bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sweet sensing, homeostasis and hedonics in the human gut–brain axis
Authors: Stamataki N. S. , McLaughlin J. T. 
Published: May 2017

AbstractConsumption of added sugars has been associated with excessive energy intake, obesity and its comorbidities, while non‐nutritive sweeteners offer caloric‐free sweet taste and might be helpful in decreasing energy intake. The importance of gut–brain nutrient signalling in the regulation of food intake has recently become a field of extensive research; however, understanding about how nutritive and non‐nutritive sweet tastants affect gut–brain crosstalk is limited. Much of the research has focused on the effects of non‐nutritive sweeteners on gut function, especially after the demonstration that sweet taste receptors are also present in enteroendocrine cells. However, the majority of human studies have not confirmed a physiologically significant biological activity of non‐nutritive sweeteners, nor a role for gut sweet taste receptors in glucose and gut peptide postprandial responses, gastric emptying or appetite. The use of functional and physiological MRI scanning has enabled the investigation of human brain responses to sweet tastants. Imaging studies have demonstrated that the human brain is able to distinguish the sweet taste of caloric sugars from non‐nutritive sweeteners, most likely as a result of nutrient detection in the gut. More studies are required to explore the comparative effects of caloric sugars and non‐nutritive sweeteners on homeostatic, neurophysiological and hedonic signals, which may interact to determine the effects of sweet sensing.
Computational Investigations of Multiword Chunks in Language Learning
Authors: McCauley Stewart M. , Christiansen Morten H. 
Published: May 2017

AbstractSecond‐language learners rarely arrive at native proficiency in a number of linguistic domains, including morphological and syntactic processing. Previous approaches to understanding the different outcomes of first‐ versus second‐language learning have focused on cognitive and neural factors. In contrast, we explore the possibility that children and adults may rely on different linguistic units throughout the course of language learning, with specific focus on the granularity of those units. Following recent psycholinguistic evidence for the role of multiword chunks in online language processing, we explore the hypothesis that children rely more heavily on multiword units in language learning than do adults learning a second language. To this end, we take an initial step toward using large‐scale, corpus‐based computational modeling as a tool for exploring the granularity of speakers' linguistic units. Employing a computational model of language learning, the Chunk‐Based Learner, we compare the usefulness of chunk‐based knowledge in accounting for the speech of second‐language learners versus children and adults speaking their first language. Our findings suggest that while multiword units are likely to play a role in second‐language learning, adults may learn less useful chunks, rely on them to a lesser extent, and arrive at them through different means than children learning a first language.
Analogy Lays the Foundation for Two Crucial Aspects of Symbolic Development: Intention and Correspondence
Authors: Yuan Lei , Uttal David H. 
Published: May 2017

AbstractWe argue that analogical reasoning, particularly Gentner's (1983, 2010) structure‐mapping theory, provides an integrative theoretical framework through which we can better understand the development of symbol use. Analogical reasoning can contribute both to the understanding of others’ intentions and the establishment of correspondences between symbols and their referents, two crucial components of symbolic understanding. We review relevant research on the development of symbolic representations, intentionality, comparison, and similarity, and demonstrate how structure‐mapping theory can shed light on several ostensibly disparate findings in the literature. Focusing on visual symbols (e.g., scale models, photographs, and maps), we argue that analogy underlies and supports the understanding of both intention and correspondence, which may enter into a reciprocal bootstrapping process that leads children to gain the prodigious human capacity of symbol use.
Comparison of laparoscopic‐assisted technique and open laparotomy for gastrointestinal biopsy in cats*
Authors: McClaran Janet Kovak , Skerrett Suzanne C. , Currao Rachael L. , Pavia Philippa R. , Tarvin Kiki M. 
Published: May 2017

AbstractObjectiveTo evaluate and compare the complications, postoperative pain, surgical time, hospitalization time, and adequacy of biopsy specimens between laparoscopic assisted (LAP) versus open laparotomy (OPEN) gastrointestinal biopsies in cats.Study DesignProspective randomized clinical study.Sample PopulationTwenty‐eight cats with clinical and ultrasonographic evidence of gastrointestinal disease. Fifteen cats in the LAP group and 13 in the OPEN group.MethodsSignalment, presenting clinical signs, total duration of surgery, operative time, ease of procedure, incision length, postoperative pain scores, complications, and duration of hospitalization were recorded. Quality of gastrointestinal biopsies was compared between techniques.ResultsThere was no difference in frequency of intraoperative complications (P = .778), surgical duration (P = .333), postoperative complications (P = .722), or duration of hospitalization (P = .728). Pain scores assigned before (P = .198) or 1 hour after surgery (P = .073) did not differ between groups; however, pain scores were lower at 6 hours (P = .003), 12 hours (P = .001), and 24 hours (P = .005) postoperatively in the LAP group. All cases survived surgery, with one case requiring conversion, and diagnostic biopsies were obtained in all cases.ConclusionLaparoscopic‐assisted gastrointestinal biopsy technique provided diagnostic specimens and decreased postoperative pain compared to open surgical techniques. No difference was detected in surgical duration, complications, or duration of hospitalization.
A computational study of the main degradation product of antitumor drug imexon
Authors: Kheffache Djaffar , Ouamerali Ourida 
Published: May 2017

We theoretically study, from the thermodynamic point of view, the possibility of the two degradation pathways of antitumor drug of imexon. According to the theoretical results obtained at DFT level in both gas and aqueous phases, the two degradation pathways of imexon are characterized by negative reaction Gibbs free energies. It has been found that 4-imino-5-methylene-imidazolidin-2-one is the favored degradation product of imexon. Herein, the focus of this work has been on calculating the geometries, relative energies and electronic properties of all possible prototropic tautomers of 4-imino-5-methylene-imidazolidin-2-one using the DFT and MP2 levels. The bulk water environment has been simulated by continuum model using Solvation Model based on Density (SMD). The UV spectra of two dominant tautomers of 4-imino-5-methylene-imidazolidin-2-one are also predicted using time-dependent density functional theory and the results are compared with the available experimental data. The comparison of the simulated and the experimental absorption spectra has allowed us to accurately characterize the predominant tautomer of the degradation product in aqueous medium.
Designing online writing classes to promote multimodal literacies
Authors: Bourelle Tiffany , Clark-Oates Angela , Bourelle Andrew 
Published: May 2017

In this entry, we argue that to promote multimodal literacy in online writing classes, instructors should address the following five practices in their course design:• Incorporate multimodal assignments and appropriate scaffolding tools;• Use multimodal instructional tools to teach and model multimodal composition;• Provide multimodal feedback to students' compositions;• "Teach" technology through the use of media labs;• Encourage reflection as a significant part of students' learning process.In so doing, we discuss each practice in depth, addressing the reasons and benefits for incorporating each, as well as advice about how to implement them. By implementing these practices in their online courses, instructors can successfully design classes that promote multimodal literacy.
Abstract B44: Protein interactions involving LARP1 in chemotherapy resistant ovarian cancer cells
Authors: Stavraka Chara , Mura Manuela , Fischer Roman , Thezenas Marie-Laetitia , Maghami Sadaf Ghaem , Chettle James , Buluwela Laki , Kessler Benedikt , Blagden Sarah P. 
Published: May 2017

Abstract
Ovarian cancer (OC) is the most lethal gynecological malignancy accounting for 152,000 deaths annually worldwide. Due to the lack of a validated diagnostic tool, patients usually present with disseminated disease and the majority will develop resistance to platinum chemotherapy. Resensitizing OC to cisplatin-based chemotherapy is an unmet clinical need. The RNA-binding protein LARP1 is highly expressed in OC and is a post-transcriptional regulator of cell survival and tumorigenesis. LARP1 depletion using RNA interference (RNAi) restores platinum sensitivity in cisplatin-resistant OC cell lines and shows a synergistic anti-tumour effect with cisplatin. We explored the effect of this resensitization on the efficiency of protein translation using the Surface Sensing of Translation (SUnSET) method. Whilst cisplatin-induced genotoxic stress attenuated de novo protein synthesis in platinum sensitive OVCAR3 cells, this was not observed in platinum-resistant OVCAR8 cells where residual protein synthesis was maintained. However this residual translation was completely abolished after RNAi to LARP1 suggesting that, in the OVCAR8 cells, LARP1 maintains protein synthesis during genotoxic stress. Although LARP1 is known to bind Poly A binding protein (PABP) we questioned whether other interacting partners might also regulate this response. Using immunoprecipitation followed by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) in OVCAR3 and OVCAR8 cells before and after cisplatin treatment, we identified PABPC1, PABPC4 and YB-1 as strong interactors with LARP1. By western blotting, Duolink Proximity Ligation Assay and Immunofluorescence we then confirmed these candidates as being complexed with LARP1. We are currently elucidating the functional role of these interactions on the LARP1-mediated genotoxic stress response with the overall aim of identifying therapeutic strategies to overcome platinum-resistance in ovarian cancer.
Citation Format: Chara Stavraka, Manuela Mura, Roman Fischer, Marie-Laetitia Thezenas, Sadaf Ghaem Maghami, James Chettle, Laki Buluwela, Benedikt Kessler, Sarah P. Blagden. Protein interactions involving LARP1 in chemotherapy resistant ovarian cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B44.
Abstract B45: Endometrial cancer microbiome signature and its implications for carcinogenesis
Authors: Walther-Antonio Marina , Chen Jun , Multinu Francesco , Hokenstad Alexis , Distad Tammy , Cheek Heidi , Keeney Gary , Creedon Douglas , Nelson Heidi , Mariani Andrea , Chia Nicholas 
Published: May 2017

Abstract
Endometrial cancer studies have led to a number of well-defined but mechanistically unconnected genetic and environmental risk factors. One of the emerging modulators between environmental triggers and genetic expression is the microbiome. Because of the inflammatory display in endometrial cancer, we set out to inquire about the composition of the uterine microbiome and its putative role in endometrial cancer. We undertook a pilot study of the microbiome in 238 samples taken from different locations along the entire female reproductive tract in hysterectomy patients with endometrial cancer (n=17), patients with endometrial hyperplasia (n=4) and patients afflicted with a benign uterine condition (n=10). Samples were collected aseptically both in the operating room and the pathology laboratory. Following DNA extraction, the 16S rDNA (V3-V5 region) microbial gene was amplified and sequenced to identify the microbiota present. The microbiome sequencing revealed a structural microbiome shift in the cancer and hyperplasia cases, distinguishable from the benign cases (p=0.01). Several taxa were found to be significantly enriched in samples belonging to the endometrial cancer cohort: Firmicutes (Anaerostipes, ph2, Dialister, Peptoniphilus, 1-68, Ruminococcus, and Anaerotruncus), Spirochaetes (Treponema), Actinobacteria (Atopobium), Bacteroidetes (Bacteroides and Porphyromonas), and Proteobacteria (Arthrospira). Of particular relevance, the simultaneous presence of Atopobium vaginae and an uncultured representative of the Porphyromonas sp. (99% match to P.somerae) were found to be predictive of the disease status (sensitivity 73-93%; specificity 67-90%, AUC 0.918). Sensitivity is increased to 100% if combined with a high vaginal pH (&gt;4.5), although specificity is decreased to 60%. Although our numbers are low, the microbiome signature of hyperplasia was even more distinct from benign disease than endometrial cancer itself. This is suggestive of an early microbiome role in the disease. Given the pathogenic profile of the identified microorganisms these findings raise the possibility of a microbiome role in the etiology or progression of endometrial cancer that should be further investigated.
Citation Format: Marina Walther-Antonio, Jun Chen, Francesco Multinu, Alexis Hokenstad, Tammy Distad, Heidi Cheek, Gary Keeney, Douglas Creedon, Heidi Nelson, Andrea Mariani, Nicholas Chia. Endometrial cancer microbiome signature and its implications for carcinogenesis. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr B45.
Abstract IA08: Therapeutic resistance and feedback loops
Authors: Zhao Jean J. 
Published: May 2017

Abstract
Therapeutic resistance is a major obstacle in the clinic. Utilizing our novel genetically engineered mouse models (GEMMs) of breast cancer driven by inducible expression of PIK3CAH1047R or a wildtype HER2, coupled with pharmacological approaches, we identified a number of significant resistance mechanisms to PI3K- or HER2-targeted therapy. For example, we found spontaneous focal amplification of Met and Myc, recurrent mutations in Ras and β-catenin, and compensatory activation of the MAPK pathway render resistance to PI3K inhibition. We recently identified Cyclin D1-CDK4 mediated resistance to HER2-targeted therapy through a signaling feedback loop. More importantly, our results led to the design of a randomized phase II trial examining a CDK4/6 inhibitor plus trastuzumab as a regimen for patients with metastatic, refractory HER2+ breast cancer. In addition to GEMMs, we have led the efforts at DFCI to establish and characterize novel breast cancer patient-derived xenograft (PDX) models, with an emphasis on brain metastases, an emerging clinical challenge. I will discuss how we have used these models to discover a therapeutic strategy that overcomes resistance and yields durable remission of brain metastases of HER2+ breast cancer in animals.
Citation Format: Jean J. Zhao. Therapeutic resistance and feedback loops. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr IA08.
Abstract IA15: Novel approaches for targeting MYC
Authors: Tansey William 
Published: May 2017

Abstract
The MYC family (c-, L-, and N-MYC) is one of the most important groups of proteins in human cancer. More than 50% of all malignancies overexpress at least one MYC family member, and estimates suggest that upwards of 100,000 Americans die from cancer every year as a result of inappropriate MYC expression or activity. Preclinical mouse models have demonstrated that perturbing MYC function in preexisting cancers promotes frank tumor regression, establishing MYC proteins as bonafide and high-value targets for discovery of broadly effective anti-cancer therapies.
Despite the potential of MYC inhibitors to impact cancer therapy, efforts to discover MYC inhibitors are stymied by numerous factors, including an absence of MYC interaction partners with characteristics that make them amenable to drug discovery efforts. The best understood MYC interaction partner, MAX, is required for MYC to assemble a competent DNA-binding module and would theoretically be a superb target for anti-MYC therapies. The MYC–MAX interaction, however, encompasses more that 1800 Å2 of buried protein surface, making it difficult to effectively disrupt by a small molecule with drug-like properties. Breaking the stalemate in drugging MYC requires a fresh perspective on how MYC functions and where the vulnerabilities in its molecular mechanisms of action lie.
Structure-function studies have delineated a potent activation domain at the amino-terminus of MYC and a DNA-binding domain at the carboxy-terminus, but the central portion between these domains has not been studied in detail. To rectify this deficit, we recently initiated screens to identify proteins that bind to the central portion of MYC, with the idea that these proteins would reveal new aspects of MYC regulation or function; some of which may expose new ways to target MYC activity. One novel MYC-interaction partner to emerge from this screen was WDR5.
WDR5 is a chromatin-associated protein that co-binds with MYC at a majority of its target genes. MYC binds weakly to WDR5 by engaging a structured hydrophobic cleft on one side of the WDR5 protein. Mutations in MYC that disrupt interaction with WDR5 block the ability of MYC to bind chromatin and disable its tumorigenic properties in mice, demonstrating that WDR5 is a critical co-factor for MYC. These studies led to a revised model for target gene recognition by MYC in which WDR5 facilitates the recruitment of MYC/MAX complexes to chromatin, and revealed that the MYC–WDR5 interface is a tractable surface for small molecule inhibition. In collaboration with the laboratory of Dr. Stephen Fesik we seek to discover and validate drug-like molecules that disrupt the MYC–WDR5 interaction and explore their utility in cell and animal-based models of cancer.
Citation Format: William Tansey. Novel approaches for targeting MYC. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr IA15.
Abstract IA27: Protein methyltransferase inhibitors as precision cancer therapeutics: From bench to bedside to bench
Authors: Copeland Robert A. 
Published: May 2017

Abstract
The protein methyltransferases (PMTs) constitute a class of enzymes that catalyze the methylation of lysine or arginine residues on histones and other proteins. A number of PMTs have been shown to be genetically altered in cancers through, for example, gene amplification, chromosomal translocations, point mutations and synthetic lethal relationships. The enzyme EZH2 provides a representative example of altered PMTs that act as genetic drivers of specific human cancers. Point mutations of EZH2 are found in a subset of non-Hodgkins lymphoma patients; the enzymatic activity of both wild type and mutant EZH2 are required for pathogenesis in these patients. Also, deletion of the INI1 or SMARCA4 subunit of the SWI/SNF chromatin-remodeling complex occur in a number of cancer types. For example, INI1 is deleted in nearly all malignant rhabdoid tumors (MRTs), a cancer found mainly in children that carries a particularly poor prognosis. Similarly, the SMARCA4 subunit of SWI/SNF is deleted, for example, in malignant rhabdoid tumor of the ovary (MRTO, also referred to as small cell carcinoma of the ovary hypercalcemic type), an aggressive cancer affecting young women. An antagonistic relationship has been demonstrated between the biochemical action on chromatin of the SWI/SNF complex and EZH2 (in the context of the polycomb repressive complex 2), that is relieved in MRTs due to the INI1 deletion. MRTs and other INI1- or SMARCA4-negative cancers therefore demonstrate increased reliance on the enzymatic activity of EZH2 for proliferation, and we have shown that MRT cells deficient in INI1 are selectively killed by inhibition of EZH2 in cell culture and in mouse xenograft models. Drug discovery efforts have yielded a potent, selective inhibitor of EZH2, tazemetostat (EPZ-6438), that has now transitioned into phase 2 clinical trials. This inhibitor affects the appropriate histone methyl marks in cells, leads to selective cell killing that is dependent on genetic lesions associated with EZH2 activity and effects tumor growth inhibition in xenograft models. Combining tazemetostat with other treatment modalities for non-Hodgkins lymphoma results in dramatic synergy of anti-proliferative activity in preclinical models. Results of preclinical and phase 1 clinical studies of tazemetostat will be presented.
Citation Format: Robert A. Copeland. Protein methyltransferase inhibitors as precision cancer therapeutics: From bench to bedside to bench. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr IA27.
The Perception of Daily Temperatures as Evidence of Global Warming
Authors: Broomell Stephen B. , Winkles Jon-Francis , Kane Patrick Bodilly 
Published: May 2017

Abstract
Unlike the scientific definition of global warming (GW), public discussion often links the existence of GW to daily temperatures rather than long-term averages. Previous research found that daily weather is perceived as personal experiences with GW. Additionally, prior beliefs about GW can affect interpretations of such experiences as evidence for the existence of GW. However, previous studies demonstrating that beliefs affect interpretations of experiences were based on correlational designs—limiting causal inferences—and relied only on self-reports of remembered personal experiences instead of direct interpretations of weather. The authors present the first randomized experiment investigating how people interpret daily temperatures in terms of the evidence that it provides about GW, clarifying the psychological causes for different interpretations of the same experiences across individuals. They test the influence of knowledge about (and beliefs in) GW on the interpretation of daily temperatures across two framing conditions labeled weather (interpreting a temperature as abnormal weather) and climate (interpreting a temperature as evidence of GW). The authors use signal detection theory to measure the decision-maker’s (a) ability to discriminate between temperatures, called sensitivity, and (b) threshold for describing a temperature as abnormal, called the decision threshold. The results replicate previous research finding a motivational distortion in interpreting temperatures as evidence of GW and further find belief-consistent distortions in decision thresholds while observing no measurable change in sensitivity. In other words, people know when temperatures are abnormally hot, but classify ambiguous events (i.e., less extreme abnormalities) differently based on their beliefs in GW.