bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teaching for the recovery of meaning: An imagination‐centered pedagogical approach for today's college students
Authors: Manning Patrick R. 
Published: October 2017

AbstractIn the face of a mounting mental health crisis among college students, professors have an opportunity and responsibility to respond to their students’ psychological distress. Psychological and historical scholarship suggests that the proliferation of modern media and breakdown in traditional sources of existential meaning like religion are significant factors in young adults’ declining mental health. In response to this crisis, this article examines the crucial role of the imagination in constructing meaning and proposes an imagination‐centered pedagogical process by means of which teachers can assist students in recovering meaning and integration in their lives.
Conversation with 2016 American Academy of Religion Excellence in Teaching Award Winner Joanne Maguire Robinson
Authors: Robinson Joanne Maguire , Gallagher Eugene V. , Pui‐lan Kwok , Pearson Thomas 
Published: October 2017

AbstractThis conversation between the editors of Teaching Theology and Religion and Joanne Maguire Robinson continues an occasional series of interviews that has previously featured Jonathan Z. Smith, Stephen Prothero, Mary Pierce Brosmer, and Mary Elizabeth Mullino Moore. The exchange takes as its point of departure the teaching statement that Professor Robinson produced in support of her candidacy for the American Academy of Religion's Excellence in Teaching Award. Issues addressed include the impact of institutional context on one's teaching, teaching the humanities in universities that are ever more focused on job training, making the transition from a graduate program focused on research to teaching undergraduates who are unlikely to take even a second course in the study of religion, and ways in which women are challenged to navigate multiple responsibilities while striving to make their way in a male‐dominated academy.
Infective endocarditis in the setting of renal transplantation: Case report and review of the literature
Authors: Nardi Agmon Inbar , Goldberg Elad , Cohen Eytan , Krause Ilan 
Published: October 2017

AbstractThe potent immunosuppressive drugs used by transplant recipients place them at risk of infections. Data on infective endocarditis (IE) in the setting of renal transplantation (RT) are sparse. We describe a 36‐year‐old woman referred to a tertiary medical center for evaluation of elevated creatinine levels 1 month after a second RT. Work‐up revealed the presence of all four of Duke's criteria: fever, persistent bacteremia, new‐onset tricuspid regurgitation, and masses suspected to be vegetation attached to the tricuspid annulus. Symptoms resolved with antibiotic treatment and fluids. Fluorodeoxyglucose‐positron emission tomography/computed tomography (FDG‐PET/CT) revealed hypermetabolic absorption in the femoral vascular graft that had been used for hemodialysis prior to transplantation. The graft was removed by open surgery, and the patient was discharged home in good condition with continued antibiotic treatment. Review of the literature yielded 73 previously reported cases of IE in renal transplant recipients. Several differences were noted from IE in the general population: lower male predominance, younger age (<60 years), absence in most cases of a preexisting structural cardiac anomaly, and more variable causative pathogens. Our case also highlights the importance of FDG‐PET/CT for detecting the source of IE and alerts clinicians to the sometimes unexpected course of the disease in renal transplant recipients.
Atomic Structures of Minor Proteins VI and VII in Human Adenovirus
Authors: Dai Xinghong , Wu Lily , Sun Ren , Zhou Z. Hong 
Published: October 2017

ABSTRACT
Human adenoviruses (Ad) are double-stranded DNA (dsDNA) viruses associated with infectious diseases, but they are better known as tools for gene delivery and oncolytic anticancer therapy. Atomic structures of Ad provide the basis for the development of antivirals and for engineering efforts toward more effective applications. Since 2010, atomic models of human Ad5 have been derived independently from photographic film cryo-electron microscopy (cryo-EM) and X-ray crystallography studies, but discrepancies exist concerning the assignment of cement proteins IIIa, VIII, and IX. To clarify these discrepancies, we employed the technology of direct electron counting to obtain a cryo-EM structure of human Ad5 at 3.2-Å resolution. Our improved structure unambiguously confirms our previous cryo-EM models of proteins IIIa, VIII, and IX and explains the likely cause of conflict in the crystallography models. The improved structure also allows the identification of three new components in the cavity of hexon—the cleaved N terminus of precursor protein VI (pVIn), the cleaved N terminus of precursor protein VII (pVIIn2), and mature protein VI. The binding of pVIIn2—and, by extension, that of genome-condensing pVII—to hexons is consistent with the previously proposed dsDNA genome-capsid coassembly for adenoviruses, which resembles that of single-stranded RNA (ssRNA) viruses but differs from the well-established mechanism of pumping dsDNA into a preformed protein capsid exemplified by tailed bacteriophages and herpesviruses.

IMPORTANCE
Adenovirus is a double-edged sword to humans: it is a widespread pathogen but can be used as a bioengineering tool for anticancer and gene therapies. The atomic structure of the virus provides the basis for antiviral and application developments, but conflicting atomic models for the important cement proteins IIIa, VIII, and IX from conventional/film cryo-EM and X-ray crystallography studies have caused confusion. Using cutting-edge cryo-EM technology with electron counting, we improved the structure of human adenovirus type 5 and confirmed our previous models of cement proteins IIIa, VIII, and IX, thus clarifying the inconsistent structures. The improved structure also reveals atomic details of membrane-lytic protein VI and genome-condensing protein VII and supports the previously proposed genome-capsid coassembly mechanism for adenoviruses.
Human Metapneumovirus Induces Formation of Inclusion Bodies for Efficient Genome Replication and Transcription
Authors: Cifuentes-Muñoz Nicolás , Branttie Jean , Slaughter Kerri Beth , Dutch Rebecca Ellis 
Published: October 2017

ABSTRACT

Human metapneumovirus (HMPV) causes significant upper and lower respiratory disease in all age groups worldwide. The virus possesses a negative-sense single-stranded RNA genome of approximately 13.3 kb encapsidated by multiple copies of the nucleoprotein (N), giving rise to helical nucleocapsids. In addition, copies of the phosphoprotein (P) and the large RNA polymerase (L) decorate the viral nucleocapsids. After viral attachment, endocytosis, and fusion mediated by the viral glycoproteins, HMPV nucleocapsids are released into the cell cytoplasm. To visualize the subsequent steps of genome transcription and replication, a fluorescence
in situ
hybridization (FISH) protocol was established to detect different viral RNA subpopulations in infected cells. The FISH probes were specific for detection of HMPV positive-sense RNA (+RNA) and viral genomic RNA (vRNA). Time course analysis of human bronchial epithelial BEAS-2B cells infected with HMPV revealed the formation of inclusion bodies (IBs) from early times postinfection. HMPV IBs were shown to be cytoplasmic sites of active transcription and replication, with the translation of viral proteins being closely associated. Inclusion body formation was consistent with an actin-dependent coalescence of multiple early replicative sites. Time course quantitative reverse transcription-PCR analysis suggested that the coalescence of inclusion bodies is a strategy to efficiently replicate and transcribe the viral genome. These results provide a better understanding of the steps following HMPV entry and have important clinical implications.

IMPORTANCE
Human metapneumovirus (HMPV) is a recently discovered pathogen that affects human populations of all ages worldwide. Reinfections are common throughout life, but no vaccines or antiviral treatments are currently available. In this work, a spatiotemporal analysis of HMPV replication and transcription in bronchial epithelial cell-derived immortal cells was performed. HMPV was shown to induce the formation of large cytoplasmic granules, named inclusion bodies, for genome replication and transcription. Unlike other cytoplasmic structures, such as stress granules and processing bodies, inclusion bodies are exclusively present in infected cells and contain HMPV RNA and proteins to more efficiently transcribe and replicate the viral genome. Though inclusion body formation is nuanced, it corresponds to a more generalized strategy used by different viruses, including filoviruses and rhabdoviruses, for genome transcription and replication. Thus, an understanding of inclusion body formation is crucial for the discovery of innovative therapeutic targets.
Deletion of the African Swine Fever Virus Gene DP148R Does Not Reduce Virus Replication in Culture but Reduces Virus Virulence in Pigs and Induces High Levels of Protection against Challenge
Authors: Reis Ana L. , Goatley Lynnette C. , Jabbar Tamara , Sanchez-Cordon Pedro J. , Netherton Christopher L. , Chapman David A. G. , Dixon Linda K. 
Published: October 2017

ABSTRACT

Many of the approximately 165 proteins encoded by the African swine fever virus (ASFV) genome do not have significant similarity to known proteins and have not been studied experimentally. One such protein is DP148R. We showed that the DP148R gene is transcribed at early times postinfection. Deletion of this gene did not reduce virus replication in macrophages, showing that it is not essential for replication in these cells. However, deletion of this gene from a virulent isolate, Benin 97/1, producing the BeninΔDP148R virus, dramatically reduced the virulence of the virus
in vivo
. All pigs infected with the BeninΔDP148R virus survived infection, showing only transient mild clinical signs soon after immunization. Following challenge with the parental virulent virus, all pigs immunized by the intramuscular route (11/11) and all except one immunized by the intranasal route (5/6) survived. Mild or no clinical signs were observed after challenge. As expected, control nonimmune pigs developed signs of acute African swine fever (ASF). The virus genome and infectious virus were observed soon after immunization, coincident with the onset of clinical signs (∼10
6
genome copies or 50% tissue culture infective doses/ml). The levels of the virus genome declined over an extended period up to 60 days postimmunization. In contrast, infectious virus was no longer detectable by days 30 to 35. Gamma interferon (IFN-γ) was detected in serum between days 4 and 7 postimmunization, and IFN-γ-producing cells were detected in all pigs analyzed following stimulation of immune lymphocytes with whole virus. ASFV-specific antibodies were first detected from day 10 postimmunization.

IMPORTANCE
African swine fever (ASF) is endemic in Africa, parts of the Trans Caucasus, the Russian Federation, and several European countries. The lack of a vaccine hinders control. Many of the ASF virus genes lack similarity to known genes and have not been characterized. We have shown that one of these, DP148R, is transcribed early during virus replication in cells and can be deleted from the virus genome without reducing virus replication. The virus with the gene deletion, BeninΔDP148R, caused mild clinical signs in pigs and induced high levels of protection against challenge with the parental virulent virus. Therefore, deletion of this gene can provide a target for the rational development of vaccines.
Induction of DNA Damages upon Marek's Disease Virus Infection: Implication in Viral Replication and Pathogenesis
Authors: Bencherit Djihad , Remy Sylvie , Le Vern Yves , Vychodil Tereza , Bertzbach Luca D. , Kaufer Benedikt B. , Denesvre Caroline , Trapp-Fragnet Laëtitia 
Published: October 2017

ABSTRACTMarek's disease virus (MDV) is a highly contagious alphaherpesvirus that infects chickens and causes a deadly neoplastic disease. We previously demonstrated that MDV infection arrests cells in S phase and that the tegument protein VP22 plays a major role in this process. In addition, expression of VP22 induces double-strand breaks (DSBs) in the cellular DNA, suggesting that DNA damage and the associated cellular response might be favorable for the MDV life cycle. Here, we addressed the role of DNA damage in MDV replication and pathogenesis. We demonstrated that MDV induces DSBs during lytic infectionin vitroand in the peripheral blood mononuclear cells of infected animals. Intriguingly, we did not observe DNA damage in latently infected MDV-induced lymphoblastoid cells, while MDV reactivation resulted in the onset of DNA lesions, suggesting that DNA damage and/or the resulting DNA damage response might be required for efficient MDV replication and reactivation. In addition, reactivation was significantly enhanced by the induction of DNA damage using a number of chemicals. Finally, we used recombinant viruses to show that VP22 is required for the induction of DNA damagein vivoand that this likely contributes to viral oncogenesis.IMPORTANCEMarek's disease virus is an oncogenic alphaherpesvirus that causes fatal T-cell lymphomas in chickens. MDV causes substantial losses in the poultry industry and is also used in small-animal models for virus-induced tumor formation. DNA damage not only is implicated in tumor development but also aids in the life cycle of several viruses; however, its role in MDV replication, latency, and reactivation remains elusive. Here, we demonstrate that MDV induces DNA lesions during lytic replicationin vitroandin vivo. DNA damage was not observed in latently infected cells; however, it was reinitiated during reactivation. Reactivation was significantly enhanced by the induction of DNA damage. Recombinant viruses that lacked the ability to induce DNA damage were defective in their ability to induce tumors, suggesting that DNA damage might also contribute to cellular transformation processes leading to MDV lymphomagenesis.
Novel Selective Agents for the Degradation of Androgen Receptor Variants to Treat Castration-Resistant Prostate Cancer
Authors: Ponnusamy Suriyan , Coss Christopher C. , Thiyagarajan Thirumagal , Watts Kate , Hwang Dong-Jin , He Yali , Selth Luke A. , McEwan Iain J. , Duke Charles B. , Pagadala Jayaprakash , Singh Geetika , Wake Robert W. , Ledbetter Christopher , Tilley Wayne D. , Moldoveanu Tudor , Dalton James T. , Miller Duane D. , Narayanan Ramesh 
Published: October 2017

Abstract
Androgen receptor (AR) mediates the growth of prostate cancer throughout its course of development, including in abnormal splice variants (AR-SV)-driven advanced stage castration-resistant disease. AR stabilization by androgens makes it distinct from other steroid receptors, which are typically ubiquitinated and degraded by proteasomes after ligand binding. Thus, targeting AR in advanced prostate cancer requires the development of agents that can sustainably degrade variant isoforms for effective therapy. Here we report the discovery and characterization of potent selective AR degraders (SARD) that markedly reduce the activity of wild-type and splice variant isoforms of AR at submicromolar doses. Three SARDs (UT-69, UT-155, and (R)-UT-155) bind the amino-terminal transcriptional activation domain AF-1, which has not been targeted for degradation previously, with two of these SARD (UT-69 and UT-155) also binding the carboxy-terminal ligand binding domain. Despite different mechanisms of action, all three SARDs degraded wild-type AR and inhibited AR function, exhibiting greater inhibitory potency than the approved AR antagonists. Collectively, our results introduce a new candidate class of next-generation therapeutics to manage advanced prostate cancer. Cancer Res; 77(22); 6282–98. ©2017 AACR.
The Irreversible Covalent Fibroblast Growth Factor Receptor Inhibitor PRN1371 Exhibits Sustained Inhibition of FGFR after Drug Clearance
Authors: Venetsanakos Eleni , Brameld Ken A. , Phan Vernon T. , Verner Erik , Owens Timothy D. , Xing Yan , Tam Danny , LaStant Jacob , Leung Kwan , Karr Dane E. , Hill Ronald J. , Gerritsen Mary E. , Goldstein David M. , Funk Jens Oliver , Bradshaw J. Michael 
Published: October 2017

Abstract
An increasing number of cancers are known to harbor mutations, translocations, or amplifications in the fibroblast growth factor receptor (FGFR) family of kinases. The FGFR inhibitors evaluated in clinical trials to date have shown promise at treating these cancers. Here, we describe PRN1371, an irreversible covalent inhibitor of FGFR1-4 targeting a cysteine within the kinase active site. PRN1371 demonstrated strong FGFR potency and excellent kinome-wide selectivity in a number of biochemical and cellular assays, including in various cancer cell lines exhibiting FGFR alterations. Furthermore, PRN1371 maintained FGFR inhibition in vivo, not only when circulating drug levels were high but also after the drug had been cleared from circulation, indicating the possibility of sustained FGFR inhibition in the clinic without the need for continuous drug exposure. Durable tumor regression was also obtained in multiple tumor xenografts and patient-derived tumor xenograft models and was sustained even using an intermittent dosing strategy that provided drug holidays. PRN1371 is currently under clinical investigation for treatment of patients with solid tumors. Mol Cancer Ther; 16(12); 2668–76. ©2017 AACR.
Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma
Authors: Pectasides Eirini , Stachler Matthew D. , Derks Sarah , Liu Yang , Maron Steven , Islam Mirazul , Alpert Lindsay , Kwak Heewon , Kindler Hedy , Polite Blase , Sharma Manish R. , Allen Kenisha , O'Day Emily , Lomnicki Samantha , Maranto Melissa , Kanteti Rajani , Fitzpatrick Carrie , Weber Christopher , Setia Namrata , Xiao Shu-Yuan , Hart John , Nagy Rebecca J. , Kim Kyoung-Mee , Choi Min-Gew , Min Byung-Hoon , Nason Katie S. , O'Keefe Lea , Watanabe Masayuki , Baba Hideo , Lanman Rick , Agoston Agoston T. , Oh David J. , Dunford Andrew , Thorner Aaron R. , Ducar Matthew D. , Wollison Bruce M. , Coleman Haley A. , Ji Yuan , Posner Mitchell C. , Roggin Kevin , Turaga Kiran , Chang Paul , Hogarth Kyle , Siddiqui Uzma , Gelrud Andres , Ha Gavin , Freeman Samuel S. , Rhoades Justin , Reed Sarah , Gydush Greg , Rotem Denisse , Davison Jon , Imamura Yu , Adalsteinsson Viktor , Lee Jeeyun , Bass Adam J. , Catenacci Daniel V. 
Published: October 2017

Abstract
Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited efficacy. A potential reason for the failure of such therapies is that genomic profiling results could commonly differ between the primary and metastatic tumors. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, finding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations. Multiregion sequencing showed significant discrepancy within the primary tumor (PT) and between the PT and disseminated disease, with oncogene amplification profiles commonly discordant. In addition, a pilot analysis of cell-free DNA (cfDNA) sequencing demonstrated the feasibility of detecting genomic amplifications not detected in PT sampling. Lastly, we profiled paired primary tumors, metastatic tumors, and cfDNA from patients enrolled in the personalized antibodies for GEA (PANGEA) trial of targeted therapies in GEA and found that genomic biomarkers were recurrently discrepant between the PT and untreated metastases. Divergent primary and metastatic tissue profiling led to treatment reassignment in 32% (9/28) of patients. In discordant primary and metastatic lesions, we found 87.5% concordance for targetable alterations in metastatic tissue and cfDNA, suggesting the potential for cfDNA profiling to enhance selection of therapy.
Significance: We demonstrate frequent baseline heterogeneity in targetable genomic alterations in GEA, indicating that current tissue sampling practices for biomarker testing do not effectively guide precision medicine in this disease and that routine profiling of metastatic lesions and/or cfDNA should be systematically evaluated. Cancer Discov; 8(1); 37–48. ©2017 AACR.
See related commentary by Sundar and Tan, p. 14.
See related article by Janjigian et al., p. 49.
This article is highlighted in the In This Issue feature, p. 1
Performance Evaluation of GaN based Thin Film Transistor using TCAD Simulation
Authors: Dargar Shashi Kant , Srivastava J K , Bharti Santosh , Nyati Abha 
Published: October 2017

<p>As reported in past decades, gallium nitride as one of the most capable compound semiconductor, GaN-based high-electron mobility transistors are the focus of intense research activities in the area of high power, high-speed, and high-temperature transistors. In this paper we present a design and simulation of the GaN based thin film transistor using sentaurus TCAD for the extracting the electrical performance. The resulting GaN TFTs exhibits good electrical performance in the simulated results, including, a threshold voltage of 12-15 V, an on/off current ratio of 6.5×10<sup>7 </sup>~8.3×10<sup>8</sup>, and a sub-threshold slope of 0.44V/dec. Sentaurus TCAD simulations is the tool which offers study of comprehensive behavior of semiconductor structures with ease. The simulation results of the TFT structure based on gallium nitride active channel have great prospective in the next-generation flat-panel display applications.</p>
A Utilisation of Improved Gabor Transform for Harmonic Signals Detection and Classification Analysis
Authors: Jopri M.H. , Abdullah A.R. , Sutikno T. , Manap M. , Yusoff M.R. 
Published: October 2017

This paper presents a utilization of improved Gabor transform for harmonic signals detection and classification analysis in power distribution system. The Gabor transform is one of time frequency distribution technique with a capability of representing signals in jointly time-frequency domain and known as time frequency representation (TFR). The estimation of spectral information can be obtained from TFR in order to identify the characteristics of the signals. The detection and classification of harmonic signals for 100 unique signals with numerous characteristic of harmonics with support of rule-based classifier and threshold setting that been referred to IEEE standard 1159 2009. The accuracy of proposed method is determined by using MAPE and the outcome demonstrate that the method gives high accuracy of harmonic signals classification. Additionally, Gabor transform also gives 100 percent correct classification of harmonic signals. It is verified that the proposed method is accurate and cost efficient in detecting and classifying harmonic signals in distribution system.
5G Fixed Beam Switching on Microstrip Patch Antenna
Authors: Ching Yu Low , Kamarudin Muhammad Ramlee 
Published: October 2017

<span lang="EN-US">5G technology is using millimeter-wave band to improve the wireless communication system. However, narrow transmitter and receiver beams have caused the beam coverage area to be limited. Due to propagation limitations of mm wave band, beam forming technology with multi-beam based communication system, has been focused to overcome the problem. In this letter, a fixed beam switching method is introduced. By changing the switches, four different configurations of patch array antennas are designed to investigate their performances in terms of radiation patterns, beam forming angle, gain, half-power bandwidth and impedance bandwidth at 28 GHz operating frequency for 5G application. Mircostrip antenna is preferred due to its low profile, easy in feeding and array configurations. Three different beam directions had been formed at -15°, 0°, and 15° with half-power bandwidth of range 45˚ to 50˚.</span>