bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B12: CLPTM1L and GRP78 interact and promote pancreatic tumor survival under ER-stress and chemoresistance through cell-surface translocation and interaction with PI3K
Authors: James Michael
Published: December 2016

Altered regulation of endoplasmic reticulum (ER) homeostasis has been implicated in many cancers and has recently become a therapeutic and chemosensitization target of interest. Tumor cells must endure ER stress caused by microenvironmental, oxidative, energetic, and therapeutic stresses to survive. However, the role of ER stress survival signaling in pancreatic tumorigenesis has not been elucidated. We have identified Cleft Lip and Palate Transmembrane 1-Like (CLPTM1L)/Cisplatin Resistance Related Protein 9 (CRR9) as an ER stress related target in pancreatic cancer. We recently demonstrated that CRR9/CLPTM1L is overexpressed in 90% of pancreatic ductal adenocarcinomas and associated with poor outcome, while it is not expressed in normal pancreatic ductal epithelium. Furthermore, we have shown that CLPTM1L can confer resistance to chemotherapeutic killing, apoptosis, and anoikis, and is critical for KRas transformation and tumorigenesis. Here, we demonstrate that CLPTM1L interacts with phosphoinositol-3-kinase (PI3K) and the ER stress protein Glucose Related Protein 78 (GRP78) at the tumor cell surface and causes up-regulation of Bcl-xL and pAkt survival signaling. Surface accumulation of both CLPTM1L and GRP78 are induced by ER stress and by chemotherapy in vitro. Subsequent to our recent discovery of the presence of CLPTM1L at the cell surface, we have developed antibody inhibitors of CLPTM1L, which deplete chemotherapy-inducible surface accumulation of CLPTM1L and GRP78, as well as downstream survival signaling through the Akt pathway and Bcl-xL expression. These agents have shown striking anti-tumorigenic efficacy in preclinical models of pancreatic cancer and present a promising therapeutic and chemosensitization approach.

Citation Format: Michael James.{Authors}. CLPTM1L and GRP78 interact and promote pancreatic tumor survival under ER-stress and chemoresistance through cell-surface translocation and interaction with PI3K. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B12.
Abstract B34: A Novel MIF-driven Signaling Drives Disease Aggressiveness by Targeting NR3C2 in Pancreatic Cancer
Authors: Yang Shouhui , He Peijun , Wang Jian , Schetter Aaron , Tang Wei , Funamizu Naotake , Yanaga Katsuhiko , Uwagawa Tadashi , Satoskar Abhay R. , Gaedcke Jochen , Bernhardt Markus , Ghadimi B. Michael , Gaida Matthias M. , Bergmann Frank , Werner Jens , Ried Thomas , Hanna Nader , Alexander H. Richard , Hussain S. Perwez
Published: December 2016

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Pancreatic tumors with aberrant expression of macrophage migration inhibitory factor (MIF) are highly aggressive, and an increased MIF predicts poorer patient survival. We analyzed the expression of coding and non-coding genes in high and low MIF-expressing tumors in multiple cohorts of PDAC patients to identify key signaling pathways that drive disease aggressiveness in tumors with high MIF expression. The identified key genes and pathways were linked to patients’ survival and were mechanistically, functionally and clinically characterized using cell lines, genetically engineered mouse model and PDAC patient cohorts. Here, we report mechanistic, functional and clinical evidence of a novel MIF-driven signaling pathway that inhibits a previously undescribed tumor suppressor, nuclear-receptor-subfamily-3, group-C, member-2 (NR3C2), leading to enhanced disease aggressiveness and poorer survival in PDAC. MIF upregulated miR-301b, which then targeted and suppressed NR3C2 expression. Tumors with high MIF expression showed an elevated miR-301b and a reduced NR3C2 expression. Additionally, patients with a lower NR3C2 expression in tumors showed poorer survival in multiple independent cohorts of PDAC patients. NR3C2 inhibited epithelial-to-mesenchymal transition and enhanced sensitivity to chemotherapeutic drug gemcitabine. Furthermore, genetic deletion of MIF disrupted MIF-mir-301b-NR3C2 axis, which resulted in reduced metastasis and prolonged survival in genetically engineered mouse model of PDAC. These findings provide proof-of-principle that therapies targeting MIF-miR-301b-NR3C2 axis may improve disease outcome in PDAC

Citation Format: Shouhui Yang, Peijun He, Jian Wang, Aaron Schetter, Wei Tang, Naotake Funamizu, Katsuhiko Yanaga, Tadashi Uwagawa, Abhay R. Satoskar, Jochen Gaedcke, Markus Bernhardt, B. Michael Ghadimi, Matthias M. Gaida, Frank Bergmann, Jens Werner, Thomas Ried, Nader Hanna, H. Richard Alexander, S. Perwez Hussain.{Authors}. A Novel MIF-driven Signaling Drives Disease Aggressiveness by Targeting NR3C2 in Pancreatic Cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B34.
Abstract IA10: Biomarker selected therapy for pancreas ductal adenocarcinoma: an emerging reality?
Authors: O'Reilly Eileen M.
Published: December 2016

Pancreas adenocarcinoma remains a major challenge hallmarked by several notables, including a rising incidence, modest effectiveness of current state-of-the-art therapies and a dearth of validated biomarkers for clinical decision making. With regard to germline genomics, about 5-8% of pancreas adenocarcinoma patients will harbor a mutation in BRCA2, BRCA1 and PALB2. These mutations amongst others lead to impaired DNA repair and are identified to be important biomarkers of genomic instability as well as of response to DNA damaging agents. Genomic instability, a result of deleterious mutations of genes functioning in homologous repair mediated DNA repair pathways, yields an exceptional vulnerability in cancer cells named synthetic lethality. Recent studies have elucidated that platinum agents and Poly-ADP-ribose polymerase (PARP) inhibitors may be effective to induce tumor regression in solid tumors bearing an unstable genome including pancreatic cancer. The impact of somatic BRCA mutations on response to DNA targeting agents is currently being investigated. A recent whole genome sequencing study by Waddell et al reported overlapping features in both somatic and germline mutations such as unstable genome along with possible DNA targeting agent sensitivity in both groups. This suggests that gained mutation of DNA repair genes throughout the oncogenesis process may also create synthetic lethality and a larger subset of patients may benefit from these evolving treatment approaches. The characteristics of genomic instability in pancreatic cancer along with its clinical implications and the utility of DNA targeting agents particularly PARP inhibitors as novel treatment approaches will be discussed.

Citation Format: Eileen M. O’Reilly.{Authors}. Biomarker selected therapy for pancreas ductal adenocarcinoma: an emerging reality? [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr IA10.
Abstract IA11: Pancreatic cancer biology and medicine
Authors: Tuveson David
Published: December 2016

Pancreatic cancer remains the most deadly of the common malignancies. To increase our basic understanding of this disease and advance medical approaches, we have recently co-developed with Hans Clevers mouse and human organoid model systems. Our organoid cultures representative of either normal or neoplastic ductal cells facilitate the systematic analysis of neoplastic biochemical cascades, provide a platform to explore therapeutic and diagnostic strategies, and also enable the reconstitution of tumor microenvironment interactions. We have found that Nrf2, a principal regulator of redox metabolism, promotes proliferation in KRAS mutant pancreatic ductal cells in part by regulating the reduced state of the cellular proteome. As a consequence of proteome oxidation, central pathways of homeostasis are impaired, including protein translation. The genes with markedly impaired translation include a number of critical proto-oncogenes. Additionally, diagnostic and therapeutic approaches have revealed new avenues to explore for early detection and disease treatment. Finally, the co-culture of organoids with pancreatic stellate cells promotes the activation of each cell type and results in the production of extracellular matrix. Co-cultures reveal distinct subtypes of stellate cells and provide an opportunity to identify and target novel mediators of the tumor microenvironment.

Citation Format: David Tuveson.{Authors}. Pancreatic cancer biology and medicine. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr IA11.
More than an anticoagulant: Do heparins have direct anti-inflammatory effects?
Authors: Poterucha Timothy J. , Libby Peter , Goldhaber Samuel Z.
Published: December 2016

The heparins, well-known for their anticoagulant properties, may also have anti-inflammatory effects that could contribute to their effectiveness in the treatment of venous thromboembolism and other vascular diseases. This review focuses on the inflammatory pathophysiology that underlies the development of thrombosis and the putative effects of heparin on these pathways. We present evidence supporting the use of heparin for other indications, including autoimmune disease, malignancy, and disseminated intravascular coagulation. These considerations highlight the need for further research to elucidate the mechanisms of the possible pleiotropic effects of the heparins, with a view to advancing treatments based upon heparin derivatives.
Interstitial Fibrosis, Functional Status, and Outcomes in Heart Failure With Preserved Ejection Fraction
Authors: Duca Franz , Kammerlander Andreas A. , Zotter-Tufaro Caroline , Aschauer Stefan , Schwaiger Marianne L. , Marzluf Beatrice A. , Bonderman Diana , Mascherbauer Julia
Published: December 2016

Background—

Myocardial extracellular volume (ECV) accumulation is one of the key pathophysiologic features of heart failure with preserved ejection fraction (HFpEF). Our aims were to (1) measure ECV by cardiac magnetic resonance T1 mapping using the modified Look-Locker inversion recovery (MOLLI) sequence, (2) validate MOLLI-ECV against histology, and (3) investigate the relationship between MOLLI-ECV and prognosis in HFpEF.

Methods and Results—

One-hundred seventeen consecutive HFpEF patients underwent cardiac magnetic resonance imaging, coronary angiography, and invasive hemodynamic assessments at baseline. Eighteen patients also underwent left ventricular biopsy for histological analysis (Histo-ECV). To assess the prognostic impact of MOLLI-ECV, its association with hospitalization for heart failure/cardiac death was tested by multivariable Cox regression analysis. Histo-ECV was 30.1±4.6% and was significantly correlated with MOLLI-ECV (
R
=0.494,
P
=0.037). Patients were followed for 24.0 months (6.0–32.0 months), during which 34 had a cardiac event. By Kaplan–Meier analysis, patients with MOLLI-ECV ≥ the median (28.9%) had shorter event-free survival (log-rank,
P
=0.028). MOLLI-ECV significantly correlated with N-terminal prohormone of brain natriuretic peptide (
P
<0.001), 6-minute walk distance (
P
=0.004), New York Heart Association functional class (
P
=0.009), right atrial pressure (
P
=0.037), and stroke volume (
P
=0.043). By multivariable Cox regression analysis, MOLLI-ECV was associated with outcome among imaging variables (
P
=0.038) but not after adjustment for clinical and invasive hemodynamic parameters.

Conclusions—

We demonstrate that MOLLI-ECV in HFpEF accurately reflects histological ECV, correlates with markers of disease severity, and is associated with outcome among cardiac magnetic resonance parameters but not after adjustment for important clinical and invasive hemodynamic parameters. Nevertheless, MOLLI-ECV has the potential of becoming an important biomarker in HFpEF.
VEGF
165
b Modulates Endothelial VEGFR1–STAT3 Signaling Pathway and Angiogenesis in Human and Experimental Peripheral Arterial Disease
Authors: Ganta Vijay Chaitanya , Choi Min , Kutateladze Anna , Annex Brian H.
Published: December 2016

Rationale:

Atherosclerotic-arterial occlusions decrease tissue perfusion causing ischemia to lower limbs in patients with peripheral arterial disease (PAD). Ischemia in muscle induces an angiogenic response, but the magnitude of this response is frequently inadequate to meet tissue perfusion requirements. Alternate splicing in the exon-8 of vascular endothelial growth factor (VEGF)-A results in production of proangiogenic VEGF
xxx
a isoforms (VEGF
165
a, 165 for the 165 amino acid product) and antiangiogenic VEGF
xxx
b (VEGF
165
b) isoforms.

Objective:

The antiangiogenic VEGF
xxx
b isoforms are thought to antagonize VEGF
xxx
a isoforms and decrease activation of VEGF receptor-2 (VEGFR2), hereunto considered the dominant receptor in postnatal angiogenesis in PAD. Our data will show that VEGF
165
b inhibits VEGFR1 signal transducer and activator of transcription (STAT)-3 signaling to decrease angiogenesis in human and experimental PAD.

Methods and Results:

In human PAD versus control muscle biopsies, VEGF
165
b: (1) is elevated, (2) is bound higher (versus VEGF
165
a) to VEGFR1 not VEGFR2, and (3) levels correlated with decreased VEGFR1, not VEGFR2, activation. In experimental PAD, delivery of an isoform-specific monoclonal antibody to VEGF
165
b versus control antibody enhanced perfusion in animal model of severe PAD (Balb/c strain) without activating VEGFR2 signaling but with increased VEGFR1 activation. Receptor pull-down experiments demonstrate that VEGF
165
b inhibition versus control increased VEGFR1–STAT3 binding and STAT3 activation, independent of Janus-activated kinase-1)/Janus-activated kinase-2. Using VEGFR1
+/−
mice that could not increase VEGFR1 after ischemia, we confirm that VEGF
165
b decreases VEGFR1–STAT3 signaling to decrease perfusion.

Conclusions:

Our results indicate that VEGF
165
b prevents activation of VEGFR1–STAT3 signaling by VEGF
165
a and hence inhibits angiogenesis and perfusion recovery in PAD muscle.
From the Bataclan to Nice
Authors: Boutin Bérénice , Paulussen Christophe
Published: December 2016

This policy brief analyses the state of emergency regime that was declared by the French Government immediately after the November 2015 attacks and ties it to France’s legislative response to terrorism more generally. It is observed that, at various levels, serious human rights concerns arise that are detrimental to the fight against terrorism. In conclusion, concrete policy recommendations are offered to address these concerns.
Enhancing International Cyber Security
Authors: van der Meer Sico
Published: December 2016

Cyber aggression is an increasing threat to international security and stability. While national policies intended to deter cyber aggression may offer some solution in the short term, their effects in the long term are doubtful. National cyber-deterrence policies entail the risk of an on-going cyber arms race and a cycle of escalation between potential cyber opponents. Diplomacy may offer fewer results in the short term, but it is more promising in the long term. Confidence-building measures and international norms and values may not be easy to reach, but in the end they could be more effective (and cheaper) than a single focus on national cyber-deterrence strategies. In the long term, cooperation between states to establish confidence and commonly accepted norms of behaviour in cyber space are the most promising ways available to achieve enduring cyber security and stability. Enhancing interstate co-operation, transparency and predictability of behaviour in cyberspace will reduce the risks of misperception, escalation and conflict.
The Role of Human Rights in Long-Term Sentencing
Authors: Liem Marieke , Elbers Jan Maarten
Published: December 2016

In recent decades, the number of long-term detainees held worldwide has increased significantly. Academics and policy makers have begun to challenge the widespread use and effectiveness of such severe sentences, however. This article aims to shed light on the role of human rights in imposing and executing long-term custodial sentences. There appears to be tension between ensuring that human rights are respected and provision of security through the incapacitation of offenders. This tension can only be understood properly in the context of contemporary risk-management associated with increased punitiveness.
Revision of Diplosynapsis Enderlein, 1914 (Diptera, Asilidae, Asilinae) with description of four new species
Authors: VIEIRA RODRIGO , RAFAEL JOSÉ ALBERTINO
Published: December 2016

The robber fly genus Diplosynapsis Enderlein, 1914 is reviewed and four new species are described—D. chela sp. nov. (Amazonas state, Brazil), D. fisheri sp. nov. (Guapiles, Heredia, Limon, Puntarenas province, Costa Rica), D. spina sp. nov. (Rio de Janeiro state, Brazil) and D. uncinata sp. nov. (Amazonas state, Brazil). A lectotype is designated for D. cellata (Schiner, 1868) pres. desig. and comments are made on D. remus Tomasovic, 2002. An identification key and illustrations are presented for all species.
Determinants and taxonomic consequences of extreme egg shell variability in Ramazzottius subanomalus (Biserov, 1985) (Tardigrada)
Authors: STEC DANIEL , MOREK WITOLD , GĄSIOREK PIOTR , KACZMAREK ŁUKASZ , MICHALCZYK ŁUKASZ
Published: December 2016

Nearly a half of known eutardigrade species lay ornamented eggs. The ornamentation is thought to provide attachment of the egg to the substrate and protection for the developing embryo, but from the taxonomic point of view chorion morphology may also provide key characters for species differentiation and identification, especially between closely related taxa. Nonetheless, despite the evolutionary and taxonomic importance of the egg shell, the determinants of its morphology are very poorly, if at all, understood. Here, we combine morphological, molecular and experimental approaches in an attempt to separate the genetic and environmental factors that shape egg chorion morphology in Ramazzottius subanomalus (Biserov, 1985). Our integrative study, based on a population of R. subanomalus isolated from a single moss sample, revealed (1) remarkable variation in egg shell morphology, but (2) relatively little variation in animal morphometric traits, and (3) genetic differentiation, expressed as two ITS-2 haplotypes, but no parallel polymorphism in COI. Although animals did not differ morphometrically between the haplotypes, eggs laid by haplotype 1 and 2 females exhibited highly statistically significant differences in all measured traits. The study demonstrates, for the first time, a correlation between phenotypic and genetic variability within a tardigrade species. The revealed congruence between genetic and morphological traits might be viewed as an example of incipient speciation that illustrates early evolutionary steps leading to species complexes that differ primarily in terms of egg shell morphology. Moreover, our data confirm the value of the ITS-2 fragment in distinguishing very closely related tardigrade lineages.
A Comprehensive Database of Flood Events in the Contiguous United States from 2002 to 2013
Authors: Shen Xinyi , Mei Yiwen , Anagnostou Emmanouil N.
Published: December 2016

Notwithstanding the rich record of hydrometric observations compiled by the U.S. Geological Survey (USGS) across the contiguous United States (CONUS), flood event catalogs are sparse and incomplete. Available databases or inventories are mostly survey- or report-based, impact oriented, or limited to flash floods. These data do not represent the full range of flood events occurring in CONUS in terms of geographical locations, severity, triggering weather, or basin morphometry. This study describes a comprehensive dataset consisting of more than half a million flood events extracted from 6,301 USGS flow records and radar-rainfall fields from 2002 to 2013, using the characteristic point method. The database features event duration; first- (mass center) and second- (spreading) order moments of both precipitation and flow, flow peak and percentile, event runoff coefficient, base flow, and information on the basin geomorphology. It can support flood modeling, geomorphological and geophysical impact studies, and instantaneous unit hydrograph and risk analyses, among other investigations. Preliminary data analysis conducted in this study shows that the spatial pattern of flood events affected by snowmelt correlates well with the mean annual snowfall accumulation pattern across CONUS, the basin morphometry affects the number of flood events and peak flows, and the concentration time and spreadness of the flood events can be related to the precipitation first- and second-order moments.
Condensational Growth of Drops Formed on Giant Sea-Salt Aerosol Particles
Authors: Jensen Jørgen B. , Nugent Alison D.
Published: December 2016

The most basic aspect of cloud formation is condensational growth onto cloud condensation nuclei (CCN). As such, condensational growth of cloud drops is often assumed to be a well-understood process described by the drop growth equation. When this process is represented in models, CCN activate into cloud drops at cloud base, and it is often assumed that drops consist of pure water or that the hygroscopic contribution after drop activation is small because of the inclusion of only small CCN. Drop growth rate in adiabatic ascent in such models is proportional to supersaturation and assumed to be inversely proportional to the drop radius, thereby making the drop spectrum narrow with altitude. However, the present study demonstrates that drop growth on giant sea-salt aerosol particles (GCCN; dry radius 0.5 m) behaves differently. For typical marine stratocumulus updrafts and for drops grown on GCCN with sizes m, these drops typically remain concentrated salt solutions. Because of this, their condensational growth is accelerated, and they rapidly attain precipitation drop sizes through condensation only. Additionally, drops formed on GCCN may also grow by condensation in cloudy downdrafts. The strong effect of condensation on GCCN is important when carried through to calculating rain-rate contribution as a function of aerosol size. GCCN larger than 2 m account for most of the rainfall rate in the modeled precipitating marine stratocumulus.
Reduction of the Entrainment Velocity by Cloud Droplet Sedimentation in Stratocumulus
Authors: de Lozar Alberto , Mellado Juan Pedro
Published: December 2016

The effect of sedimentation on stratocumulus entrainment is investigated using direct numerical simulations of a cloud-top mixing layer driven by radiative and evaporative cooling. The simulations focus on the meter and submeter scales that are expected to be relevant for entrainment, and the finest grid spacing is Δx = 26 cm. The entrainment velocity is investigated from the analysis of the integrated-buoyancy evolution equation, which is exactly derived from the flow evolution equations. The analysis shows that sedimentation interacts with entrainment through two different mechanisms. As previously reported, sedimentation prevents droplets from evaporating in the entrainment zone, which in turn reduces the entrainment velocity. Here it is shown that sedimentation also promotes a positive buoyancy flux that directly opposes entrainment. The strengths of both mechanisms are characterized by two different settling numbers, which allow for predicting which meteorological conditions favor the reduction of entrainment by sedimentation. These new insights allow for including sedimentation in a parameterization of the entrainment velocity. The reduction of the entrainment velocity by sedimentation predicted by the parameterization and observed in the simulations is 3 times larger than previously reported in large-eddy simulations, which implies that meter- and submeter-scale turbulence plays an important role in the interaction of entrainment with sedimentation. On the whole, analysis and simulations indicate that stratocumulus entrainment is more sensitive to the cloud droplet number density due to sedimentation than previously thought.
Pathways of Meltwater Export from Petermann Glacier, Greenland
Authors: Heuzé Céline , Wåhlin Anna , Johnson Helen L. , Münchow Andreas
Published: December 2016

Intrusions of Atlantic Water cause basal melting of Greenland’s marine-terminating glaciers and ice shelves, such as that of Petermann Glacier, in northwest Greenland. The fate of the resulting glacial meltwater is largely unknown. It is investigated here, using hydrographic observations collected during a research cruise in Petermann Fjord and adjacent Nares Strait onboard icebreaker (I/B) Oden in August 2015. A three end-member mixing method provides the concentration of Petermann ice shelf meltwater. Meltwater from Petermann is found in all of the casts in adjacent Nares Strait, with the highest concentration along the Greenland coast in the direction of Kelvin wave phase propagation. The meltwater from Petermann mostly flows out on the northeast side of the fjord as a baroclinic boundary current, with the depth of maximum meltwater concentrations approximately 150 m and shoaling along its pathway. At the outer sill, which separates the fjord from the ambient ocean, approximately 0.3 mSv (1 Sv ≡ 106 m3 s−1) of basal meltwater leaves the fjord at depths between 100 and 300 m. The total geostrophic heat and freshwater fluxes close to the glacier’s terminus in August 2015 were similar to those estimated in August 2009, before the two major calving events that reduced the length of Petermann’s ice tongue by nearly a third and despite warmer inflowing Atlantic Water. These results provide a baseline but also highlight what is needed to assess properly the impact on ocean circulation and sea level of Greenland’s mass loss as the Atlantic Water warms up.
Doppler Correction of Wave Frequency Spectra Measured by Underway Vessels
Authors: Collins C. O. , Blomquist B. , Persson O. , Lund B. , Rogers W. E. , Thomson J. , Wang D. , Smith M. , Doble M. , Wadhams P. , Kohout A. , Fairall C. , Graber H. C.
Published: December 2016

“Sea State and Boundary Layer Physics of the Emerging Arctic Ocean” is an ongoing Departmental Research Initiative sponsored by the Office of Naval Research (http://www.apl.washington.edu/project/project.php?id=arctic_sea_state). The field component took place in the fall of 2015 within the Beaufort and Chukchi Seas and involved the deployment of a number of wave instruments, including a downward-looking Riegl laser rangefinder mounted on the foremast of the R/V Sikuliaq. Although time series measurements on a stationary vessel are thought to be accurate, an underway vessel introduces a Doppler shift to the observed wave spectrum. This Doppler shift is a function of the wavenumber vector and the velocity vector of the vessel. Of all the possible relative angles between wave direction and vessel heading, there are two main scenarios: 1) vessel steaming into waves and 2) vessel steaming with waves. Previous studies have considered only a subset of cases, and all were in scenario 1. This was likely to avoid ambiguities, which arise when the vessel is steaming with waves. This study addresses the ambiguities and analyzes arbitrary cases. In addition, a practical method is provided that is useful in situations when the vessel is changing speed or heading. These methods improved the laser rangefinder estimates of spectral shapes and peak parameters when compared to nearby buoys and a spectral wave model.
Endovascular Repair of Type IIIb Endoleak With the Amplatzer Septal Occluder
Authors: McWilliams Richard G. , Chan Tze Yuan , Smout Jonathan , Torella Francesco , Fisher Robert K.
Published: December 2016

Purpose: To report the successful treatment of a type IIIb endoleak with an Amplatzer Septal Occluder. Case Report: A 76-year-old man was found to have a type IIIb endoleak in the proximal body component of a fenestrated graft at 4-year surveillance imaging; the leak was associated with rapid aneurysm growth. The anatomy of the graft and position of the fabric defect precluded treatment by relining with a secondary endograft. The defect was demonstrated with catheter angiography, sized with an angioplasty balloon, and repaired using an Amplatzer Septal Occluder. Follow-up imaging at 6 months showed no endoleak and marked reduction in the aneurysm size. Conclusion: The Amplatzer Septal Occluder may be considered as an option for managing type IIIb endoleaks.
Targeting the Opioid Pathway for Uremic Pruritus
Authors: Jaiswal Deep , Uzans Drea , Hayden Jill , Kiberd Bryce A. , Tennankore Karthik K.
Published: December 2016

Background:

Patients undergoing hemodialysis or peritoneal dialysis often experience pruritus which is associated with morbidity and mortality. One proposed treatment approach is to target the opioid pathway using either µ-opioid antagonists or κ-opioid agonists.

Objective:

To review the efficacy of targeting the opioid pathway for pruritus among dialysis patients (uremic pruritus).

Design:

Systematic review and meta-analysis.

Setting/Methods:

The systematic review included randomized controlled and randomized crossover trials identified in the MEDLINE, EMBASE, and Cochrane databases (1990 to June 2014) evaluating the efficacy of µ-opioid antagonists or κ-opioid agonists in the treatment of uremic pruritus.

Patients:

Adult (≥18 years) chronic dialysis patients.

Measurements:

The primary outcome being evaluated was reduction in itch severity measured on a patient-reported visual analog scale (VAS).

Results:

Five studies out of 3587 screened articles met the inclusion criteria. Three studies evaluated the efficacy of naltrexone, a µ-opioid antagonist, and 2 studies evaluated the efficacy of nalfurafine, a κ-opioid agonist. Duration of included studies was short, ranging from 2 to 9 weeks.

Limitations:

Due to the heterogeneity in reporting of outcomes, data from the studies evaluating naltrexone could not be pooled. Pooled analysis, using a random effects model, found that use of nalfurafine resulted in a 9.50 mm (95% confidence interval [CI], 6.27-12.74, P < .001) greater reduction of itch severity (measured on a 100-mm VAS) than placebo in the treatment of uremic pruritus.

Conclusions:

Nalfurafine holds some promise with respect to the treatment of uremic pruritus among dialysis patients. However, more long-term randomized controlled trials evaluating the efficacy of therapies targeting the opioid pathway for uremic pruritus are required.
The Hypothalamic–Pituitary–Adrenal Axis and Anesthetics: A Review
Authors: Besnier Emmanuel , Clavier Thomas , Compere Vincent
Published: December 2016

The hypothalamic–pituitary–adrenal (HPA) axis is essential for human adaptation to stress. However, many anesthetic agents may interfere with the activity of this axis. Although etomidate is known for its suppressive effect on HPA axis function, in vitro evidence suggests that many other drugs used in anesthesia care may also interfere with HPA activity. In this review, we discuss the mechanisms by which all HPA axis activity may be altered during anesthesia and critical care and focus on the impact of hypnotic and analgesic drugs.
The Geographic Distribution of Pediatric Anesthesiologists Relative to the US Pediatric Population
Authors: Muffly Matthew K. , Medeiros David , Muffly Tyler M. , Singleton Mark A. , Honkanen Anita
Published: December 2016

BACKGROUND:

The geographic relationship between pediatric anesthesiologists and the pediatric population has potentially important clinical and policy implications. In the current study, we describe the geographic distribution of pediatric anesthesiologists relative to the US pediatric population (0–17 years) and a subset of the pediatric population (0–4 years).

METHODS:

The percentage of the US pediatric population that lives within different driving distances to the nearest pediatric anesthesiologist (0 to 25 miles, >25 to 50 miles, >50 to 100 miles, >100 to 250 miles, and >250 miles) was determined by creating concentric driving distance service areas surrounding pediatric anesthesiologist practice locations. US Census block groups were used to determine the sum pediatric population in each anesthesiologist driving distance service area. The pediatric anesthesiologist-to-pediatric population ratio was then determined for each of the 306 hospital referral regions (HRRs) in the United States and compared with ratios of other physician groups to the pediatric population. All geographic mapping and analysis was performed using ArcGIS Desktop 10.2.2 mapping software (Redlands, CA).

RESULTS:

A majority of the pediatric population (71.4%) lives within a 25-mile drive of a pediatric anesthesiologist; however, 10.2 million US children (0–17 years) live greater than 50 miles from the nearest pediatric anesthesiologist. More than 2.7 million children ages 0 to 4 years live greater than 50 miles from the nearest identified pediatric anesthesiologist. The median ratio of pediatric anesthesiologists to 100,000 pediatric population at the HRR level was 2.25 (interquartile range, 0–5.46). Pediatric anesthesiologist geographic distribution relative to the pediatric population by HRR is lower and less uniform than for all anesthesiologists, neonatologists, and pediatricians.

CONCLUSIONS:

A substantial proportion of the US pediatric population lives greater than 50 miles from the nearest pediatric anesthesiologist, and pediatric anesthesiologist-to-pediatric population ratios by HRR vary widely across the United States. These findings are important given that the new guidelines from the American College of Surgeons Children’s Surgery Verification™ Quality Improvement Program state that pediatric anesthesiologists must care for a subset of pediatric patients. Because of the geographic distribution of pediatric anesthesiologists relative to the pediatric population, access to care by a pediatric anesthesiologist may not be feasible for all children, particularly for those with limited resources or in emergent situations.
Redox Properties of Copper(I) Complex Bearing 4,7-Diphenyl-2,9-dimethyl-1,10-phenanthroline and 1,4-Bis(diphenylphosphino)butane Ligands and Effects of Light in the Presence of Chloroform
Authors: Nishikawa Michihiro , Kakizoe Daichi , Saito Yuma , Ohishi Tomoyuki , Tsubomura Taro
Published: December 2016

We have examined emission and redox properties of a copper(I) complex bearing a phenanthroline type ligand and the 1,4-bis(diphenylphosphino)butane ligand. Changes in the absorption spectra upon electrolysis and light irradiation in the presence of chloroform indicate the formation of bis(diimine)copper(I) complexes.
The conserved SNARE SEC-22 localizes to late endosomes and negatively regulates RNA interference in Caenorhabditis elegans
Authors: Zhao Yani , Holmgren Benjamin T. , Hinas Andrea
Published: December 2016

Small RNA pathways, including RNA interference (RNAi), play crucial roles in regulation of gene expression. Initially considered to be cytoplasmic, these processes have later been demonstrated to associate with membranes. For example, maturation of late endosomes/multivesicular bodies (MVBs) is required for efficient RNAi, whereas fusion of MVBs to lysosomes appears to reduce silencing efficiency. SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) mediate membrane fusion and are thus at the core of membrane trafficking. In spite of this, no SNARE has previously been reported to affect RNAi. Here, we demonstrate that in Caenorhabditis elegans, loss of the conserved SNARE SEC-22 results in enhanced RNAi upon ingestion of double-stranded RNA. Furthermore, SEC-22 overexpression inhibits RNAi in wild-type animals. We find that overexpression of SEC-22 in the target tissue (body wall muscle) strongly suppresses the sec-22(−) enhanced RNAi phenotype, supporting a primary role for SEC-22 in import of RNAi silencing signals or cell autonomous RNAi. A functional mCherry::SEC-22 protein localizes primarily to late endosomes/MVBs and these compartments are enlarged in animals lacking sec-22. SEC-22 interacts with late endosome-associated RNA transport protein SID-5 in a yeast two-hybrid assay and functions in a sid-5-dependent manner. Taken together, our data indicate that SEC-22 reduces RNAi efficiency by affecting late endosome/MVB function, for example, by promoting fusion between late endosomes/MVBs and lysosomes. To our knowledge, this is the first report of a SNARE with a function in small RNA-mediated gene silencing.
Highlights from the ISCB Student Council Symposia in 2016
Authors: Cuypers Bart , Jacobsen Annika , Siranosian Ben , Schwahn Kevin , Conard Ashley Mae , Aben Nanne , Hassan Mehedi , Fatima Nazeefa , Hermans Susanne M.A. , Woghiren Melissa , Meysman Pieter , Rahman Farzana , Jigisha Anupama
Published: December 2016

This editorial provides a brief overview of the 12th International Society for Computational Biology (ISCB) Student Council Symposium and the 4th European Student Council Symposium held in Florida, USA and The Hague, Netherlands, respectively. Further, the role of the ISCB Student Council in promoting education and networking in the field of computational biology is also highlighted.
Effects of tranexamic acid on platelet function and thrombin generation (ETAPlaT): WOMAN trial sub-study
Authors: Dallaku Kastriot , Shakur Haleema , Roberts Ian , Edwards Phil , Beaumont Danielle , Delius Maria , Siegmund Braun , Gliozheni Orion , Tasha Ilir , Cenameri Saimir , Mansmann Ulrich
Published: December 2016

Background. Postpartum haemorrhage (PPH) is a leading cause of maternal death. Tranexamic acid (TXA) has the potential to reduce bleeding and a large randomized placebo controlled trial of its effect in women with PPH (The WOMAN trial) is underway. TXA might also affect coagulation factors and platelets. Objectives. To examine the effect of TXA on thrombin generation, platelet function, fibrinogen, D-dimer and coagulation factors in women with PPH. Methods. We will conduct a sub-study within the WOMAN trial. Women with clinically diagnosed primary PPH after vaginal or caesarean delivery are eligible for inclusion. Blood samples will be collected at baseline and 30 minutes after the first dose of study treatment. Using platelet poor plasma we will measure thrombin generation, fibrinogen, D-dimer, factor V and VIII, and Von Willebrand factor. Platelet function will be evaluated in whole blood using Multiplate® tests.Outcomes. The primary outcome is the effect of TXA on thrombin generation. Secondary outcomes include the effect of TXA on platelet function, fibrinogen, D-dimer and coagulation factors.
IMPROVEMENT OF LEGISLATIVE AND STATUTORY REGULATION OF THE BANK ACTIVITY
Authors: Киризлеева Алиса , Kirizleeva Alisa
Published: December 2016

The article studies the problems of banks solvency during the crisis. It examines the organizational model of control improvement in order to conduct an efficient and independent internal auditing. It also suggests the ways to improve legislative and statutory regulation of the bank activity on the basis of Basel standards.
Current status of the organization, planning, management and development of industrial enterprises using IT
Authors: Кораблев Алексей , Korablev Aleksey , Кулантаев Асланбек , Kulantaev Aslanbek
Published: December 2016

The modern economy is characterized by a high level of turbulence change the vector of both global and regional markets: the crisis, uncertainty, growth. The article deals with the most significant current trends planning organization, management and development of industrial enterprises using information technology as a whole. It reveals the feasibility of establishing a system of governance that would be adaptable to the vector of economic development, the role and prospects of development of management information systems themselves.
Comportamento de cópula em Cyclocephala verticalis Burmeister (Coleoptera: Scarabaeidae)
Authors: Barbosa Carlos Aparecido Ferreira , Rodrigues Sérgio Roberto
Published: December 2016

O gênero Cyclocephala possui grande quantidade de espécies distribuídas nas várias regiões do Brasil, entretanto, poucos são os estudos relacionados ao comportamento de cópula, assim o presente trabalho teve como objetivo estudar o comportamento de cópula de Cyclocephala verticalis Burmeister. Com uma armadilha luminosa instalada ao lado de área de pastagens, foram realizadas coletas de adultos de agosto a setembro de 2013. Em laboratório machos e fêmeas foram mantidos em recipientes separados e ao anoitecer, foram formados casais para observações das etapas que envolvem o comportamento de cópula. De 28 de outubro a 4 de novembro de 2013, para determinar o horário de voo, recolheu-se os insetos coletados na armadilha luminosa a cada 60 min, iniciando os estudos as 18:00 h e encerrando as observações as 6:00 h do dia seguinte. Ao saírem do solo os adultos realizaram ativamente o voo, em seguida pousaram, e o macho ao localizar a fêmea, se aproxima e a toca com o primeiro par de pernas e antenas. Se a fêmea aceita o macho, ocorre à cópula a qual durou 12,5 + 1,3 min em média, e ocorreu entre 19:00 h e 02:00 h. Em algumas ocasiões as fêmeas não aceitaram os machos para a cópula, indicando que os estes provavelmente não estavam aptos a se reproduzirem, ou a própria fêmea não estava apta a se reproduzir, havendo nesse momento reconhecimento químico entre os adultos para a formação do casal. Os adultos revoaram em campo em maiores quantidades das 20:00 h as 23:00 h.Mating Behavior in Cyclocephala verticalis Burmeister (Coleoptera: Scarabaeidae)Abstract. The genus Cyclocephala has a large number of species distributed in various regions of Brazil, however, there are few studies related to mating behavior of this group, so this paper was to study the behavior of copulation Cyclocephala verticalis Burmeister. With a light trap installed next to the pasture area, being performed collections of adults from August to September 2013. In laboratory males and females were kept in separate containers and at dusk, couples have been formed to observations of steps involving the behavior of copula. From October 28 to November 4 of 2013, to determine the time of fly, was collected the insects on the light trap, every 60 minutes, starting the studies the 18:00 pm and closing remarks at 6:00 am, from the following day. Upon leaving the soil adults actively performed the flight then landed, and the male to find the female, approaches and touches it with the first pair of legs and antennae. If the female accepts the male, to copulate occurs which lasted 12.5 + 1.3 min on average, and occurred between 19:00 pm and 02:00 am. Sometimes the females did not accept males for copulation, indicating that these probably were not able to reproduce, or female herself was not able to reproduce, with that time chemical recognition among adults for the formation of the couple. Adults fluttered on the pitch in larger quantities 20:00 pm to 23:00 pm.
Primeiro Registro de Afídeos (Hemiptera: Aphidoidea) em Carambola (Averrhoa carambola L.) no Brasil
Authors: Cunha Suzan Beatriz Zambon da , Sousa e Silva Carlos Roberto
Published: December 2016

A carambola (Averrhoa carambola L.) árvore de origem Asiática foi introduzida no Brasil em 1817, desde então vem aumentando sua área de cultivo no país. A planta é atacada por poucos insetos como as moscas e percevejos. Este trabalho relata a presença de Aphis gossypii Glover em A. carambola pela primeira vez no Brasil.First Record of Aphids (Hemiptera: Aphididae) on Starfruit (Averrhoa carambola L.) in BrazilAbstract. The starfruit (Averrhoa carambola L.) has origin Asiatic and was introduced in Brazil in 1817, since then has increased its cultivation area in the country. The plant is attacked by few insects like flies and bugs. This work reports the presence of Aphis gossypii Glover on A. carambola for the first time in Brazil.
Priva lappulacea (L.) Pers. (Verbenaceae): Nova Hospedeira de Tetranychus gigas Pritchard & Baker (Acari: Tetranychidae) no Brasil
Authors: Santos Rodrigo Souza , Moraes Gilberto José de , Salimena Fátima Regina Gonçalves , Ferreira Cleidiane de Andrade
Published: December 2016

An infestation of Tetranychus gigas (Acari: Tetranychidae) was observed on Priva lappulacea plants in anthropized areas in the municipality of Paraíso do Tocantins, Tocantins state, Brazil. Mites were found in large colonies mainly on the underside of the leaves. This observation confirms P. lappulacea as a new host of T. gigas in Brazil, in addition to confirming the first records of P. lappulacea and T. gigas for Tocantins state.Priva lappulacea (L.) Pers. (Verbenaceae): New Host of Tetranychus gigas Pritchard & Baker (Acari: Tetranychidae) in BrazilResumo. Relata-se a infestação de Tetranychus gigas (Acari: Tetranychidae) em plantas de Priva lappulacea em área antropizada no município de Paraíso do Tocantins, Estado de Tocantins. Os ácaros foram observados em numerosas colônias, principalmente na face inferior das folhas. Após confirmação, registra-se, portanto uma nova planta hospedeira para T. gigas no Brasil, além do primeiro registro de P. lappulacea e de T. gigas para o Estado de Tocantins.
Armadilhas Atrativas como Ferramenta de Amostragem de Vespas Sociais (Hymenoptera: Vespidae): Uma Meta-Análise
Authors: Maciel Tatiane Tagliatti , Barbosa Bruno Corrêa , Prezoto Fábio
Published: December 2016

Dado o reconhecido papel das vespas sociais no equilíbrio dos ecossistemas é clara a importância de estudos sobre a diversidade desses insetos e, para isso, é essencial o uso de um método apropriado. Assim, o objetivo do presente trabalho foi realizar uma análise detalhada dos estudos de diversidade em vespas sociais conduzidos em Minas Gerais avaliando o uso das armadilhas atrativas.Attractive Traps as a Sampling Tool of Social Wasps (Hymenoptera: Vespidae): a Meta-SynthesisAbstract. Studying social wasp diversity, with special concern regarding the chosen study method, is of increasing importance due to the acknowledgement of this group’s role in keeping the balance of ecosystems. The objective of this study, therefore, was to assess the using of bait traps in social wasp diversity studies in the Minas Gerais state, southeastern Brazil.
Industries’ Potential for Interdependency and Profitability: A Panel of 135 Industries, 1988–1996
Authors: Lee Gwendolyn K. , Alnahedh Mishari A.
Published: December 2016

An industry’s potential for interdependency among productive activities is one of the central concepts in strategic management. Although theoretical models have clarified how and why industry average profitability should peak at moderate levels of interdependency, the empirical evidence so far has not supported the inverted-U-shaped relationship. By developing a measure that is based on how frequently pieces of knowledge are used jointly in technological inventions, we find strong support that confirms the predicted relationship between interdependency and industry average profitability. We also find evidence supporting an inverted-U-shaped relationship between interdependency and firm profitability. Moreover, our measure captures how the potential in interdependency may change over time within an industry. The temporal variation allows us to correct omitted variable biases, which poses concerns that weren’t raised in previous studies. The measure is created from more than 1.93 million technological patents that have been approved by the U.S. Patent and Trade Office between 1901 and 1996. Since patent data are available to the public, future studies can readily build on our measure of industries’ potential for interdependency.