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In collaboration with the American College of Veterinary Pathologists

Architecture now is unthinkable without images. This is not only owing to the pervasive representation of buildings through photographs, renderings, or some hybrid of both. Perhaps more critically,...

The use of DNA barcoding has revolutionized biodiversity science, but its application depends on the existence of comprehensive and reliable reference libraries. For many poorly known taxa, such reference sequences are missing even at higher-level taxonomic scales. We harvested the collections of the Smithsonian’s National Museum of Natural History (USNM) to generate DNA barcoding sequences for genera of terrestrial arthropods previously not recorded in one or more major public sequence databases. Our workflow used a mix of Sanger and Next-Generation Sequencing (NGS) approaches to maximize sequence recovery while ensuring affordable cost. In total, COI sequences were obtained for 5,686 specimens belonging to 3,888 genera and 202 families. Success rates varied widely according to collection data and focal taxon. NGS helped recover sequences of specimens that failed a previous run of Sanger sequencing. Success rates and the optimal balance between Sanger and NGS are the most important drivers to maximize output and minimize cost in future projects. The corresponding sequence and taxonomic data can be accessed through the Barcode of Life Data System, GenBank, the Global Biodiversity Information Facility, the Global Genome Biodiversity Network Data Portal and the NMNH data portal.

Publisher Copyright: © 2021 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd. To associate specimens identified by molecular characters to other biological knowledge, we need reference sequences annotated by Linnaean taxonomy. In this study, we (1) report the creation of a comprehensive reference library of DNA barcodes for the arthropods of an entire country (Finland), (2) publish this library, and (3) deliver a new identification tool for insects and spiders, as based on this resource. The reference library contains mtDNA COI barcodes for 11,275 (43%) of 26,437 arthropod species known from Finland, including 10,811 (45%) of 23,956 insect species. To quantify the improvement in identification accuracy enabled by the current reference library, we ran 1000 Finnish insect and spider species through the Barcode of Life Data system (BOLD) identification engine. Of these, 91% were correctly assigned to a unique species when compared to the new reference library alone, 85% were correctly identified when compared to BOLD with the new material included, and 75% with the new material excluded. To capitalize on this resource, we used the new reference material to train a probabilistic taxonomic assignment tool, FinPROTAX, scoring high success. For the full-length barcode region, the accuracy of taxonomic assignments at the level of classes, orders, families, subfamilies, tribes, genera, and species reached 99.9%, 99.9%, 99.8%, 99.7%, 99.4%, 96.8%, and 88.5%, respectively. The FinBOL arthropod reference library and FinPROTAX are available through the Finnish Biodiversity Information Facility (www.laji.fi) at https://laji.fi/en/theme/protax. Overall, the FinBOL investment represents a massive capacity-transfer from the taxonomic community of Finland to all sectors of society.

This paper examines the writing of Irish national character in terms of various contemporary and contested modes of constructing masculinity in Sydney Owenson’s O’Donnel (1814) and Maria Edgeworth’s Ormond (1817). Antiquarian, chivalric, modern, cosmopolitan, reasoned, sentimental, and romanticist vectors of masculinity are examined as ideological constructions fundamentally related to various generic and formal structures deployed in each novel. The article argues ultimately that the relative invisibility of O’Donnel in the canon of the English-language novel is related to its construction of a particular type of masculinity embedded in a pointed and conscious generic promiscuity. By contrast, Edgeworth’s reception is related from the outset to both her construction of a unified realism and a very particular masculine national type, as Englishness. In conclusion, the article notes an instance of contemporary (1816) concern with working-class feminine readership as evidence of an understanding that the politics of gender and representation in the novel have real-world social effects.

Inhibition of glutaminase-1 (GLS-1) hampers the proliferation of tumor cells reliant on glutamine. Known glutaminase inhibitors have potential limitations, and in vivo exposures are potentially limited due to poor physicochemical properties. We initiated a GLS-1 inhibitor discovery program focused on optimizing physicochemical and pharmacokinetic properties, and have developed a new selective inhibitor, compound 27 (IPN60090), which is currently in phase 1 clinical trials. Compound 27 attains high oral exposures in preclinical species, with strong in vivo target engagement, and should robustly inhibit glutaminase in humans.

Background The optimal method of labor induction is not known. It is important to determine the safest and efficient method to minimize the length of labor, hospital stay, cost, and adverse outcomes. Objective This study aims to determine if induction of labor with simultaneous use of oxytocin and Foley balloon versus the sequential use of Foley balloon followed by oxytocin decreases the time to delivery in multiparous women. Study Design We conducted a randomized controlled trial of multiparous women who presented for induction of labor at Mount Sinai from December 2013 to April 2016. Patients were admitted for induction with indications determined by their provider. Women with a nonanomalous, singleton fetus ≥ 24 weeks in vertex presentation with intact membranes were offered participation. Exclusion criteria included the history of uterine surgery, unexplained vaginal bleeding, latex allergy, or contraindication to vaginal delivery. Participants were randomized to either simultaneous (oxytocin and Foley balloon) or sequential (oxytocin after the expulsion of Foley balloon) induction group. The primary outcome was the time from induction to delivery. Secondary outcomes included mode of delivery, estimated blood loss (EBL), postpartum hemorrhage (PPH), chorioamnionitis, and composite neonatal outcome. Maternal and neonatal outcomes were collected via chart review. Analyses were done on an intention-to-treat basis. Results A total of 142 patients were enrolled; 75 in the simultaneous and 67 in the sequential group. There were no differences in baseline characteristics in the two groups. There was no difference in median time to delivery between groups (10.7 vs. 10.6 hours, p = 0.44). There was no difference in the rate of cesarean delivery, EBL, PPH, chorioamnionitis, or composite neonatal outcome. Conclusion Simultaneous use of oxytocin and Foley balloon for induction of labor does not decrease time to delivery in multiparas.

REVIEW QUESTION/OBJECTIVE The objective of the systematic review is to synthesize the best available evidence on the effectiveness of thoracic paravertebral block compared with the use of systemic analgesia on postoperative pain in patients who have undergone a thoracotomy procedure.

The characterization of polyubiquitin chains has been an analytical challenge for several decades. It has been shown that anchored and unanchored polyubiquitin chains with different isopeptide linkages and lengths exhibit a wide range of profoundly different cellular functions. However, structure function studies have been hindered by the difficulty of characterizing these complex chain structures. This report presents a broadly applicable workflow to characterize ubiquitin tetramers without the need for genetic mutations or reiterative immunoprecipitations. We use a top-down proteomic strategy that exploits ETciD activation on an orbitrap Fusion Lumos and manual interpretation aided by graphical interpretation of mass shifts to facilitate characterization of chain topography and lysine linkage sites. Our workflow differentiates all topological features of the numerous isomers of tetraubiquitin, which have molecular masses in excess of 34 000 Da and identifies linkage sites in these branched proteins. Copyright © 2016 John Wiley & Sons, Ltd.

Preterm premature rupture of the membranes (PPROM) is spontaneous rupture of membranes before 37 weeks' gestation before the onset of labor. The standard of care is inpatient management with antibiotics and monitoring. Bed rest has not been shown to be beneficial in the setting of PPROM and has adverse maternal effects. We conducted a pilot randomized clinical trial (RCT) to determine the feasibility of recruitment for an RCT of this nature and obtain estimates of the frequency of maternal and neonatal outcomes.Patients who were diagnosed with PPROM 34 weeks gestational age were randomized to bed rest versus activity in a 1:1 ratio. Subjects in both groups wore pedometers and kept activity logs. Maternal demographic and obstetric data and neonatal outcomes were collected and compared between groups using chi-square and Fisher exact tests. Latency was evaluated with log-rank test and Kaplan-Meier analysis.In this study, 36 women were enrolled and randomized; 1 patient withdrew. Complete data were available for 21 subjects. In univariable analysis, women in the activity group had a nonsignificantly shorter latency time than the bed rest group (median 6.0 vs. 8.5 days). Neonatal outcomes were similar between groups. Using log-rank sum analysis, neonates born to mothers in the activity group were more likely to develop necrotizing enterocolitis (NEC) than in the control group (24 vs. 0%, p = 0.05); this difference was not significant after false discovery rate correction (p = 0.80).This is the first randomized controlled study to evaluate bed rest versus normal activity in the setting of PPROM 34 weeks. This study demonstrates a nonsignificant increase in latency to delivery on bed rest and possible increase in NEC in the activity group; the mechanism remains unclear. We would recommend a larger RCT to better clarify these findings.

To provide passive heat storage in buildings, materials exhibiting a phase-change within building operating temperature can be incorporated into the envelope material. This study assesses the viability of incorporating a paraffin phase change material (PCM) into an Engineered Cementitious Composite (ECC) because the tensile ductility of ECC allows formation of thin panels—a favorable geometry for building facades. Inclusion of 3% PCM by mass provided a 40% increase in ECC specific heat capacity at phase change temperature while maintaining a 28 MPa compressive strength and 4% tensile strain capacity on average.

With limited therapeutic options, poor overall 5-year survival rates, and increasing incidence, pancreas cancer is estimated to become the second leading cause of cancer deaths by 2030. Recognizing the need for transformative advances in pancreas cancer management, we developed an in vivo target discovery platform to uncover molecular vulnerabilities in patient-derived pancreatic ductal adenocarcinoma (PDAC) xenografts to identify and rapidly translate novel therapeutic concepts to the clinic. We identified protein arginine methyltransferase 1 (PRMT1) as a dependency in PDAC required for disease maintenance and progression. Extensive genetic and pharmacological studies support PRMT1 as a novel vulnerability, which prompted our design and synthesis of proprietary series of potent, selective PRMT Type I inhibitors (PRMTi) with compelling in vivo activity. While advancing the project in drug discovery, we deployed a comprehensive approach to elucidate the mechanism of action of PRMTi. We characterized the PRMT1 interactome via PRMT1 immunoprecipitation followed by LC/MS and observed that PRMT1 binding partners were significantly enriched in RNA-binding and -processing genes. In addition, because methylation of arginine residues is a common post-translational modification regulating protein function, we identified substrates differentially methylated upon PRMT inhibition. Integrating these results with the PRMT1 interactome confirmed a strong correlation between PRMT1 substrates and complexes that are physically associated and linked to RNA metabolism. Transcriptome assays demonstrated that PRMT inhibition globally impaired RNA metabolism, including but not limited to RNA splicing, transcription termination, and R-loop formation. In addition, PRMTi caused a profound down-regulation of multiple pathways involved in the DNA damage response (DDR) promoting genomic instability. Taken together, these data support PRMT1 as a compelling target in an area of high unmet medical need and inform a mechanism-based translational strategy for future clinical development. Citation Format: Virginia Giuliani, Alessandro Carugo, Meredith Miller, Lionel Sanz, Chiu-Yi Liu, Christopher A Bristow, Erika Suzuki, Caleb A Class, Stella R. Hartono, Guang Gao, Ningping Feng, Jason P Gay, Bhavatarini Vangamudi, Joseph R Marszalek, Jeffrey Kovacs, Maria Emilia Di Francesco, Frederic Chedin, Philip Jones, Giulio Draetta, Timothy Heffernan. Inhibition of protein arginine methylation alters RNA metabolism and DNA damage response providing a new therapeutic strategy in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 277.

The characterization of polyubiquitin chains has been an analytical challenge for several decades. It has been shown that anchored and unanchored polyubiquitin chains with different isopeptide linkages and lengths exhibit a wide range of profoundly different cellular functions. However, structure function studies have been hindered by the difficulty of characterizing these complex chain structures. This report presents a broadly applicable workflow to characterize ubiquitin tetramers without the need for genetic mutations or reiterative immunoprecipitations. We use a top-down proteomic strategy that exploits ETciD activation on an orbitrap Fusion Lumos and manual interpretation aided by graphical interpretation of mass shifts to facilitate characterization of chain topography and lysine linkage sites. Our workflow differentiates all topological features of the numerous isomers of tetraubiquitin, which have molecular masses in excess of 34 000 Da and identifies linkage sites in these branched proteins. Copyright © 2016 John WileySons, Ltd.

Background Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and interchange of hospital-associated strains carrying the staphylococcal chromosomal cassette mec -II (SCC mec -II) with those in the community (SCC mec -IV) has increased. This study assesses the impact of MRSA and different MRSA types on clinical outcomes, medication use, and antibiotic sensitivities. Methods MRSA isolates from CF patients at our center were typed by SCC mec - and pv l status. Patient characteristics, lung function and nutrition are compared between MRSA types and to age, gender and Pseudomonas aeruginosa matched patients with chronic methicillin sensitive S. aureus (MSSA) infection. Results Seventy-two percent of patients carry pv l negative SCC mec -II isolates. Seventeen percent of all MRSA were SCC mec -IV pv l positive (USA300). These patients were younger and fewer had chronic P. aeruginosa infection, whereas pv l -negative SCC mec -IV isolates show highest antibiotic resistance. Nutritional outcomes and FEV1 percent predicted (75.1±2.7 versus 77.9±2.7) did not differ in patients with MRSA compared to those with MSSA but MRSA patients received more pulmonary maintenance but not oral antibiotic medications. Conclusion Patients with chronic MRSA are treated more intensely than age, gender and Pseudomonas aeruginosa matched MSSA-positive patients but clinical characteristics within MRSA patients vary depending on MRSA types.

Housework seemed an interminable chore to her. She had never liked it, any more than she liked cooking. But she had always done what was necessary. Now even that oppressed her to such an extent that she would often let things go until the last moment, sometimes failing to make up the beds until just before Charlie got home, and letting days, weeks, go by without dusting and vacuuming. The worse the house got the harder it was for her to do anything about it. She wanted to shut her eyes and forget it. See Horowitz's thorough reading of the papers that document the evolution of Friedan's political and theoretical understanding, housed at the Schlesinger Library, Radcliffe College, Cambridge, MA. And all the time, every day, at every hour and in every imaginable posture she dreamed of Laura. She dreamed of the romance, unfettered with family obligation or dish washing, free of the daily drudgery she so despised. … (Bannon 1960 ).

Tetrathiomolybdate (TM) is a potent nontoxic orally delivered copper complexing agent under development for the last several years for the treatment of Wilson's disease. It has been shown to block angiogenesis in primary and metastatic tumors. Therefore, the combination of cytotoxic radiotherapy (RT) and antiangiogenic TM could target both the existing tumor and the tumor microvasculature in a comprehensive strategy. Using a Lewis lung high metastatic (LLHM) carcinoma mouse tumor model, we demonstrate that the combination of TM and RT is more effective than either used as monotherapy. We also show that their therapeutic effects are additive, with no additional toxicity. We show that TM has no significant cytotoxicity in vitro against LLHM tumor cells, further supporting the antiangiogenic mechanism for its action.

Objective The goal was to determine the safety and efficacy of absolute ethyl alcohol treatment in the management of intra-axial brain arteriovenous malformations (AVMs). Methods Seventeen patients (eight female and nine male patients; mean age, 41 yr) underwent ethanol endovascular therapy for treatment of their brain AVMs. Superselective amytal testing preceded all procedures. Neuroleptic intravenous anesthesia was used for 16 patients, and general anesthesia was used for 1 patient. Follow-up monitoring consisted of clinical evaluations, magnetic resonance imaging, and arteriography. Results In follow-up evaluations (mean follow-up period, 13 mo) after embolization of brain AVMs, neither vascular recanalization nor the neovascular recruitment phenomenon was observed in any patient. Progressive AVM thrombosis at arteriographic follow-up evaluation was a constant feature. Seven patients were cured of their AVMs with ethanol endovascular therapy alone. Three patients were cured of their lesions with ethanol embolization plus surgical resection. One patient was cured of his lesion with ethanol embolization and radiation therapy of the residual nidus. Three patients underwent only partial therapy, with significant improvement in symptoms. Three patients are currently undergoing ethanol endovascular therapy. Complications occurred with 8 of 17 patients, most of which were transient. Two patients died because of late subarachnoid hemorrhages, one patient 4 months and one patient 14 months after partial therapy. Conclusion Progressive and permanent AVM occlusion is a common finding in arteriographic follow-up evaluations. In no patients did arterial recanalization or the neovascular recruitment phenomenon occur. Our initial results indicate that ethanol has a permanence that is seldom encountered with other embolic agents. With aggressive decadron therapy, the complications related to swelling in the brain are largely reversible.

This paper examines knowledge, risk perception, and attitudes around the H1N1 pandemic among Latino hard-to-reach (HTR) populations in the United States. Ten focus groups were conducted throughout California (N=90), representing Latino immigrants disproportionately affected by H1N1: farmworkers, indigenous Mexicans, pregnant women, and children. Overall, participants were aware of the H1N1 epidemic and common prevention practices. However, many expressed doubts that the H1N1 outbreak constituted an epidemic because the U.S. media reports of the epidemic in Mexico did not match reports from participants' families in Mexico and because of participants' absence of personal experience with the disease. Participants mistrusted the H1N1 vaccine due to its novelty, conspiracy theories, and inconsistent information. Study findings confirm that vaccination campaign strategies should reflect the diversity of meaning, experiences, and socio-economic realities among target populations. Key findings inform future emergency response activities targeting HTR Latino communities.

The conclusion to Gissing’s A Life’s Morning describes romantic plenitude in terms which almost make its opposite, which gesture toward emptiness and loss. Emily’s physical touch is only a layer of signification for Wilfred Athel. It is ‘the symbol of’ fulfilled desire. She is the feminine object of a desire written as aesthetic, within an impossible relation of class economics. This novel, written in 1885, was serialised in the Cornhill in 1888, after the publications of Thyrza and Demos. It follows a pattern common to the 1880s and 1890s, being both romance and socialist critique. It also expresses a preoccupation with the relation between aesthetics and gender which continues through Eve’s Ransom and The Crown of Life—novels structured around a complex dynamic involving economic agency, ‘artistic’ yearnings and sexual desire. These three works sit uneasily atop a widely accepted critical division of Gissing’s oeuvre into socialist and ‘new woman’ fictions, or into naturalist and psychological novels. The structuring experience of gendered desire forms a link between these poles which can illuminate the problematic divisions between them. Each of these works produces a relation between gendered object-relation, aesthetics and capital which defines a very particular structure of feeling, regardless of any critical division which might be used to separate them.

Joyce’s ‘The Dead’ enacts its ironic failure through Gabriel Conroy’s aesthetic and sexual relation to his wife, Gretta. From Gabriel’s focalising distance she is first read as art, then as the object of his sexual desire, then finally, in the story’s moment of failure, through her own puzzling interiority. The question ‘what is a woman standing on the stairs in the shadow, listening to distant music, a symbol of’ is interrupted by Gretta Conroy’s sudden and troubling subjectivity: Gabriel watched his wife who did not join the conversation. She was standing right under the dusty fanlight and the flame of the gas lit up the rich bronze of her hair which he had seen her drying at the fire a few days before. She was in the same attitude and seemed unaware of the talk about her. At last she turned towards them and Gabriel saw there was colour on her cheeks and that her eyes were shining. A sudden tide of joy went leaping out of his heart. (Joyce, 1914, p. 263)