that statistics related to isolation-by-distance patterns present a strong response to selection. This response can be used in ABC to estimate the strength of selection acting on the simulated populations with very reliable measures of estimability, regardless of the genetic architecture underlying the selected trait. Furthermore, these estimates are robust to noise produced by other genetic and demographic parameters such as heritability, mutation, migration and population-growth rates. This approach of taking into account the spatial dimension of differentiation in quantitative traits offers a promising avenue of investigation about the role of natural selection in range-expansion scenarios, with possible implementations in the study of natural cases, as well.
Transcriptome and Comparative Genomics analyses reveal new functional insights on key determinants of pathogenesis and interbacterial competition inPectobacteriumandDickeyaspp
Authors: Bellieny-Rabelo Daniel , Tanui Collins K. , Miguel Nikki , Kwenda Stanford , Shyntum Divine Y. , Moleleki Lucy N.
Published: August 2018

Soft-rotEnterobacteriaceae(SRE) typified byPectobacteriumandDickeyagenera are phytopathogenic bacteria inflicting soft-rot disease in crops worldwide. By combining genomic information from 100 SRE with whole-transcriptome datasets, we identified novel genomic and transcriptional associations amongst key pathogenicity themes in this group. Comparative genomics revealed solid linkage between thetypeIsecretionsystem (T1SS) and the carotovoricin bacteriophage (Ctv) conserved in 96.7% ofPectobacteriumgenomes. Moreover, their co-activation during infection might indicate a novel functional association involving T1SS/Ctv. Another bacteriophage-borne genomic region mostly confined in less than 10% ofPectobacteriumorganisms was found, presumably comprising a novel lineage-specific prophage in the genus. We also detected the transcriptional co-regulation of a previously predicted toxin/immunity pair (WHH and SMI1_KNR4 families) along with type VI secretion system (T6SS) andhcp/vgrGgenes suggesting a role in disease development as T6SS-dependent effectors. Further, we showed that another predicted T6SS-dependent endonuclease (AHH-family) exhibited toxicity in ectopic expression assays indicating antibacterial activity. Additionally, we report the striking conservation of group-4-capsule (GFC) cluster in 100 SRE strains which consistently features adjacently conserved serotype-specific gene-arrays comprising a previously unknown organization in GFC clusters. Also, extensive sequence variations found ingfcAorthologs suggest a serotype-specific role in the GfcABCD machinery.
Induction of the BIMS Splice Variant Sensitizes Proliferating NK Cells to IL-15 Withdrawal
Authors: Jacobs Benedikt , Pfefferle Aline , Clement Dennis , Goodridge Jodie P. , Saetersmoen Michelle L. , Lorenz Susanne , Wiiger Merete Thune , Malmberg Karl-Johan
Published: August 2018

Adoptive transfer of allogeneic NK cells holds great promise for cancer immunotherapy. There is a variety of protocols to expand NK cells in vitro, most of which are based on stimulation with cytokines alone or in combination with feeder cells. Although IL-15 is essential for NK cell homeostasis in vivo, it is commonly used at supra-physiological levels to induce NK cell proliferation in vitro. As a result, adoptive transfer of such IL-15 addicted NK cells is associated with cellular stress due to sudden cytokine withdrawal. Here, we describe a dose-dependent addiction to IL-15 during in vitro expansion, leading to caspase-3 activation and profound cell death upon IL-15 withdrawal. NK cell addiction to IL-15 was tightly linked to the BCL-2/BIM ratio, which rapidly dropped during IL-15 withdrawal. Furthermore, we observed a proliferation-dependent induction of BIM short (BIM S), a highly pro-apoptotic splice variant of BIM, in IL-15 activated NK cells. These findings shed new light on the molecular mechanisms involved in NK cell apoptosis following cytokine withdrawal and may guide future NK cell priming strategies in a cell therapy setting.
A retrospective evaluation of automated optimization of deep brain stimulation parameters
Authors: Vorwerk Johannes , Brock Andrea A. , Anderson Daria N. , Rolston John D. , Butson Christopher R.
Published: August 2018

Objective

We performed a retrospective analysis of an optimization algorithm for the computation of patient-specific multipolar stimulation configurations employing multiple independent current/voltage sources. We evaluated whether the obtained stimulation configurations align with clinical data and whether the optimized stimulation configurations have the potential to lead to an equal or better stimulation of the target region as manual programming, while reducing the time required for programming sessions.

Methods

For three patients (five electrodes) diagnosed with essential tremor, we derived optimized multipolar stimulation configurations using an approach that is suitable for the application in clinical practice. To evaluate the automatically derived stimulation settings, we compared them to the results of the monopolar review.

Results

We observe a good agreement between the findings of the monopolar review and the optimized stimulation configurations, with the algorithm assigning the maximal voltage in the optimized multipolar pattern to the contact that was found to lead to the best therapeutic effect in the clinical monopolar review in all cases. Additionally, our simulation results predict that the optimized stimulation settings lead to the activation of an equal or larger volume fraction of the target compared to the manually determined settings in all cases.

Conclusions

Our results demonstrate the feasibility of an automatic determination of optimal DBS configurations and motivate a further evaluation of the applied optimization algorithm.
Structurally distinct endocytic pathways for B cell receptors in B lymphocytes
Authors: Roberts Aleah D. , Davenport Thaddeus M. , Dickey Andrea M. , Ahn Regina , Sochacki Kem A. , Taraska Justin W.
Published: August 2018

B lymphocytes play a critical role in adaptive immunity. Upon antigen binding, B cell receptors (BCR) cluster on the plasma membrane and are internalized by endocytosis. In this process, B cells capture diverse antigens in various contexts and concentrations. However, it is unclear whether the mechanism of BCR endocytosis changes in response to these factors. Here, we studied the mechanism of soluble antigen-induced BCR clustering and internalization in a cultured human B cell line using correlative super resolution fluorescence and platinum replica electron microscopy. First, by visualizing nanoscale BCR clusters, we provide direct evidence that BCR cluster size increases with F(ab’)2 concentration. Next, we show that the physical mechanism of internalization switches in response to BCR cluster size. At low concentrations of antigen, B cells internalize small BCR clusters by classical clathrin-mediated endocytosis. At high antigen concentrations, when clusters size increases beyond the size of a single clathrin coated pit, B cells retrieve receptor clusters using large invaginations of the plasma membrane capped with clathrin. At these sites, we observed early and sustained recruitment of actin and an actin polymerizing protein FCHSD2. We further show that actin recruitment is required for the efficient generation of these novel endocytic carriers and for their capture into the cytosol. We propose that in B cells, the mechanism of endocytosis switches to accommodate large receptor clusters formed when cells encounter high concentrations of soluble antigen. This mechanism is regulated by the organization and dynamics of the cortical actin cytoskeleton.
Penton-dodecahedron of fowl adenovirus serotype 4 as a vaccine candidate for the control of related diseases
Authors: Tang Qiuxia , Dangi Ruyi , Qiu Li , Yang Zengqi , Wang Xinglong
Published: August 2018

In some serotypes of adenovirus (Ad), the penton base protein and attached trimeric fiber assemble into dodecameric virus-like particles called penton-dodecahedron (Pt-Dd), which can internalize into cells and can be used to deliver the vaccine antigen and drugs. Fowl adenovirus serotype 4 (FAdV-4) is an important poultry pathogens and causing seriously economic lost to poultry industry in China and several other counties. The produce of Pt-Dd in FAdV-4 infected cells as well as in those infected with the recombinant human Ad expressing fiber-1, fiber-2, and penton base was determine by Transmission electron microscopy (TEM). For the First time, we proved that FAdV-4 produced Pt-Dd in infected cells, which can also be assembled by the overexpressed recombinant proteins fiber-1, fiber-2, and penton base. Pt-Dd, as well as the recombinant proteins fiber-1, fiber-2, and penton base, were then used to immunize chickens. The humoral immune response, cell mediate immune response (CMI), and challenge results were used to evaluate the immune efficacy of the vaccine candidates. Pt-Dd induced the highest level of enzyme-linked immunosorbent assay antibodies and high levels of CMI, showing a significantly (p < 0.05) high level of interferon γ, interleukin-4, and major histocompatibility complex II expressions in peripheral blood mononuclear cells at 48 h post-infection. The challenge results showed that Pt-Dd, inactivated FAdV-4 vaccine, as well as fiber-1 induced the best protection (100%), followed by fiber-2 (80%) and penton (67%). The present study showed that FAdV-4-Pt-Dd and recombinant fiber-1 are good FAdV-4 vaccine candidates and could be used to replace the tissue-sourced inactivated FAdV-4 vaccine.

Importance

FAdV-4-Pt-Dds were discovered in FAdV-4 infected cells, and which were also assembled in cells transduced with recombinant human adenovirus expressing fiber-1, fiber-2, and penton base. FAdV-4-Pt-Dds internalize into cells with high efficiency, so that it can be used for delivery vaccine antigen or drugs. Immunization chickens with Pt-Dd and fiber-1 obtained by transduction HEK-293T cells induced significant high level humoral and cellular mediated immune responses, and also 100% challenge protection in chickens indicating that they are good FAdV-4 vaccine candidates. What more, the Pt-Dd obtained by transduction HEK-293T cell would have no DNA and adenovirus contamination as adenovirus could not package in HEK-293T cells.