bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Essential Poison: Synthesis and Degradation of Cyclic Di-AMP in Bacillus subtilis
Authors: Gundlach Jan , Mehne Felix M. P. , Herzberg Christina , Kampf Jan , Valerius Oliver , Kaever Volkhard , Stülke Jörg 
Published: August 2015

ABSTRACTGram-positive bacteria synthesize the second messenger cyclic di-AMP (c-di-AMP) to control cell wall and potassium homeostasis and to secure the integrity of their DNA. In the firmicutes, c-di-AMP is essential for growth. The model organismBacillus subtilisencodes three diadenylate cyclases and two potential phosphodiesterases to produce and degrade c-di-AMP, respectively. Among the three cyclases, CdaA is conserved in nearly all firmicutes, and this enzyme seems to be responsible for the c-di-AMP that is required for cell wall homeostasis. Here, we demonstrate that CdaA localizes to the membrane and forms a complex with the regulatory protein CdaR and the glucosamine-6-phosphate mutase GlmM. Interestingly,cdaA,cdaR, andglmMform a gene cluster that is conserved throughout the firmicutes. This conserved arrangement and the observed interaction between the three proteins suggest a functional relationship. Our data suggest that GlmM and GlmS are involved in the control of c-di-AMP synthesis. These enzymes convert glutamine and fructose-6-phosphate to glutamate and glucosamine-1-phosphate. c-di-AMP synthesis is enhanced if the cells are grown in the presence of glutamate compared to that in glutamine-grown cells. Thus, the quality of the nitrogen source is an important signal for c-di-AMP production. In the analysis of c-di-AMP-degrading phosphodiesterases, we observed that both phosphodiesterases, GdpP and PgpH (previously known as YqfF), contribute to the degradation of the second messenger. Accumulation of c-di-AMP in agdpP pgpHdouble mutant is toxic for the cells, and the cells respond to this accumulation by inactivation of the diadenylate cyclase CdaA.IMPORTANCEBacteria use second messengers for signal transduction. Cyclic di-AMP (c-di-AMP) is the only second messenger known so far that is essential for a large group of bacteria. We have studied the regulation of c-di-AMP synthesis and the role of the phosphodiesterases that degrade this second messenger. c-di-AMP synthesis strongly depends on the nitrogen source: glutamate-grown cells produce more c-di-AMP than glutamine-grown cells. The accumulation of c-di-AMP in a strain lacking both phosphodiesterases is toxic and results in inactivation of the diadenylate cyclase CdaA. Our results suggest that CdaA is the critical diadenylate cyclase that produces the c-di-AMP that is both essential and toxic upon accumulation.
Is young fatherhood causally related to midlife mortality? A sibling fixed-effect study in Finland
Authors: Einiö Elina , Nisén Jessica , Martikainen Pekka 
Published: August 2015

BackgroundPrevious studies have shown that young fatherhood is associated with higher later-life mortality. It is unclear whether the association is credible, in the sense that mortality and young fatherhood appear to be associated because both are determined by family-related environmental, socioeconomic and genetic characteristics.MethodsWe used a household-based 10% sample drawn from the 1950 Finnish census to estimate all-cause mortality of fathers born during 1940–1950. The fathers were followed from age 45 until death, or the end of age 54. We used a standard Cox model and a sibling fixed-effects Cox model to examine whether the effect of young fatherhood was independent of observed adulthood characteristics and unobserved early-life characteristics shared by brothers.ResultsMen who had their first child before the age of 22 or at ages 22–24 had higher mortality as compared with their brothers who had their first child at the median or mean age of 25–26. Men who had their first child later at ages 30–44 had lower mortality than their brothers who had a first child before the age of 25. The pattern of results from a standard model was similar to that obtained from a fixed-effects sibling model.ConclusionsThe findings suggest a causal effect of young fatherhood on mortality and highlight the need to support young fathers in their family life to improve health behaviours and health.
New magnetostratigraphic dating of the Palaeogene syntectonic sediments of the west-central Pyrenees: tectonostratigraphic implications
Authors: Oliva-Urcia Belén , Beamud Elisabet , Garcés Miguel , Arenas Concha , Soto Ruth , Pueyo Emilio L. , Pardo Gonzalo 
Published: August 2015

Abstract

New magnetostratigraphic results from a 3300 m-thick section across the syntectonic fluvial sediments of the Campodarbe Formation (Upper Eocene–Oligocene) in the Ebro foreland basin (NE Spain) are presented. The new data allow the top of the Campodarbe Formation to be correlated to Chron 7r (Chattian), younger than previously stated (C10r), therefore shifting the age of significant palaeogeographical changes in the foreland basin. The deformation in the southern front produces the cannibalization in the piggyback basin of 1300 m of sediments spanning
c.
3.7 Myr. Average accumulation rates are lower in the Ebro foreland basin than in the piggyback basin and decrease from 35 to 27 cm kyr
−1
by the time the San Felices thrust sheet activity decelerates (at
c.
28 Myr). Shifts of accumulation rates result from accommodation space changes, which occur locally and are linked to the activity of the San Felices thrust, while the sediment supply occurs at orogenic scale (source of sediments is
c.
200 km to the NE). Finally, sequence boundaries previously considered isochronous in the continental record of the Cenozoic Pyrenean basins are revealed to be 1.8–1 Myr older in the piggyback basin than in the Ebro foreland basin.
Size of the Optic Nerve Head and Its Relationship with the Thickness of the Macular Ganglion Cell Complex and Peripapillary Retinal Nerve Fiber Layer in Patients with Primary Open Angle Glaucoma
Authors: Enomoto Nobuko , Anraku Ayako , Ishida Kyoko , Takeyama Asuka , Yagi Fumihiko , Tomita Goji 
Published: August 2015

Purpose. To evaluate the relationships among the optic nerve head (ONH) area, macular ganglion cell complex (mGCC) thickness, circumpapillary retinal nerve fiber layer (cpRNFL) thickness, and visual field defects in patients with primary open angle glaucoma (POAG).Methods. This retrospective study included 90 eyes of 90 patients with POAG. The ONH area, rim area, mGCC thickness, and cpRNFL thickness were measured using optical coherence tomography. Mean deviation (MD) was measured using standard automated perimetry. The relationships among clinical factors including age, refraction, the ONH area, the rim area, the mGCC thickness, the cpRNFL thickness, and MD were evaluated using correlation coefficients and multiple regression analyses.Results. The significant correlation of the ONH area with refraction (r=0.362,P<0.001), the mGCC thickness (r=0.225,P=0.033), and the cpRNFL thickness (r=0.253,P=0.016) was found. Multiple regression analysis showed that the ONH area, rim area, and MD were selected as significant contributing factors to explain the mGCC thickness and cpRNFL thickness. No factor was selected to explain MD.Conclusions. The ONH area, in other words, the disc size itself may affect the mGCC thickness and cpRNFL thickness in POAG patients.Erratum to “Size of the Optic Nerve Head and Its Relationship with the Thickness of the Macular Ganglion Cell Complex and Peripapillary Retinal Nerve Fiber Layer in Patients with Primary Open Angle Glaucoma”
VR23: A Quinoline–Sulfonyl Hybrid Proteasome Inhibitor That Selectively Kills Cancer via Cyclin E–Mediated Centrosome Amplification
Authors: Pundir Sheetal , Vu Hai-Yen , Solomon V. Raja , McClure Rebecca , Lee Hoyun 
Published: August 2015

Abstract
The proteasome is clinically validated as a target for cancer therapeutics. However, proteasome-inhibitory agents that are cancer selective have yet to be developed. In this study, we report the identification of a safe and effective proteasome inhibitor with selective anticancer properties. We screened a chemical library constructed using a hybrid approach that incorporated a 4-piperazinylquinoline scaffold and a sulfonyl phamarcophore. From this library, we identified 7-chloro-4-(4-(2,4-dinitrophenylsulfonyl)piperazin-1-yl)quinoline (VR23) as a small molecule that potently inhibited the activities of trypsin-like proteasomes (IC50 = 1 nmol/L), chymotrypsin-like proteasomes (IC50 = 50–100 nmol/L), and caspase-like proteasomes (IC50 = 3 μmol/L). Data from molecular docking and substrate competition assays established that the primary molecular target of VR23 was β2 of the 20S proteasome catalytic subunit. Notably, VR23 was structurally distinct from other known proteasome inhibitors and selectively killed cancer cells by apoptosis, with little effect on noncancerous cells. Mechanistic investigations showed that cancer cells exposed to VR23 underwent an abnormal centrosome amplification cycle caused by the accumulation of ubiquitinated cyclin E. In combinations with the clinically approved chymotrypsin-like proteasome inhibitor bortezomib, VR23 produced a synergistic effect in killing multiple myeloma cells, including those that were resistant to bortezomib. VR23 was effective in vivo in controlling multiple myelomas and metastatic breast cancer cells, in the latter case also enhancing the antitumor activity of paclitaxel while reducing its side effects. Overall, our results identify VR23 as a structurally novel proteasome inhibitor with desirable properties as an anticancer agent. Cancer Res; 75(19); 4164–75. ©2015 AACR.
Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Adenocarcinoma
Authors: Radon Tomasz P. , Massat Nathalie J. , Jones Richard , Alrawashdeh Wasfi , Dumartin Laurent , Ennis Darren , Duffy Stephen W. , Kocher Hemant M. , Pereira Stephen P. , Guarner (posthumous) Luisa , Murta-Nascimento Cristiane , Real Francisco X. , Malats Núria , Neoptolemos John , Costello Eithne , Greenhalf William , Lemoine Nick R. , Crnogorac-Jurcevic Tatjana 
Published: August 2015

Abstract
Purpose: Noninvasive biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) are currently not available. Here, we aimed to identify a set of urine proteins able to distinguish patients with early-stage PDAC from healthy individuals.
Experimental design: Proteomes of 18 urine samples from healthy controls, chronic pancreatitis, and patients with PDAC (six/group) were assayed using GeLC/MS/MS analysis. The selected biomarkers were subsequently validated with ELISA assays using multiple logistic regression applied to a training dataset in a multicenter cohort comprising 488 urine samples.
Results: LYVE-1, REG1A, and TFF1 were selected as candidate biomarkers. When comparing PDAC (n = 192) with healthy (n = 87) urine specimens, the resulting areas under the receiver-operating characteristic curves (AUC) of the panel were 0.89 [95% confidence interval (CI), 0.84–0.94] in the training (70% of the data) and 0.92 (95% CI, 0.86–0.98) in the validation (30% of the data) datasets. When comparing PDAC stage I–II (n = 71) with healthy urine specimens, the panel achieved AUCs of 0.90 (95% CI, 0.84–0.96) and 0.93 (95% CI, 0.84–1.00) in the training and validation datasets, respectively. In PDAC stage I–II and healthy samples with matching plasma CA19.9, the panel achieved a higher AUC of 0.97 (95% CI, 0.94–0.99) than CA19.9 (AUC = 0.88; 95% CI, 0.81–0.95, P = 0.005). Adding plasma CA19.9 to the panel increased the AUC from 0.97 (95% CI, 0.94–0.99) to 0.99 (95% CI, 0.97–1.00, P = 0.04), but did not improve the comparison of stage I–IIA PDAC (n = 17) with healthy urine.
Conclusions: We have established a novel, three-protein biomarker panel that is able to detect patients with early-stage pancreatic cancer in urine specimens. Clin Cancer Res; 21(15); 3512–21. ©2015 AACR.
Wpływ języka rosyjskiego na zasób leksykalny polskiej gwary mieszkańców Wierszyny na Syberii
Authors: Paśko-Koneczniak Dorota 
Published: August 2015

The influence of the Russian language on the vocabulary in the Polish dialect of the inhabitants of Vershina in SiberiaVershina is a Polish village in Siberia. It is situated 130 kilometres north of Irkutsk. The village was founded by the Polish settlers in 1910, and it was part of the planned voluntary colonisation of Siberia. The colonisers came from the territory that had formerly been annexed to Russia, namely Zagłębie and Małopolska. The inhabitants of Vershina are a bilingual community: they use the Polish dialect and the Russian language interchangeably, depending on the communicative context. The dialect in question is a unique insular dialect, as many inhabitants of Vershina are in contact with the Polish educated language, thanks to their visits to Poland. Some have even graduated from Polish universities. The interaction between the Polish dialect and the Russian language leads to the process of linguistic interference, which is noticeable especially in the sphere of vocabulary. The lexicon is the fastest-changing element of the language. With the appearance of new aspects of reality, there come into being new designations. The influence of the Russian language on the Polish dialect is equated with a variety of distinct phenomena. In the dialect studied there are a lot of borrowings, calques and hybrids. The words borrowed include mainly the vocabulary connected with health, jobs and professions, technical advancement, as well as the Siberian and Soviet reality. Влияние русского языка на лексику польского говора жителей деревни Вершина в СибириВершина – польское село в Сибири, расположенное в 130 км к северу от Иркутска. Деревня была основана польскими переселенцами в 1910 году в рамках добровольного и планированного заселения Сибири. Колонизаторами были крестьяне из Королества Польского, входившего в состав Российской империи – из Силезского угольного бассейна и Малой Польши. Жители Вершины являются билингвами и употребляют польский говор и русский язык попеременно, в зависимости от коммуникативной ситуации. Говор Вершины представляет собой особенный тип говора, так как многие жители этой деревни имеют контакт с польским литературным языком благодаря поездкам в Польшу и учёбе. (Некоторые даже получили в Польше высшее образование). При контакте польского говора с русским языком наблюдается интерференция, прежде всего в лексике. Лексика подвергается самым бы стрым изменениям. Недостающие в польском речевом обиходе слова жители Вершины компенсируют русскими. Это влияние представлено разнообразными языковыми явлениями (заимствованиями, калькированием, образованием, гибридов и т. п.). Заимствования чаще всего касаются сферы сибирской и советской действительности, техники, а также названий, связанных со здоровьем, и названий профессий.
Analiza semantyczna przewisk staroobrzędowców z okolic Augustowa i Suwałk
Authors: Ziółkowska Magdalena 
Published: August 2015

The semantic analysis of nicknames of Old Believers’ from Augustów and Suwalki regionsThe Old Believers settled down in North-Eastern Poland in the second half of the 18th century. They were living in hermetic, homogenous communities. This protected their culture from strong exterior influence. Nowadays, after a number of civilizing transformations, the isolation practically disappeared making the Old Believers’ culture defenceless against influence of dominant Polish culture. Together with all that changes the Old Believers’ anthroponymy has been transformed. Nicknames used to be were very popular in Old Believers’ community. Giving nicknames is still a living only in villages Gabowe Grądy and Bór. The most numerous group are nicknames motivated by appellatives that define external inner features, temperament and habits. These names reflect the objective knowledge of the nickname makers and they are expressed by concrete vocabulary. Семантический анализ прозвищ у старообрядцев из окрестностей городов Августов и СувалкиСтароверы появились на территории современной Польши в конце XVIII столетия. Они прибыли сюда из окрестностей Великие Луки и принесли с собой часть культурного наследия той территории, также язык и антропонимическую систему. Прозвища староверов представляют собой интерес с точки зрения их происхождения. Некоторые из них образованы от диалектных слов. Многие имеют свои эквиваленты как в русском, так и в польском языках, что является доказательством параллельного функционирования в их группе двух языков и двух культур в их обществе. До второй мировой войны прозвища были распространены среди старообрядцев, проживающих в разных местах их проживания в Польше. В настоящее время они популярны лишь в деревнях Габове Гронды и Бур, поскольку только здесь старообрядцы проживают в компактной среде. В речи старообрядцев встречаем несколько видов прозвищ: прозвища, образованные от аппелятивов, прозвища – цитаты, прозвища, образованные от имён собственных.
How Has Subtropical Stratocumulus and Associated Meteorology Changed since the 1980s?*
Authors: Seethala C. , Norris Joel R. , Myers Timothy A. 
Published: August 2015

Abstract
The importance of low-level cloud feedbacks to climate sensitivity motivates an investigation of how low-level cloud amount and related meteorological conditions have changed in recent decades in subtropical stratocumulus regions. Using satellite cloud datasets corrected for inhomogeneities, it is found that during 1984–2009 low-level cloud amount substantially increased over the northeastern Pacific, southeastern Pacific, and southeastern Atlantic; decreased over the northeastern Atlantic; and weakly increased over the southeastern Indian Ocean subtropical stratocumulus regions. Examination of meteorological parameters from four reanalyses indicates that positive trends in low-level cloud amount are associated with cooler sea surface temperature, greater inversion strength, and enhanced cold-air advection. The converse holds for negative trends in low-level cloud amount. A multilinear regression model based on these three meteorological variables reproduces the sign and magnitude of observed cloud amount trends in all stratocumulus regions within the range of observational uncertainty. Changes in inversion strength have the largest independent effect on cloud trends, followed by changes in advection strength. Changes in sea surface temperature have the smallest independent effect on cloud trends. Differing signs of cloud trends and differing contributions from meteorological parameters suggest that observed changes in subtropical stratocumulus since the 1980s may be due to natural variability rather than a systematic response to climate change.
A Hydrometeor Classification Method for X-Band Polarimetric Radar: Construction and Validation Focusing on Solid Hydrometeors under Moist Environments
Authors: Kouketsu Takeharu , Uyeda Hiroshi , Ohigashi Tadayasu , Oue Mariko , Takeuchi Hiroto , Shinoda Taro , Tsuboki Kazuhisa , Kubo Mamoru , Muramoto Ken-ichiro 
Published: August 2015

AbstractA fuzzy-logic-based hydrometeor classification (HC) method for X-band polarimetric radar (X-pol), which is suitable for observation of solid hydrometeors under moist environments producing little or no hail, is constructed and validated. This HC method identifies the most likely hydrometeor at each radar sampling volume from eight categories: 1) drizzle, 2) rain, 3) wet snow aggregates, 4) dry snow aggregates, 5) ice crystals, 6) dry graupel, 7) wet graupel, and 8) rain–hail mixture. Membership functions are defined on the basis of previous studies. The HC method uses radar reflectivity Zh, differential reflectivity Zdr, specific differential phase Kdp, and correlation coefficient ρhv as its main inputs, and temperature with some consideration of relative humidity as supplemental information. The method is validated against ground and in situ observations of solid hydrometeors (dry graupel, dry snow aggregates, and ice crystals) under a moist environment. Observational data from a ground-based imaging system are used to validate the HC method for dry graupel and dry snow aggregates. For dry snow aggregates and ice crystals, the HC method is validated using simultaneous observations from a balloonborne instrument [hydrometeor videosonde (HYVIS)] and an X-pol range–height indicator directed toward the HYVIS. The HC method distinguishes effectively between dry graupel, dry snow aggregates, and ice crystals, and is therefore valid for HC under moist environments.
Extending the Square Root Method to Account for Additive Forecast Noise in Ensemble Methods
Authors: Raanes Patrick Nima , Carrassi Alberto , Bertino Laurent 
Published: August 2015

Abstract
A square root approach is considered for the problem of accounting for model noise in the forecast step of the ensemble Kalman filter (EnKF) and related algorithms. The primary aim is to replace the method of simulated, pseudo-random additive so as to eliminate the associated sampling errors. The core method is based on the analysis step of ensemble square root filters, and consists in the deterministic computation of a transform matrix. The theoretical advantages regarding dynamical consistency are surveyed, applying equally well to the square root method in the analysis step. A fundamental problem due to the limited size of the ensemble subspace is discussed, and novel solutions that complement the core method are suggested and studied. Benchmarks from twin experiments with simple, low-order dynamics indicate improved performance over standard approaches such as additive, simulated noise, and multiplicative inflation.
Evaluation of a Probabilistic Forecasting Methodology for Severe Convective Weather in the 2014 Hazardous Weather Testbed
Authors: Karstens Christopher D. , Stumpf Greg , Ling Chen , Hua Lesheng , Kingfield Darrel , Smith Travis M. , Correia James , Calhoun Kristin , Ortega Kiel , Melick Chris , Rothfusz Lans P. 
Published: August 2015

AbstractA proposed new method for hazard identification and prediction was evaluated with forecasters in the National Oceanic and Atmospheric Administration Hazardous Weather Testbed during 2014. This method combines hazard-following objects with forecaster-issued trends of exceedance probabilities to produce probabilistic hazard information, as opposed to the static, deterministic polygon and attendant text product methodology presently employed by the National Weather Service to issue severe thunderstorm and tornado warnings. Three components of the test bed activities are discussed: usage of the new tools, verification of storm-based warnings and probabilistic forecasts from a control–test experiment, and subjective feedback on the proposed paradigm change. Forecasters were able to quickly adapt to the new tools and concepts and ultimately produced probabilistic hazard information in a timely manner. The probabilistic forecasts from two severe hail events tested in a control–test experiment were more skillful than storm-based warnings and were found to have reliability in the low-probability spectrum. False alarm area decreased while the traditional verification metrics degraded with increasing probability thresholds. The latter finding is attributable to a limitation in applying the current verification methodology to probabilistic forecasts. Relaxation of on-the-fence decisions exposed a need to provide information for hazard areas below the decision-point thresholds of current warnings. Automated guidance information was helpful in combating potential workload issues, and forecasters raised a need for improved guidance and training to inform consistent and reliable forecasts.