bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECTIVE REFRACTORY PERIOD, FULL RECOVERY TIME, AND PREMATURE RESPONSE INTERVAL OF VENTRICULAR MUSCLE IN THE INTACT UNANÆSTHETISED CAT AND RABBIT
Authors: Drury Alan N. 
Published: December 2015

1. In the intact anæsthetised or unanæsthetised cat or rabbit it is possible, by suitable methods, to estimate the refractory period and the time of full recovery of conduction (full recovery time) and the premature response interval of the ventricular muscle.2. The measurements closely agree with those which are obtained in the exposed heart.3. The refractory period proves too variable to be used as a comparative measurement, but the full recovery time and premature response interval show a great constancy from one animal to another of the same species.4. The full recovery time and premature response interval are definitely changed by injection of quinidine or barium, but are undisturbed when the heart is dilated by chloroform.5. The method allows repeated observations of these measurements to be made upon the same animal.
Vasoactive intestinal polypeptide, 5‐hydroxytryptamine and reflex hyperaemia in the small intestine of the cat
Authors: Eklund S. , Fahrenkrug J. , Jodal M. , Lundgren O. , de Muckadell O. B. Schaffalitzky , Sjöqvist A. 
Published: December 2015

1. The release of vasoactive intestinal polypeptide (VIP) into venous blood from the small intestine of the cat was studied when mechanically stimulating the intestinal mucosa and during close intra‐arterial infusions of 5‐hydroxytryptamine (5‐HT) or isopropylnoradrenaline. The studies were performed on anaesthetized cats given atropine.2. Mechanical stimulation of the intestinal mucosa induced a vasodilatation and a release of VIP into the intestinal venous blood. Intra‐arterial administration of tetrodotoxin was given in doses that blocked the vasoconstrictor effect of the regional sympathetic nerve fibres. This also abolished the vascular response and the release of VIP into blood upon mechanical stimulation.3. Close intra‐arterial administration of 2‐bromo‐lysergic acid diethylamide reduced the VIP release and the intestinal vasodilatation upon mucosal stimulation to largely the same extent.4. Close intra‐arterial infusions of 5‐HT produced a marked release of VIP from the intestine and a moderate vasodilatation. Close intra‐arterial infusions of isopropylnoradrenaline, which caused a pronounced intestinal vasodilatation, evoked only a small release of VIP.5. The results are compatible with the hypothesis that the vasodilatation in the gut, induced by mechanical mucosal stimulation, is mediated via an intramural nervous reflex containing a neurone capable of releasing VIP. It is proposed that the nervous reflex is activated by the release of 5‐HT from the enterochromaffin cells evoked by mechanical stimulation of the mucosa.
Primary afferent depolarization in the in vitro frog olfactory bulb
Authors: Jahr C. E. , Nicoll R. A. 
Published: December 2015

1. Experiments on the frog olfactory bulb have been performed in vitro in order to determine whether primary afferent transmission is modified by presynaptic inhibition.2. Stimulation of the olfactory nerve resulted in a prolonged depolarization of the olfactory nerve as recorded across a sucrose gap. Unstimulated olfactory nerve fibres adjacent to the stimulated fibres were also depolarized.3. An excitability increase of the olfactory nerve terminals was found that lasted the entire duration of the olfactory nerve depolarization, indicating that the terminals themselves were depolarized. Both the olfactory nerve depolarization and the excitability increase were blocked by cobalt and manganese ions.4. Low concentrations of glutamate were found to produce a substantial depolarization of the olfactory nerve. Although gamma‐aminobutyric acid (GABA) also elicited a depolarization of the olfactory nerve, picrotoxin, a GABA antagonist, did not reduce the stimulus‐evoked olfactory nerve depolarization.5. Recording with potassium‐sensitive electrodes in the olfactory nerve terminal region demonstrated an increase in extracellular potassium with the same rise time and duration as the olfactory nerve depolarization. Cobalt and manganese blocked the potassium increase and the olfactory nerve depolarization without affecting the presynaptic action potential.6. The focally recorded extracellular current resulting from orthodromic synaptic excitation of the secondary olfactory relay neurones was blocked at short intervals by paired stimulation and decreased for the duration of the olfactory nerve depolarization. This suggests a decreased release of transmitter from the olfactory nerve terminals.7. The possible role of potassium and/or a neurotransmitter in generating the olfactory nerve depolarization and inhibition is discussed.
Contribution of Physical Interactions to Signaling Specificity between a Diguanylate Cyclase and Its Effector
Authors: Dahlstrom Kurt M. , Giglio Krista M. , Collins Alan J. , Sondermann Holger , O’Toole George A. 
Published: December 2015

ABSTRACT

Cyclic diguanylate (c-di-GMP) is a bacterial second messenger that controls multiple cellular processes. c-di-GMP networks have up to dozens of diguanylate cyclases (DGCs) that synthesize c-di-GMP along with many c-di-GMP-responsive target proteins that can bind and respond to this signal. For such networks to have order, a mechanism(s) likely exists that allow DGCs to specifically signal their targets, and it has been suggested that physical interactions might provide such specificity. Our results show a DGC from
Pseudomonas fluorescens
physically interacting with its target protein at a conserved interface, and this interface can be predictive of DGC-target protein interactions. Furthermore, we demonstrate that physical interaction is necessary for the DGC to maximally signal its target. If such “local signaling” is a theme for even a fraction of the DGCs used by bacteria, it becomes possible to posit a model whereby physical interaction allows a DGC to directly signal its target protein, which in turn may help curtail undesired cross talk with other members of the network.

IMPORTANCE
An important question in microbiology is how bacteria make decisions using a signaling network made up of proteins that make, break, and bind the second messenger c-di-GMP, which is responsible for controlling many cellular behaviors. Previous work has shown that a given DGC enzyme will signal for specific cellular outputs, despite making the same diffusible molecule as its sibling DGCs in the unpartitioned space of the bacterial cell. Understanding how one DGC differentiates its output from the dozens of other such enzymes in the cell is synonymous with understanding a large component of the bacterial decision-making machinery. We present evidence for a helix on a DGC used to physically associate with its target protein, which is necessary to achieve maximal signaling.
Is hypercapnia associated with poor prognosis in chronic obstructive pulmonary disease? A long-term follow-up cohort study
Authors: Yang Hui , Xiang Pingchao , Zhang Erming , Guo Weian , Shi Yanwei , Zhang Shuo , Tong Zhaohui 
Published: December 2015

ObjectivesTo assess whether hypercapnia may predict the prognosis in chronic obstructive pulmonary disease (COPD).DesignProspective cohort study comparing the survival of patients with COPD and normocapnia to those with chronic hypercapnia.SettingPatients with consecutive COPD were enrolled between 1 May 1993 and 31 October 2006 at two medical centres. Follow-up was censored on 31 October 2011.ParticipantsA total of 275 patients with stable COPD and aged 40–85 years were enrolled. Diagnosis of hypercapnia was confirmed by blood gas analysis. Patients with near-terminal illness or comorbidities that affect PaCO2(obstructive sleep apnoea, obesity-related hypoventilation, or neuromuscular disease) were excluded. The outcome of 98 patients with normocapnia and 177 with chronic hypercapnia was analysed.Outcome measuresOverall survival.ResultsMedian survival was longer in patients with normocapnia than in those with hypercapnia (6.5 vs 5.0 years, p=0.016). Multivariate COX regression analysis indicated that age (HR=1.043, 95% CI 1.012 to 1.076), Charlson Index, which is a measure of comorbidity (HR=1.172, 95% CI 1.067 to 1.288), use of medication (HR=0.565, 95% CI 0.379 to 0.842), body mass index (BMI) (HR=0.922, 95% CI 0.883 to 0.963), PaCO2(HR=1.026, 95% CI 1.011 to 1.042), Cor pulmonale (HR=2.164, 95% CI 1.557 to 3.006), non-invasive positive-pressure ventilation (NPPV) (HR=0.615, 95% CI 0.429 to 0.881) and per cent of forced expiratory volume in 1 s (FEV1%) (HR=0.979, 95% CI 0.967 to 0.991), were independent risk factors for mortality.ConclusionsIncreased age, Charlson Index, chronic hypercapnia and Cor pulmonale, and decreased FEV1%, use of medication, BMI and NPPV, were associated with a poor prognosis in patients with COPD.
It's Totally Tubular…Riding The New Wave of Ovarian Cancer Research
Authors: Perets Ruth , Drapkin Ronny 
Published: December 2015

Abstract
Hereditary breast and ovarian cancer syndrome carries significant mortality for young women if effective preventive and screening measures are not taken. Preventive salpingo-oophorectomy is currently the only method known to reduce the risk of ovarian cancer-related death. Histopathological analyses of these surgical specimens indicate that a high proportion of ovarian cancers in women at high risk and in the general population arise from the fallopian tube. This paradigm shift concerning the cell of origin for the most common subtype of ovarian cancer, high-grade serous carcinoma, has sparked a major effort within the research community to develop new and robust model systems to study the fallopian tube epithelium as the cell of origin of “ovarian” cancer. In this review, evidence supporting the fallopian tube as the origin of ovarian cancer is presented as are novel experimental model systems for studying the fallopian tube epithelium in high-risk women as well as in the general population. This review also addresses the clinical implications of the newly proposed cell of origin, the clinical questions that arise, and novel strategies for ovarian cancer prevention. Cancer Res; 76(1); 10–17. ©2015 AACR.
Assessing the Cumulative Contribution of New and Established Common Genetic Risk Factors to Early-Onset Prostate Cancer
Authors: Lange Ethan M. , Ribado Jessica V. , Zuhlke Kimberly A. , Johnson Anna M. , Keele Gregory R. , Li Jin , Wang Yunfei , Duan Qing , Li Ge , Gao Zhengrong , Li Yun , Xu Jianfeng , Zheng S. Lilly , Cooney Kathleen A. 
Published: December 2015

Abstract
Background: We assessed the evidence for association between 23 recently reported prostate cancer variants and early-onset prostate cancer and the aggregate value of 63 prostate cancer variants for predicting early-onset disease using 931 unrelated men diagnosed with prostate cancer prior to age 56 years and 1,126 male controls.
Methods: Logistic regression models were used to test the evidence for association between the 23 new variants and early-onset prostate cancer. Weighted and unweighted sums of total risk alleles across these 23 variants and 40 established variants were constructed. Weights were based on previously reported effect size estimates. Receiver operating characteristic curves and forest plots, using defined cut-points, were constructed to assess the predictive value of the burden of risk alleles on early-onset disease.
Results: Ten of the 23 new variants demonstrated evidence (P &lt; 0.05) for association with early-onset prostate cancer, including four that were significant after multiple test correction. The aggregate burden of risk alleles across the 63 variants was predictive of early-onset prostate cancer (AUC = 0.71 using weighted sums), especially in men with a high burden of total risk alleles.
Conclusions: A high burden of risk alleles is strongly associated with early-onset prostate cancer.
Impact: Our results provide the first formal replication for several of these 23 new variants and demonstrate that a high burden of common-variant risk alleles is a major risk factor for early-onset prostate cancer. Cancer Epidemiol Biomarkers Prev; 25(5); 766–72. ©2015 AACR.
Sustained Production of Multidecadal Climate Records: Lessons from the NOAA Climate Data Record Program
Authors: Bates John J. , Privette Jeffrey L. , Kearns Edward J. , Glance Walter , Zhao Xuepeng 
Published: December 2015

Abstract
The key objective of the NOAA Climate Data Record (CDR) program is the sustained production of high-quality, multidecadal time series data describing the global atmosphere, oceans, and land surface that can be used for informed decision-making. The challenges of a long-term program of sustaining CDRs, as contrasted with short-term efforts of traditional 3-yr research programs, are substantial. The sustained production of CDRs requires collaboration between experts in the climate community, data management, and software development and maintenance. It is also informed by scientific application and associated user feedback on the accessibility and usability of the produced CDRs. The CDR program has developed a metric for assessing the maturity of CDRs with respect to data management, software, and user application and applied it to over 30 CDRs. The main lesson learned over the past 7 years is that a rigorous team approach to data management, employing subject matter experts at every step, is critical to open and transparent production. This approach also makes it much easier to support the needs of users who want near-real-time production of CDRs for monitoring and users who want to use CDRs for tailored, derived information, such as a drought index.
Comparison of Integrated Multisatellite Retrievals for GPM (IMERG) and TRMM Multisatellite Precipitation Analysis (TMPA) Monthly Precipitation Products: Initial Results
Authors: Liu Zhong 
Published: December 2015

Abstract
Launched on 27 February 2014, the Global Precipitation Measurement (GPM) mission comprises an international constellation of satellites to provide the next generation of global observations of precipitation. Built upon the success of the widely used TRMM Multisatellite Precipitation Analysis (TMPA) products, the Integrated Multisatellite Retrievals for GPM (IMERG) products continue to make improvements in areas such as spatial and temporal resolutions and snowfall estimates, etc., which will be valuable for research and applications. During the transition from TMPA to IMERG, characterizing the differences between these two product suites is important in order for users to make adjustments in research and applications accordingly. In this study, the newly released IMERG Final Run monthly product is compared with the TMPA monthly product (3B43) in the boreal summer of 2014 and the boreal winter of 2014/15 on a global scale. The results show the IMERG monthly product can capture major heavy precipitation regions in the Northern and Southern Hemispheres reasonably well. Differences between IMERG and 3B43 vary with surface types and precipitation rates in both seasons. Over land, systematic differences are much smaller compared to those over ocean because of the similar gauge adjustment used in the two monthly products. Positive relative differences (IMERG &gt; 3B43) are primarily found at low precipitation rates and negative differences (IMERG &lt; 3B43) at high precipitation rates. Over ocean, negative systematic differences (IMERG &lt; 3B43) prevail at all precipitation rates. Analysis of the passive microwave (PMW) and infrared (IR) monthly products from TMPA and IMERG shows the large systematic differences in the tropical oceans are closely associated with the differences in the PMW products.
von Willebrand factor is dimerized by protein disulfide isomerase
Authors: Lippok Svenja , Kolšek Katra , Löf Achim , Eggert Dennis , Vanderlinden Willem , Müller Jochen P. , König Gesa , Obser Tobias , Röhrs Karoline , Schneppenheim Sonja , Budde Ulrich , Baldauf Carsten , Aponte-Santamaría Camilo , Gräter Frauke , Schneppenheim Reinhard , Rädler Joachim O. , Brehm Maria A. 
Published: December 2015

Key Points
The protein disulfide isomerase is involved in VWF dimerization by initiating disulfide bond formation at cysteines 2771 and 2773. von Willebrand disease-associated mutations in the dimerization domain of von Willebrand factor disturb processing by the protein disulfide isomerase.
Multiple and Secondary Hormone Secretion in Patients With Metastatic Pancreatic Neuroendocrine Tumours
Authors: Crona Joakim , Norlén Olov , Antonodimitrakis Pantelis , Welin Staffan , Stålberg Peter , Eriksson Barbro 
Published: December 2015

Abstract

Context:
As a group, neuroendocrine tumors (NETs) secrete many different peptide hormones, yet heretofore each NET patient is typically thought to produce at most one hormone that causes a distinct hormonal syndrome. A minority of patients have multiple hormones at diagnosis and may also develop secondary hormone secretion at a later stage.

Objectives:
The objectives of the study were to determine the frequency and to describe the impact of multiple and secondary hormone secretion in sporadic gasteroenteropancreatic NET patients.

Design, Setting, and Participants:
This was a retrospective analysis of patients (n = 972) with gasteroenteropancreatic NET treated at Uppsala University Hospital, Uppsala, Sweden. Patients with the secretion of multiple hormones at diagnosis and/or those developing secondary hormone secretion during the disease course were identified and studied in further detail.

Results:
In pancreatic NETs (PNETs), a total of 19 of 323 patients (6%) had secretion of multiple hormones at diagnosis, and 14 of 323 (4%) had secondary changes during the disease course. These phenomena occurred exclusively in patients with an advanced disease stage, and secondary hormones were detected in a close time span with progressive disease. Patients with secondary insulin hypersecretion had increased morbidity as well as reduced survival (P &lt; .002). In contrast, multiple and secondary hormone secretion was rarely seen in NETs of the small intestine with 0 and 1 of 603 cases, respectively.

Conclusion:
Diversity of PNET hormone secretion either at diagnosis or during the disease course occurred in a minority of patients (9.3%). These phenomena had a major impact on patient outcome both through increased morbidity and mortality. Our results support that patients with metastatic PNETs should be monitored for clinical symptoms of secondary hormone secretion during the disease course.
Infection with schistosome parasites in snails leads to increased predation by prawns: implications for human schistosomiasis control
Authors: Swartz Scott J. , De Leo Giulio A. , Wood Chelsea L. , Sokolow Susanne H. 
Published: December 2015

ABSTRACT
Schistosomiasis – a parasitic disease that affects over 200 million people across the globe – is primarily transmitted between human definitive hosts and snail intermediate hosts. To reduce schistosomiasis transmission, some have advocated disrupting the schistosome life cycle through biological control of snails, achieved by boosting the abundance of snails' natural predators. But little is known about the effect of parasitic infection on predator–prey interactions, especially in the case of schistosomiasis. Here, we present the results of laboratory experiments performed on Bulinus truncatus and Biomphalaria glabrata snails to investigate: (i) rates of predation on schistosome-infected versus uninfected snails by a sympatric native river prawn, Macrobrachium vollenhovenii, and (ii) differences in snail behavior (including movement, refuge-seeking and anti-predator behavior) between infected and uninfected snails. In predation trials, prawns showed a preference for consuming snails infected with schistosome larvae. In behavioral trials, infected snails moved less quickly and less often than uninfected snails, and were less likely to avoid predation by exiting the water or hiding under substrate. Although the mechanism by which the parasite alters snail behavior remains unknown, these results provide insight into the effects of parasitic infection on predator–prey dynamics and suggest that boosting natural rates of predation on snails may be a useful strategy for reducing transmission in schistosomiasis hotspots.
Special Features of Reactor Coolant Pipe Inspection Exampled by Testing of Weld Specimen
Authors: Титов  , Titov Vyacheslav 
Published: December 2015

Introduction. Testing of reactor coolant pipe (RCP) weld joints and matters of testing quality ensuring are considered in the article. The aim of the study was to demonstrate the potential of phased array ultrasonic systems for testing of RCP as well as to show capabilities of portable X-ray fluorescence analyzers for composition express analysis of weld joints.
Method. Real fragments of RCP weld joints Du580 were chosen for the experiment. Phased array ultrasonic flaw detector OmniScan MX was used as a testing instrument; testing data were analyzed and interpreted with TomoView software. Chemical analysis was fulfilled with PMI Master UVR and Olympus DELTA devices.
Results. Fragments of RCP weld joints Du580 have been examined. Chemical analysis results have confirmed that a portable X-ray fluorescence analyzer can be used for determining the main alloying elements. Benefits and drawbacks of phased array ultrasonic testing for RCP weld joints have been revealed; recommendations for time corrected gain adjustment and pulse repetition frequency selection have been given; questions of improvement of testing productivity and quality have been considered.
Conclusion. Application of phased array at ultrasonic testing of complex and important objects increases objectivity of the testing results. Using real fragments of reactor coolant pipe as specimens for adjustment makes it possible both to avoid interpretation mistakes and develop detailed testing techniques.
Ultrasonic Testing of Railway Transport Units with Phased Array Flaw Detectors. Part 2
Authors: Сойфер  , Soyfer Yuriy , Макарова  , Makarova Taisiya , Мелешко  , Meleshko Nataliya , Жаринов  , Zharinov Sergey 
Published: December 2015

The second part of the article describes possibilities of phased array flaw detectors application for testing of railway transport units, such as solebars of freight cars. The task was to reproduce the standard testing procedures using phased array flaw detectors and demonstrate their advantages in visibility, efficiency, repeatability, results validity. Unfortunately, one of the main advantages of phased array flaw detectors, namely – a possibility to control the focusing depth – is lost while testing of large scale objects.
Sector scanning technique with the phased array flaw detectors OmniScan and Isonic 2010 in the minimum configuration was used for the research. In the all cases acoustical images of the side drilled holes and natural defects in solebars were obtained within the range of selected angles.
Solebar testing has been more complicated because of a form and irregularity of scanning surface, necessity of its cleaning and a complex profile of back surface. Nevertheless the usage of phased array flaw detectors has made it possible to identify the back surface profile.
Application of phased arrays substantially increases testing efficiency and improves visibility of obtained results.
Method activation end date in the past. direction:re
Authors: Булыга  , Bulyga R. 
Published: December 2015

Th e article contains a review of modern concepts of how to compile an organization’s complex public reports. It
focuses on the leading Russian scientifi c school in this area. Th e author provides the review of the recent publications of
the scientists belonging to this school; presents the scheme of such category as business as a triad of capital, transaction
and performance results; off ers a schematic structure of the notion “intellectual capital of business”.