bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract IA09: Therapy of lymphoma inspired by functional and structural genomics
Authors: Staudt Louis M.
Published: November 2015

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous diagnostic category that is comprised of two prominent molecular subtypes, termed activated B cell-like (ABC) and germinal center B cell-like (GCB). These DLBCL subtypes are now viewed as molecularly distinct diseases since they arise from distinct stages of normal B cell development, require distinct recurrent genetic abnormalities to become malignant, have distinct cure rates with current chemotherapy regimens, and respond differentially to targeting agents. We defined a chronic active form of B cell receptor (BCR) signaling that activates NF-kB in ABC DLBCLs. Such ABC DLBCLs are killed by knockdown of BCR signaling components, such as the kinase BTK or components of the BCR itself. Over one fifth of ABC DLBCLs have mutations affecting the CD79B or CD79A subunits of the BCR that augment BCR signaling. To attack chronic active BCR signaling therapeutically, we initiated clinical trials in relapsed/refractory DLBCL of ibrutinib, an irreversible and highly selective inhibitor of BTK. Ibrutinib monotherapy induced a high rate of complete and partial responses in ABC DLBCL, while GCB DLBCL tumors rarely responded. Genetic analysis of responding tumors demonstrated an enrichment for those with CD79B mutations, but most responses were observed in tumors with wild type BCR subunits. This observation allowed us to define a non-genetic mechanism of BCR activation that depends on reactivity of the lymphoma BCR to self antigens. In addition to chronic active BCR signaling, the signaling adapter MyD88 is activated by oncogenic mutations in 40% of ABC DLBCL cases. Since these mutant MyD88 isoforms act in parallel to BCR signaling to activate the NF-kB pathway in ABC DLBCL, they might have been predicted to mitigate the clinical effects of ibrutinib. On the contrary, ABC DLBCL tumors with both CD79B and MYD88 mutations were highly responsive to ibrutinib, leading us to demonstrate that the BCR and MyD88 pathways positively regulate one another. To extend the efficacy of ibrutinib, we have identified additional therapeutic targets in the oncogenic signaling pathways in ABC DLBCL including: 1) ubiquitin ligases, such as LUBAC, that are required to assemble active signaling complexes downstream of the BCR; 2) the kinase IRAK4, which mediates oncogenic MyD88 signaling; 3) the PI3 kinase pathway, which is activated by chronic active BCR signaling; 4) BCL2, which is expressed highly in most ABC DLBCL tumors and is the target of recurrent amplifications. Several synergistic, mechanism-based drug combinations that exploit these redundant survival pathways will be presented.

Citation Format: Louis M. Staudt. Therapy of lymphoma inspired by functional and structural genomics. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr IA09.
Abstract IA13: Deconvoluting the molecular circuitry of cancerous cells with high-throughput experimentation
Authors: Lum Lawrence
Published: November 2015

Developmentally important signal transduction pathways such as those controlled by the secreted Wnt and Hedgehog (Hh) ligands are frequently exploited in cancerous cells to promote unfettered growth. We describe functional and chemical genomics-based efforts to recover actionable mechanisms sustaining cancer-associated Wnt and Hh signaling. Our findings extend the portfolio of druggable enzymes with anti-cancer relevance and reveal novel prosurvival mechanisms in cancerous cells.

Citation Format: Lawrence Lum. Deconvoluting the molecular circuitry of cancerous cells with high-throughput experimentation. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr IA13.
Abstract PR01: Identifying clinically important somatic mutations through a knowledge-based approach
Authors: Ainscough Benjamin J. , Griffith Malachi , Kunisaki Jason , Coffman Adam , McMichael Joshua F. , Eldred James M. , Walker Jason R. , Fulton Robert S. , Wilson Richard K. , Griffith Obi L. , Mardis Elaine R.
Published: November 2015

Large-scale tumor sequencing projects, like The Cancer Genome Atlas (TCGA), have implicated thousands of somatic mutations in cancer. These initiatives have incentivized many improvements in somatic variant detection. However, we have observed that important pathogenic variants are often missed due to stringent filtering, tumor heterogeneity, tumor contamination of normal, low tumor purity, alignment challenges, and other issues. These idiosyncrasies can impede variant detection algorithms from reliably calling even the most clinically relevant variants. To rescue this missed variation we devised a knowledge based variant identification strategy. We mined the literature and other variant databases for pathogenic variation and assembled them into an integrated Database of Curated Mutations (DoCM - www.docm.info). The DoCM contains 488 variants across 63 genes implicated in 34 cancer types. We developed an algorithm to identify any pathogenic variant signal, for all variants in the DoCM, in aligned sequence data. As a proof of principle, we applied this approach to four cancer types sequenced by TCGA: acute myeloid leukemia (AML), breast cancer, ovarian carcinoma, and uterine corpus endometrial carcinoma. Obvious sequencing and alignment errors, like variants in homopolymer runs, were excluded from subsequent analysis by manual review. Across these four TCGA projects, which includes 1,840 individuals, 1,757 clinically relevant variants were identified, 1,223 of which had not been previously reported in TCGA studies. To validate this approach, custom capture probes were designed for all of the DoCM variants, new libraries constructed and deep sequencing performed on 96 tumor and matched normal samples from the AML and breast cancer TCGA projects. Following this strategy, we were able to confirm the rescue of clinically relevant somatic mutations that were missed in the original TCGA analysis. We propose a knowledge-driven variant detection approach be considered as standard practice to avoid false-negative calls of events likely to be clinically relevant

Citation Format: Benjamin J. Ainscough, Malachi Griffith, Jason Kunisaki, Adam Coffman, Joshua F. McMichael, James M. Eldred, Jason R. Walker, Robert S. Fulton, Richard K. Wilson, Obi L. Griffith, Elaine R. Mardis. Identifying clinically important somatic mutations through a knowledge-based approach. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr PR01.
Abstract PR04: Cancer drug response networks built for comparative cancer pharmacogenomics identifies combination therapies for repositioning
Authors: Brubaker Doug , Elena Svenson , Smith Kai , Monroe Maya , Ryu Christopher , Chance Mark R. , Narla Goutham , Bebek Gurkan
Published: November 2015

We present an integrative framework for classifying drug response: CAncer Drug Response nEtworks (CADREs). We built CADREs for drugs with differential sensitivity profiles in cancer cell lines by integrating baseline copy number, gene expression, and drug sensitivity data for the cell lines. The nodes in the network are drugs and the edges are weighted according to the number of shared copy number variations, differentially expressed genes, and dysregulated pathways present in sensitive cell lines at baseline. These baseline features were mapped into pathways to generate a Pathway CADRE, and were also integrated into a differential gene expression and copy number Feature CADRE. CADREs were built for breast, ovarian, and endometrial cancers individually and combined to assess shared and unique features of drug sensitivity. Analyzing CADRE clusters associated multiple gene features and pathways with sensitivity to frontline therapies used in combination in these cancers. We identified four clusters of breast cancer drugs whose effectiveness is driven by a shared core of pathways. Compounds that were used in combination in clinical trials tended to not share an edge or are completely disconnected in networks. Specifically, ten such drug pairs in our breast CADREs have been found to work in combination in breast cancer and an additional five have been used in combination in other cancers, representing opportunities for repositioning these combinations in breast cancer. Examining highly interconnected CADRE nodes gave us an understanding for compounds that might work best together.

Citation Format: Doug Brubaker, Svenson Elena, Kai Smith, Maya Monroe, Christopher Ryu, Mark R. Chance, Goutham Narla, Gurkan Bebek. Cancer drug response networks built for comparative cancer pharmacogenomics identifies combination therapies for repositioning. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr PR04.
Abstract PR05: Using genome-scale CRISPR-mediated loss-of-function and gain-of-function screens to analyze gene-drug interactions in cancer
Authors: Gilbert Luke A. , Tanenbaum Marvin E. , Horlbeck Max A. , Adamson Britt , Villalta Jacqueline E. , Vale Ronald D. , Kampmann Martin , Weissman Jonathan S.
Published: November 2015

Drug resistance remains a pressing problem in cancer therapy. One major mode of resistance involves altered gene expression in the cancer cell. Knowing which genes can promote resistance or sensitivity to a specific cancer drug could pave the way for the development of new treatment strategies that minimize cancer drug resistance. Genome-scale loss-of-function and gain-of-function screens can be used to discover novel gene-drug interactions in cancer. RNAi and cDNA/ORF overexpression libraries have previously been used to conduct such screens, but both have drawbacks. RNAi has off-target effects, which can lead to false-positive results. cDNAs/ORFs are usually kilobases long and can be challenging to clone, verify and maintain in an overexpression library. Our recently developed CRISPR-based screening methods address these shortcomings. The technology combines different catalytically inactive Cas9 (dCas9) fusion proteins and uniquely designed short guide RNAs (sgRNA) allowing us to repress (CRISPRi) or activate (CRISPRa) the transcription of specific genes.

CRISPRi uses KRAB, a repressive chromatin modifier domain, fused to dCas9. CRISPRa uses the sunCas9 system where a peptide epitope chain is fused to dCas9 and recruits multiple copies of VP64, a transcriptional activator, attached to an intracellular single-chain antibody directed against the epitope. The gene-specific region of sgRNAs is at most 25 bases, so with the help of massively parallel oligonucleotide synthesis and next-generation sequencing, we cloned and verified genome-scaled sgRNA libraries targeting 15,977 human protein-coding genes. When used for screening, we showed that CRISPRi has minimal off-target effects, one reason being that repression is highly sensitive to mismatches between sequences of the target DNA and the sgRNA.

Citation Format: Luke A. Gilbert, Marvin E. Tanenbaum, Max A. Horlbeck, Britt Adamson, Jacqueline E. Villalta, Ronald D. Vale, Martin Kampmann, Jonathan S. Weissman. Using genome-scale CRISPR-mediated loss-of-function and gain-of-function screens to analyze gene-drug interactions in cancer. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr PR05.
Abstract PR15: Functional analysis of diverse oncogenic driver mutations using an isogenic cell line library identifies novel drug responses and alterations in metabolism
Authors: Martins Maria M. , Zhou Alicia Y. , Corella Alexandra , Horiuchi Dai , Yau Christina , Rakshandehroo Taha , Gordan John D. , Levin Rebecca S. , Johnson Jeff , Jascur John , Shales Mike , Sorrentino Antonio , Cheah Jaime , Clemons Paul A. , Shamji Alykhan , Schreiber Stuart , Schreiber Stuart , Krogan Nevan J. , Shokat Kevan M. , Shokat Kevan M. , McCormick Frank , Nomura Daniel , Bandyopadhyay Sourav , Goga Andrei
Published: November 2015

There is an urgent need in oncology to link molecular aberrations in tumors with altered cellular behaviors, such as metabolic derangements, and to identify novel therapeutics for cancer treatment. We have sought to identify synthetic-lethal genetic interactions that cancer cells acquire in the presence of specific mutations. Using engineered isogenic cells, we generated an unbiased and quantitative chemical-genetic interaction map that measures the influence of 51 aberrant cancer genes on 90 drug responses. The dataset strongly predicts drug responses found in cancer cell line collections, indicating that isogenic cells can model more complex cellular contexts. Applied to triple-negative breast cancer, we report clinically actionable interactions with the MYC oncogene including resistance to PI3K/AKT pathway inhibitors and an unexpected sensitivity to dasatinib through LYN inhibition in a synthetic-lethal manner. These studies provide new drug and biomarker pairs for clinical investigation. We have also performed global metabolomics analysis in a subset of the isogenic cell lines demonstrating alterations in metabolic pathways that are shared across multiple oncogenes, as well as those that are distinct to specific oncogenic drivers. This scalable approach enables the prediction of drug responses from patient data and can be used to accelerate the development of new genotype-directed therapies.

Citation Format: Maria M. Martins, Alicia Y. Zhou, Alexandra Corella, Dai Horiuchi, Christina Yau, Taha Rakshandehroo, John D. Gordan, Rebecca S. Levin, Jeff Johnson, John Jascur, Mike Shales, Antonio Sorrentino, Jaime Cheah, Paul A. Clemons, Alykhan Shamji, Stuart Schreiber, Stuart Schreiber, Nevan J. Krogan, Kevan M. Shokat, Kevan M. Shokat, Frank McCormick, Daniel Nomura, Sourav Bandyopadhyay, Andrei Goga. Functional analysis of diverse oncogenic driver mutations using an isogenic cell line library identifies novel drug responses and alterations in metabolism. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr PR15.
Anomalous Posterior Arch of Atlas: A Rare Cause for Craniovertebral Junction Compression
Authors: Upadhyaya Sunil , Ganapathy Sibhi , Nair Rajesh , Menon Girish
Published: November 2015

Congenital hypoplasia of the anterior and posterior arch of the atlas has been described in the literature. Currarino and associates classified this into various types based on the part of the arch that was hypoplastic. Gin and associates stated that posterior atlantal anomalies were more frequently encountered than anterior arch anomalies. Rarely do these anomalies present in the absence of genetic syndromes. Here, we describe our clinical experience of an anomalous posterior atlantal arch in a nonsyndromic patient.
A Case of Mature Natural Killer-Cell Neoplasm Manifesting Multiple Choroidal Lesions: Primary Intraocular Natural Killer-Cell Lymphoma
Authors: Tagawa Yoshiaki , Namba Kenichi , Ogasawara Reiki , Kanno Hiromi , Ishida Susumu
Published: November 2015

Purpose: Natural killer (NK) cell neoplasm is a rare disease that follows an acute course and has a poor prognosis. It usually emerges from the nose and appears in the ocular tissue as a metastasis. Herein, we describe a case of NK-cell neoplasm in which the eye was considered to be the primary organ. Case: A 50-year-old female displayed bilateral anterior chamber cells, vitreous opacity, bullous retinal detachment, and multiple white choroidal mass lesions. Although malignant lymphoma or metastatic tumor was suspected, various systemic examinations failed to detect any positive results. A vitrectomy was performed OS; however, histocytological analyses from the vitreous sample showed no definite evidence of malignancy, and IL-10 concentration was low. Enlarged choroidal masses were fused together. Three weeks after the first visit, the patient suddenly developed an attack of fever, night sweat, and hepatic dysfunction, and 5 days later, she passed away due to multiple organ failure. Immunohistochemisty and in situ hybridization revealed the presence of atypical cells positive for CD3, CD56, and Epstein-Barr virus-encoded RNAs, resulting in the diagnosis of NK-cell neoplasm. With the characteristic clinical course, we concluded that this neoplasm was a primary intraocular NK-cell lymphoma. Conclusions: This is the first report to describe primary intraocular NK-cell neoplasm. When we encounter atypical choroidal lesions, we should consider the possibility of NK-cell lymphoma, even though it is a rare disease.
Increased Contractile Response to Noradrenaline Induced By Factors Associated with the Metabolic Syndrome in Cultured Small Mesenteric Arteries
Authors: Blædel Martin , Sams Anette , Boonen Harrie C.M. , Sheykhzade Majid
Published: November 2015

This study investigated the effect of the metabolic syndrome associated risk factors hyperglycemia (glucose [Glc]), hyperinsulinemia (insulin [Ins]) and low-grade inflammation (tumor necrosis factor α [TNFα]) on the vasomotor responses of resistance arteries. Isolated small mesenteric arteries from 3-month-old Sprague-Dawley rats, were suspended for 21-23 h in tissue cultures containing either elevated Glc (30 mmol/l), Ins (100 nmol/l), TNFα (100 ng/ml) or combinations thereof. After incubation, the vascular response to noradrenaline (NA), phenylephrine, isoprenaline and NA in the presence of propranolol (10 µmol/l) was measured by wire myography. Results: Arteries exposed only to combinations of the risk factors showed a significant 1.6-fold increase in the contractile NA sensitivity, which suggests that complex combinations of metabolic risk factors might lead to changes in vascular tone.
The North American Soil Moisture Database: Development and Applications
Authors: Quiring Steven M. , Ford Trent W. , Wang Jessica K. , Khong Angela , Harris Elizabeth , Lindgren Terra , Goldberg Daniel W. , Li Zhongxia
Published: November 2015

Soil moisture is an important variable in the climate system that integrates the combined influence of the atmosphere, land surface, and soil. Soil moisture is frequently used for drought monitoring and climate forecasting. However, in situ soil moisture observations are not systematically archived and there are relatively few national soil moisture networks. The lack of observed soil moisture data makes it difficult to characterize long-term soil moisture variability and trends. The North American Soil Moisture Database (NASMD) is a new high-quality observational soil moisture database. It includes over 1,800 monitoring stations in the United States, Canada, and Mexico, making it the largest collections of in situ soil moisture observations in North America. Data are collected from multiple sources, quality controlled, and integrated into an online database (soilmoisture.tamu.edu). Here we describe the development of the database, including quality control/quality assurance, standardization, and collection of metadata. The utility of the NASMD is demonstrated through an analysis of the inter- and intraannual variability of soil moisture from multiple networks. The NASMD is a useful tool for drought monitoring and forecasting, calibrating/validating satellites and land surface models, and documenting how soil moisture influences the climate system on seasonal to interannual time scales.
The Dissipation of Trapped Lee Waves. Part II: The Relative Importance of the Boundary Layer and the Stratosphere
Authors: Hills Matthew O. G. , Durran Dale R. , Blossey Peter N.
Published: November 2015

Decaying trapped waves exert a drag on the large-scale flow. The two most studied mechanisms for such decay are boundary layer dissipation and leakage into the stratosphere. If the waves dissipate in the boundary layer, they exert a drag near the surface, whereas, if they leak into the stratosphere, the drag is exerted at the level where the waves dissipate aloft. Although each of these decay mechanisms has been studied in isolation, their relative importance has not been previously assessed.

Here, numerical simulations are conducted showing that the relative strength of these two mechanisms depends on the details of the environment supporting the waves. During actual trapped-wave events, the environment often includes elevated inversions and strong winds aloft. Such conditions tend to favor leakage into the stratosphere, although boundary layer dissipation becomes nonnegligible in cases with shorter resonant wavelengths and higher tropopause heights. In contrast, idealized two-layer profiles with constant wind speeds and high static stability beneath a less stable upper troposphere support lee waves that are much more susceptible to boundary dissipation and relatively unaffected by the presence of a stratosphere. One reason that trapped waves in the two-layer case do not leak much energy upward is that the resonant wavelength is greatly reduced in the presence of surface friction. This reduction in wavelength is well predicted by the linear inviscid equations if the basic-state profile is modified a posteriori to include the shallow ground-based shear layer generated by surface friction.
The megaphone of the people? Spanish SentiStrength for real-time analysis of political tweets
Authors: Vilares David , Thelwall Mike , Alonso Miguel A.
Published: November 2015

Twitter is an important platform for sharing opinions about politicians, parties and political decisions. These opinions can be exploited as a source of information to monitor the impact of politics on society. This article analyses the sentiment of 2,704,523 tweets referring to Spanish politicians and parties from a month in 2014–2015. The article makes three specific contributions: (a) enriching SentiStrength, a fast unsupervised sentiment strength detection system, for Spanish political tweeting; (b) analysing how linguistic phenomena such as negation, idioms and character duplication influence Spanish sentiment strength detection accuracy; and (c) analysing Spanish political tweets to rank political leaders, parties and personalities for popularity. Sentiment in Twitter for key politicians broadly reflects the main official polls for popularity but not for voting intention. In addition, the data suggests that the primary role of Twitter in politics is to select and amplify political events published by traditional media.
Elusive ditrysian phylogeny: an account of combining systematized morphology with molecular data (Lepidoptera)
Authors: Heikkilä Maria , Mutanen Marko , Wahlberg Niklas , Sihvonen Pasi , Kaila Lauri
Published: November 2015

Background

Ditrysia comprise close to 99 % of all butterflies and moths. The evolutionary relationships among the ditrysian superfamilies have received considerable attention in phylogenetic studies based on DNA and transcriptomic data, but the deepest divergences remain for large parts unresolved or contradictory. To obtain complementary insight into the evolutionary history of the clade, and to test previous hypotheses on the subdivision of Ditrysia based on morphology, we examine the morphology of larvae, pupae and adult males and females of 318 taxa representing nearly all ditrysian superfamilies and families. We present the most comprehensive morphological dataset on Ditrysia to date, consisting of over 500 morphological characters. The data are analyzed alone and combined with sequence data (one mitochondrial and seven nuclear protein-coding gene regions, sequenced from 422 taxa). The full dataset consists of 473 exemplar species. Analyses are performed using maximum likelihood methods, and parsimony methods for the morphological dataset. We explore whether combining morphological data and DNA-data can stabilize taxa that are unstable in phylogenetic studies based on genetic data only.

Results

Morphological characters are found phylogenetically informative in resolving apical nodes (superfamilies and families), but characters serving as evidence of relatedness of larger assemblages are few. Results include the recovery of a monophyletic Tineoidea, Sesioidea and Cossoidea, and a stable position for some unstable taxa (e.g. Epipyropidae, Cyclotornidae, Urodoidea + Schreckensteinioidea). Several such taxa, however, remain unstable even though morphological characters indicate a position in the tree (e.g. Immidae). Evidence supporting affinities between clades are suggested, e.g. a novel larval synapomorphy for Tineidae. We also propose the synonymy of Tineodidae with Alucitidae, syn. nov.

Conclusions

The large morphological dataset provides information on the diversity and distribution of morphological traits in Ditrysia, and can be used in future research on the evolution of these traits, in identification keys and in identification of fossil Lepidoptera. The “backbone” of the phylogeny for Ditrysia remains largely unresolved. As previously proposed as an explanation for the scarcity of molecular signal in resolving the deeper nodes, this may be due to the rapid radiation of Ditrysia in the Cretaceous.
Advances in understanding and managing bullous pemphigoid
Authors: Zhao Cathy Y. , Murrell Dedee F.
Published: November 2015

Bullous pemphigoid (BP) is the commonest subtype of autoimmune blistering disease in most countries of the world. It occurs most frequently in elderly patients and is characterised clinically by large, tense blisters in the skin preceded by urticarial plaques and pruritus. Immunopathologically, it is characterised by autoantibodies directed against the 180 kD antigen (BP180) and the 230 kD antigen (BP230). New knowledge regarding BP is being continually uncovered. This article reviews the recent advances in BP, including newer diagnostic tests, standardised outcome measures and emerging therapeutic options, as well as the evidence supporting their use.
Research Commentary—Informing Privacy Research Through Information Systems, Psychology, and Behavioral Economics: Thinking Outside the “APCO” Box
Authors: Dinev Tamara , McConnell Allen R. , Smith H. Jeff
Published: November 2015

Recently, several researchers provided overarching macromodels to explain individuals’ privacy-related decision making. These macromodels—and almost all of the published privacy-related information systems (IS) studies to date—rely on a covert assumption: responses to external stimuli result in deliberate analyses, which lead to fully informed privacy-related attitudes and behaviors. The most expansive of these macromodels, labeled “Antecedents–Privacy Concerns–Outcomes” (APCO), reflects this assumption. However, an emerging stream of IS research demonstrates the importance of considering principles from behavioral economics (such as biases and bounded rationality) and psychology (such as the elaboration likelihood model) that also affect privacy decisions. We propose an enhanced APCO model and a set of related propositions that consider both deliberative (high-effort) cognitive responses (the only responses considered in the original APCO model) and low-effort cognitive responses inspired by frameworks and theories in behavioral economics and psychology. These propositions offer explanations of many behaviors that complement those offered by extant IS privacy macromodels and the information privacy literature stream. We discuss the implications for research that follow from this expansion of the existing macromodels.
Jumps in High-Frequency Data: Spurious Detections, Dynamics, and News
Authors: Bajgrowicz Pierre , Scaillet Olivier , Treccani Adrien
Published: November 2015

Applying tests for jumps to financial data sets can lead to an important number of spurious detections. Bursts of volatility are often incorrectly identified as jumps when the sampling is too sparse. At a higher frequency, methods robust to microstructure noise are required. We argue that whatever the jump detection test and the sampling frequency, a large number of spurious detections remain because of multiple testing issues. We propose a formal treatment based on an explicit thresholding on available test statistics. We prove that our method eliminates asymptotically all remaining spurious detections. In Dow Jones stocks between 2006 and 2008, spurious detections can represent up to 90% of the jumps detected initially. For the stocks considered, jumps are rare events, they do not cluster in time, and no cojump affects all stocks simultaneously, suggesting jump risk is diversifiable. We relate the remaining jumps to macroeconomic news, prescheduled company-specific announcements, and stories from news agencies that include a variety of unscheduled and uncategorized events. The vast majority of news does not cause jumps but may generate a market reaction in the form of bursts of volatility.

This paper was accepted by Jérôme Detemple, finance.
In vivo Evaluation of Retinal and Choroidal Structure in a Mouse Model of Long-Lasting Diabetes. Effect of Topical Treatment with Citicoline
Authors: Maestroni Silvia , Preziosa Chiara , Capuano Valentina , Spinello Alice , Zucchiatti Ilaria , Gabellini Daniela , Lattanzio Rosangela , Bandello Francesco , Zerbini Gianpaolo
Published: November 2015

Recent evidences indicate early, diabetes-driven, retinal neurodegeneration as the origin of diabetic retinopathy. To verify the possibility to prevent the disease, we investigated in a mouse model of type 1 diabetes the effect of long-lasting hyperglycemia on retinal and choroidal structures and, in parallel, we tested the effect of topical treatment with the neuroprotective agent citicoline. Forty wild-type C57B6 mice were included in this study. Diabetes was induced by a single intravenous injection of alloxan. Five animals were considered as sham-treated controls, 15 animals as sham-treated diabetic mice, 5 animals as citicoline-treated controls and 15 animals as citicoline-treated diabetic mice. After eight months of diabetes in vivo analysis of the retina was performed using the Spectralis HRA (Heidelberg Retinal Angiography) + OCT. Neuroretinal abnormalities, in particular a significant narrowing of Retinal Nerve Fiber Layer (19.3 ± 2.2 vs 23.3 ± 2.4, ?m ± SD, p=0.01), Ganglion Cells/Inner Plexiform Layer (54.3 ± 5.1 vs 62.6 ± 4.0, p=0.03), Ganglion Cells Complex (73.9 ± 4.8 vs 83.8 ± 3.4, p=0.003) and Retinal thickness (223.8 ± 3.9 vs 236.7 ± 5.8, p=0.0004) were detected in the diabetic mouse that showed also a significant reduction of Choroidal thickness (67.4 ± 3.3 vs 84.7 ± 1.9, p=0.0001). In line with the hypothesis that neuroprotection might help preventing diabetic retinopathy, neuroretinal but not choroidal (choroid lacks a neuronal component) dysfunctions were prevented by citicoline. Altogether these findings demonstrate that diabetes-driven neuroretinal dysfunctions can be monitored in vivo by OCT in the mouse. Retinal neuroprotection as obtained by topical citicoline protects from these abnormalities suggesting this approach as a possible way to prevent diabetic retinopathy.
Bursting Right Eye and Total Lost with Blowout Fracture in a Child
Authors: Ceballos Ramón Navarro , Osorio Eduardo Manzano
Published: November 2015

This is a progressive demostration of severe damage to right orbit with bursting right eye. In this article we performed the treatment with enucleation and immediate reconstruction of orbital socket with blowout fracture with autologous implant of ear cartilage and series of reconstructive surgeries with the result to three years of accident.
Alteplase and Tenecteplase Confusion; Lack of E-Prescribing Interoperability Leads to Double Dosing; Accidental Overdoses Involving Fluorouracil Infusions
Authors: Cohen Michael R. , Smetzer Judy L.
Published: November 2015

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs.

Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers’ names will be published if desired. ISMP may be contacted at the address shown below.

Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters’ wishes as to the level of detail included in publications.
Approvals, Submission, and Important Labeling Changes for US Marketed Pharmaceuticals
Authors: Baker Danial E.
Published: November 2015

This monthly feature will help readers keep current on new drugs, new indications, dosage forms, and safety-related changes in labeling or use. Efforts have been made to ensure the accuracy of this information; however, if there are any questions, please let me know at danial.baker@wsu.edu .
Automatic Processing of Chromatograms in a High-Throughput Environment
Authors: Lytle Fred E , Julian Randall K
Published: November 2015

BACKGROUND

A major challenge in high-throughput clinical and toxicology laboratories is the reliable processing of chromatographic data. In particular, the identification, location, and quantification of analyte peaks needs to be accomplished with minimal human supervision. Data processing should have a large degree of self-optimization to reduce or eliminate the need for manual adjustment of processing parameters. Ultimately, the algorithms should be able to provide a simple quality metric to the batch reviewer concerning confidence about analyte peak parameters.

CONTENT

In this review we cover the basic conceptual and mathematical underpinnings of peak detection necessary to understand published algorithms suitable for a high-throughput environment. We do not discuss every approach appearing in the literature. Instead, we focus on the most common approaches, with sufficient detail that the reader will be able to understand alternative methods better suited to their own laboratory environment. In particular it will emphasize robust algorithms that perform well in the presence of substantial noise and nonlinear baselines.

The advent of fast computers with 64-bit architecture and powerful, free statistical software has made practical the use of advanced numeric methods. Proper choice of modern data processing methodology also facilitates development of algorithms that can provide users with sufficient information to support QC strategies including review by exception.
An Empirical Approach to Signature Peptide Choice for Selected Reaction Monitoring: Quantification of Uromodulin in Urine
Authors: Fu Qin , Grote Eric , Zhu Jie , Jelinek Christine , Köttgen Anna , Coresh Josef , Van Eyk Jennifer E
Published: November 2015

BACKGROUND

Many avenues have been proposed for a seamless transition between biomarker discovery data and selected reaction monitoring (SRM) assays for biomarker validation. Unfortunately, studies with the abundant urinary protein uromodulin have shown that these methods do not converge on a consistent set of surrogate peptides for targeted mass spectrometry. As an alternative, we present an empirical peptide selection work flow for robust protein quantification.

METHODS

We compared the relative SRM signal intensity of 12 uromodulin-derived peptides between tryptic digests of 9 urine samples. Pairwise CVs between the 12 peptides were 0.19–0.99. We used a correlation matrix to identify peptides that reproducibly tracked the amount of uromodulin protein and selected 4 peptides with robust and highly correlated SRM signals. Absolute quantification was performed with stable isotope–labeled versions of these peptides as internal standards and a standard curve prepared from a tryptic digest of purified uromodulin.

RESULTS

Absolute quantification of uromodulin in 40 clinical urine samples yielded interpeptide correlations of ≥0.984 and correlations of ≥0.912 with ELISA data. The SRM assays were linear over >3 orders of magnitude and had typical interdigest CVs of <10%, interinjection CVs of <7%, and intertransition CVs of <7%.

CONCLUSIONS

Comparing the apparent abundance of a plurality of peptides derived from the same target protein makes it possible to select signature peptides that are unaffected by the unpredictable confounding factors inevitably present in biological samples.
Aspetos técnicos a ter em conta nos incêndios de interface. Estudo de caso aplicado ao Chile
Authors: Castillo S. Miguel
Published: November 2015

Apresenta-se um resumo dos principais aspetos técnicos envolvidos no desenvolvimento da vulnerabilidade a incêndios em áreas de interface florestal-urbano. Recolheram-se dados procedentes de incêndios reais ocorrido nos últimos anos, especialmente de 2014, por ser considerado o ano mais catastrófico neste tipo de incêndios. Os resultados, com base no trabalho de campo e análise de previsão fogo, mostram que o tempo de resposta do primeiro ataque é o fator determinante, na possibilidade de sucesso para a contenção oportuna da propagação do fogo.
Risco de stress térmico num ambiente quente em contexto industrial
Authors: Morgado Mariana , Talaia Mário , Teixeira Leonor
Published: November 2015

O desconforto térmico é uma causa de insatisfação no trabalho fortemente associada a riscos de acidentes de trabalho. É neste contexto que o presente trabalho se insere, tendo como objetivo, através de índices térmicos, a identificação do padrão térmico dos espaços em estudo e dos postos de trabalho com maior risco a stress térmico, bem como ao conhecimento das sensações térmicas dos trabalhadores. O Departamento de Higiene e Segurança das indústrias estudadas valorizou os resultados para criar medidas que satisfaçam as necessidades em termos de conforto.
Bombeiros: o papel das emoções e do coping na satisfação com a profissão
Authors: Vara Natália , Queirós Cristina , Gonçalves Sónia P.
Published: November 2015

A profissão de bombeiro implica gerir situações stressantes e uma diversidade de emoções. Este estudo pretende compreender a influência das emoções expressas no trabalho sobre a satisfação com a profissão e perceber se esta é mediada pelas estratégias de coping. Os resultados revelaram que a combinação das emoções expressas no trabalho com as estratégias de coping pode aumentar a satisfação profissional e pode conduzir a uma melhor gestão das situações stressantes no trabalho (S. Folkman e R. Lazarus, 1991).
Construir e experimentar métodos participativos para desenvolver uma cultura de risco em São Paulo
Authors: Okamura Cintia , Lolive Jacques
Published: November 2015

Este artigo propõe-se apresentar a experiência que está sendo desenvolvida em São Paulo, num contexto urbano caracterizado pela coexistência de diferentes tipos de riscos, no qual as instituições responsáveis pela regulação de riscos sanitários e ambientais se defrontam com novos desafios para apresentar de forma adequada à sociedade situações ou contextos que a ameaçam. Assim, por meio de um projeto de pesquisa, propõe-se testar e construir metodologias pertinentes para contribuir com o desenvolvimento de uma cultura de risco que valoriza as práticasde prevenção e vigilância.
Mapeamento do risco de ravinamento na área de proteção ambiental Fernão Dias, sudeste do Brasil, a partir de lógica de decisão FUZZY
Authors: Ferreira Marcos César , Garófalo Danilo Trovó , Ferreira Marta Marujo
Published: November 2015

É apresentado um modelo espacial que utiliza regressão logística, classificação fuzzy e SIG, para mapear o risco de ravinamento. Este modelo utiliza os mapas: índice de vegetação; declividade; densidade de lineamentos estruturais e de estradas vicinais. A possibilidade de ocorrência de um evento de ravinamento, em relação a estes mapas, foi estimada através do odd ratio (OR). O modelo calcula o risco de ravinamento em cada pixel, a partir da soma ponderada de mapas temáticos, e utiliza como peso o valor de r2 obtido pela frequência de pontos de ravinamento observados em cada classe dos mapas temáticos.
As capturas de bacias hidrográficas: evidências morfotectônicas no contato da chapada com o relevo dissecado da bacia do rio Tijuco (MG)
Authors: Pereira Kátia Gisele De Oliveira , Pedrosa António De Sousa
Published: November 2015

A origem paleogeográfica da área de pesquisa conta com a ocorrência dos derrames vulcânicos que deram origem aos basaltos da Formação Serra Geral, rocha encontrada na base dos principais cursos d'água da região. Sobre eles ocorrem os arenitos do Grupo Bauru. Esse grupo é representado nesta área por: i) arenitos da Formação Marília; ii) a Formação Adamantina; iii) a Formação Uberaba. A área de pesquisa corresponde às bacias dos ribeirões Douradinho, Panga e Estiva, afluentes do rio Tijuco (MG), localizada no Oeste do Triângulo Mineiro no contato da chapada com o relevo dissecado do rio Tijuco (MG). Neste compartimento são encontradas intensas voçorocas alinhadas com as rupturas nas vertentes e, também, com o rebaixamento do nível de base.
Effect of multi-tree handling and tree-size on harvester performance in small-diameter hardwood thinnings
Authors: Erber Gernot , Holzleitner Franz , Kastner Maximilian , Stampfer Karl
Published: November 2015

Early thinnings are laborious and costly. Thus forest companies are searching for cost and time efficient ways to carry out this task. The studyâs purpose was to determine the productivity of the EF28 accumulating energy wood harvesting head in harvesting small-diameter hornbeam ( L.) undergrowth trees and evaluate the effect of its multi-tree handling (MTH) capacity on time consumption. The harvester was a wheeled, three-axle Komatsu 911. A time study of 7.1Â hours on 19Â plots, with a total area of 0.76 ha was conducted. On average, the harvested tree volume was 8Â dmÂ³ and the stand density was 2666 trees/ha. The productivity was modelled with MTH conduction, mean diameter at breast height and the number of trees handled per cycle as independent variables. On average, MTH took 27% longer per cycle, increased extracted volume per cycle by 33% and consequently increased productivity with 5.0%. In 71.9% of the cycles more than one tree was handled and if so, dimensions were smaller than in single-tree handling (5.8Â cm vs. 12.0Â cm). Maximum felling diameter of 23Â cm was about 15% smaller than in softwood (according to the manufacturerâs specifications) and the driver didnât exploit the EF28âs theoretical potential in terms of trees handled per cycle. It can be concluded that the head could significantly improve productivity in small-diameter wood procurement.Carpinus betulus
Контракция калибровочной группы электрослабой модели и ее естественные энергетические пределы
Authors: Громов Николай Алексеевич , Gromov Nikolai Alekseevich
Published: November 2015

Из первых принципов калибровочных теорий на уровне классических калибровочных полей рассматривается высоко- и низкоэнергетические поведение электрослабой модели.
Оба предела порождаются одной и той же контракцией калибровочной группы при разных согласованных преобразованиях пространства полей. Математический параметр контракции в обоих случаях физически интерпретируется как энергия.
Очень слабое взаимодействие нейтрино с веществом, особенно при малых энергиях, объясняется стремящимся к нулю контракционным параметром, зависящим от энергии нейтрино.
В высокоэнергетическом пределе все частицы электрослабой модели теряют массу, так что лагранжиан предельной модели содержит только безмассовые нейтральные $Z$-бозоны, безмассовые $u$-кварки, нейтрино и фотоны, а также их слабые и электромагнитные взаимодействия. Слабые взаимодействия становятся дальнодействующими и осуществляются посредством только нейтральных токов. Предельная модель отвечает развитию Вселенной в первую секунду после Большого взрыва.
Дискретный и непрерывный случаи в задаче о распространении волн в среде с памятью
Authors: Царицанский Анатолий Николаевич , Tsaritsanskiy Anatoly Nikolaevich
Published: November 2015

В работе рассматривается волновое уравнение для среды с памятью, полученное при исследовании усредненных моделей комбинированных сред и описывающее одномерный вариант закона Кельвина-Фойгхта вязкоупругих колебаний комбинированных сред. Задача состоит в определении функции, с физической точки зрения отвечающей за среднее смещение материала. Для этого с помощью формулы распространяющихся волн строится решение через общее решение системы первого порядка, в которой каждое уравнение является уравнением переноса вдоль соответствующей характеристики. Основной результат сформулирован в виде двух теорем для дискретной и непрерывной модификации уравнения. В работе также содержатся наглядные соображения, приводящие к построению классического решения уравнений.
Модель Изинга с дальним взаимодействием
Authors: Бирюков Александр Александрович , Biryukov Alexander Alexandrovich , Дегтярева Яна Владимировна , Degtyareva Yana Vladimirovna
Published: November 2015

Методом Монте-Карло исследуется фазовый переход в двумерной и трехмерной моделях Изинга с дальним взаимодействием спинов. Область взаимодействия каждого спина с окружающими его спинами характеризуется радиусом $R$. На основе численного моделирования показано, что температура фазового перехода $T_c$ зависит от радиуса $R$ области взаимодействия между спинами. Построена аналитическая функция $T_{c}(R)$, аппроксимирующая данную зависимость.
Сверхтонкая структура $S$-состояний мюонного дейтерия
Authors: Мартыненко Алексей Петрович , Martynenko Alexey Petrovich , Мартыненко Григорий Алексеевич , Martynenko Gregory Alexeevich , Сорокин Вячеслав Вадимович , Sorokin Vyacheslav Vadimovich , Фаустов Рудольф Николаевич , Faustov Rudolf Nikolaevich
Published: November 2015

В рамках квазипотенциального метода в квантовой электродинамике вычислены поправки порядка $\alpha^5$ и $\alpha^6$ в сверхтонкой структуре $S$-состояний мюонного дейтерия. Учтены релятивистские поправки, эффекты поляризации вакуума в первом, втором и третьем порядках теории возмущений, эффекты структуры и поправки на отдачу. Полученные численные значения сверхтонких расщеплений $\Delta E^{hfs}(1S)=50.2814$ мэВ ($1S$-состояние) и $\Delta E^{hfs}(2S)=6.2804$ meV ($2S$-состояние) можно использовать для сравнения с будущими экспериментальными данными коллаборации CREMA. Интервал сверхтонкой структуры $\Delta_{12}=8\Delta E^{hfs}(2S)- \Delta E^{hfs}(1S)=-0.0379$ meV можно использовать для прецизионной проверки квантовой электродинамики.
Рождение $D$-мезонов на Большом адронном коллайдере в реджевском пределе КХД
Authors: Карпишков Антон Витальевич , Karpishkov Anton Vitalievich , Нефедов Максим Александрович , Nefedov Maxim Aleksandrovich , Салеев Владимир Анатольевич , Saleev Vladimir Anatolievich , Шипилова Александра Викторовна , Shipilova Alexandra Viktorovna
Published: November 2015

В работе рассматривается инклюзивное рождение очарованных $D^{0}$, $D^{+}$, $D^{\star+}$ и $D_{s}^{+}$ мезонов в протон-антипротонных соударениях на коллайдере Тэватрон и протон-протонных соударениях на Большом адронном коллайдере (БАК). Теоретические расчeты проведены в лидирующем порядке теории реджезованных партонов (ТРП), основанной на эффективной квантовой теории поля Л. Н. Липатова и подходе $k_{T}$-факторизации при высоких энергиях. В работе были использованы универсальные функции фрагментации (ФФ), полученные фитированием данных рождения $D$-мезонов на линейном электрон-позитронном коллайдере LEP1. Нами описаны распределения $D$-мезонов по поперечному импульсу, измеренные в центральной области быстрот коллаборациями CDF на Тэватроне ($|y|<1$) и ALICE на БАК ($|y|<0.5$) в пределах ошибок измерений и без привлечения свободных параметров. На стадии численных расчeтов нами использовались неинтегрированные глюонные функции распределения (ФР) Кимбера, Мартина и Рыскина (КМР).