bluuebunny/crossref_metadata_2025 huggingface dataset:
Flubromazolam – Basic pharmacokinetic evaluation of a highly potent designer benzodiazepine
Authors: Huppertz Laura M. , Moosmann Bjoern , Auwärter Volker
Published: April 2017

Since their first appearance on the Internet in 2012, designer benzodiazepines established as an additional, quickly growing compound class among new psychoactive substances. Data regarding pharmacokinetic parameters, metabolism, and detectability for new compounds are limited or often not available. One of these compounds, flubromazolam (8‐bromo‐6‐(2‐fluorophenyl)‐1‐methyl‐4H‐[1,2,4]triazolo[4,3‐a][1,4]benzodiazepine), the triazolo‐analogue of flubromazepam, has been offered on the Internet from 2014 on. The purpose of the present study was to assess the period of detectability in biological samples along with preliminary basic pharmacokinetic parameters of the designer benzodiazepine flubromazolam. To investigate these, one of the authors ingested a capsule containing 0.5 mg of the drug. Metabolism studies and suitability tests for the detection with immunochemical assays were performed with the samples obtained from the self‐experiment and five authentic case samples. Flubromazolam and its mono‐hydroxylated metabolite were detectable by liquid chromatography–tandem mass spectrometry (LC–MS/MS) in urine for up to 6.5 and 8 days, respectively (lower limit of quantification (LLOQ) flubromazolam: 0.1 ng/mL). Peak serum concentrations were as low as 8 ng/mL (8 h post ingestion). Glucuronides were also detected. The terminal elimination half‐life could be estimated in the range of 10–20 h. Immunochemical assays yielded negative results for serum samples and positive results for urine samples for up to five days post ingestion. The presented data demonstrate the detectability of a single uptake of 0.5 mg of flubromazolam in hair samples collected two weeks after drug uptake by LC–MS3(cmax0.6 pg/mg; LOD 0.01 pg/mg). The detected metabolites were in good agreement with those described in other studies. Copyright © 2017 John Wiley & Sons, Ltd.
Brain morphology of the threespine stickleback (Gasterosteus aculeatus) varies inconsistently with respect to habitat complexity: A test of the Clever Foraging Hypothesis
Authors: Ahmed Newaz I. , Thompson Cole , Bolnick Daniel I. , Stuart Yoel E.
Published: April 2017

The Clever Foraging Hypothesis asserts that organisms living in a more spatially complex environment will have a greater neurological capacity for cognitive processes related to spatial memory, navigation, and foraging. Because the telencephalon is often associated with spatial memory and navigation tasks, this hypothesis predicts a positive association between telencephalon size and environmental complexity. The association between habitat complexity and brain size has been supported by comparative studies across multiple species but has not been widely studied at the within‐species level. We tested for covariation between environmental complexity and neuroanatomy of threespine stickleback (Gasterosteus aculeatus) collected from 15 pairs of lakes and their parapatric streams on Vancouver Island. In most pairs, neuroanatomy differed between the adjoining lake and stream populations. However, the magnitude and direction of this difference were inconsistent between watersheds and did not covary strongly with measures of within‐site environmental heterogeneity. Overall, we find weak support for the Clever Foraging Hypothesis in our study.
Seasonal abundance and habitat use of bird species in and around Wondo Genet Forest, south‐central Ethiopia
Authors: Girma Zerihun , Mamo Yosef , Mengesha Girma , Verma Ashok , Asfaw Tsyon
Published: April 2017

The habitat use and seasonal migratory pattern of birds in Ethiopia is less explored as compared to diversity studies. To this end, this study aimed at investigating the patterns of distribution related to seasonality and the effect of habitat characteristics (elevation, slope, and average vegetation height) on habitat use of birds of Wondo Genet Forest Patch. A stratified random sampling design was used to assess the avian fauna across the four dominant habitat types found in the study area: natural forest, wooded grassland, grassland, and agroforestry land. A point transect count was employed to investigate avian species richness and abundance per habitat type per season. Ancillary data, such as elevation above sea level, latitude and longitude, average vegetation height, and percent slope inclination, were recorded with a GPS and clinometers per plot. A total of 33 migratory bird species were recorded from the area, of which 20 species were northern (Palearctic) migrants while 13 were inter‐African migrants. There was a significant difference in the mean abundance of migratory bird species between dry and wet seasons (t = 2.13, p = .038, df = 44). The variation in mean abundance per plot between the dry and wet seasons in the grassland habitat was significant (t = 2.35, p = .051, df = 7). In most habitat types during both dry and wet seasons, omnivore birds were the most abundant. While slope was a good predictor for bird species abundance in the dry season, altitude and average vegetation height accounted more in the wet season. The patch of forest and its surrounding is an important bird area for migratory, endemic, and global threatened species. Hence, it is conservation priority area, and the study suggests that conservation coupled with ecotourism development is needed for its sustainability.
Lessons from a decade of lake management: effects of herbicides on Eurasian watermilfoil and native plant communities
Authors: Kujawa Ellen Ruth , Frater Paul , Mikulyuk Alison , Barton Martha , Nault Michelle E. , Van Egeren Scott , Hauxwell Jennifer
Published: April 2017

Eurasian watermilfoil (Myriophyllum spicatum) is a non‐native and invasive aquatic macrophyte with a broad North American distribution. It can have significant negative effects on invaded waterbodies, including decreased native macrophyte diversity, formation of recreational nuisances, and lowered lakefront property values. Previous research suggests that M. spicatum decreases in response to herbicide treatment, but most studies are spatially and temporally limited, usually focusing on a single waterbody for a single year. The long‐term effects of herbicides remain relatively unknown. Here, we share the results of an 11‐yr observational study of aquatic macrophyte diversity, dynamics, and response to herbicide treatment on 28 Wisconsin lakes (15 of which were adaptively managed with herbicide for M. spicatum and 13 of which acted as unmanaged reference lakes). We found that overall, adaptive management decreases M. spicatum abundance over time, but that the efficacy of individual herbicide treatments can vary. We also found that lakes with relatively new M. spicatum populations (discovered within the last decade) treated smaller areas with lower frequency than lakes with established populations, and were able to maintain lower M. spicatum abundance. This suggests that using adaptive, science‐based aquatic plant management strategies, including early detection and response, may increase invasive species management success. Finally, we show that the effect of herbicide treatment on native macrophytes is variable and can be significant. Overall, our results suggest that while herbicide treatment can be an effective adaptive management tool, particularly in lakes with relatively recent M. spicatum invasions, the specific effects of individual treatments can be unpredictable. This study allows lake stakeholders to better understand the efficacy of herbicide treatment, in addition to the possible non‐target effects on native macrophyte species.
Low‐level addition of dissolved organic carbon increases basal ecosystem function in a boreal headwater stream
Authors: Robbins Caleb J. , King Ryan S. , Yeager Alyse D. , Walker Coowe M. , Back Jeffrey A. , Doyle Robert D. , Whigham Dennis F.
Published: April 2017

Comprehension of basic stream ecosystem function relies on an understanding of aquatic–terrestrial linkages. One major component of such linkages is the incorporation of landscape‐derived energy and nutrients into the aquatic food web via microbes. In many boreal streams, wetlands and alder are known to be primary sources of dissolved organic carbon (DOC) and dissolved inorganic nitrogen (DIN), respectively. To simulate the influence of the highly labile portion of wetland‐derived DOC subsidies on microbial production and ecosystem processes in a stream with high landscape‐derived nutrient inputs, we enriched a boreal headwater stream situated in a high‐alder, low‐wetland cover catchment (i.e., high DIN, low DOC) with low levels (~0.25 mg/L) of labile DOC (as acetate‐C) for 9 weeks. We compared nutrient uptake, bacterial biomass production, and photosynthesis of periphyton and ecosystem metabolism in physicochemically similar upstream (reference) and downstream (treatment) reaches. DIN uptake was greater in the treatment than in reference reach on six out of nine dates during the dosing period. Bacterial biomass production positively responded to C enrichment. Ecosystem respiration increased up to ~50% after dosing began. Gross primary production responded positively to DOC enrichment early in the study when riparian vegetation did not limit light availability, but negatively later on in the growing season. We conclude that even low levels of labile DOC may act as a strong subsidy to headwater stream ecosystems, particularly those with high levels of DIN inputs from alder. Headwater streams influenced by high contributions of both alder and wetlands may represent biogeochemical hotspots, and these landscape features should be viewed as vital and complementary in their roles for ecosystem function.
Capital vs. income‐dependent optimal birth date in two North American ungulates
Authors: Hogg John T. , Dunn Stacey J. , Poissant Jocelyn , Pelletier Fanie , Byers John A.
Published: April 2017

Phenotypic plasticity in reproductive traits is of theoretical and applied interest as one avenue by which organisms might maintain an optimal annual reproductive routine in the face of cyclic and/or directional change in environmental conditions. We used long‐term, individual‐based data from parapatric populations of bighorn sheep (Ovis canadensis canadensis) and pronghorn (Antilocapra americana) to evaluate plasticity in breeding date, gestation duration, birth date, birth mass, and fetal growth rate in response to inter‐annual (cyclic) variation in indices of maternal energy income and expense. Traits in both species responded plastically to variation in maternal energy balance. However, despite nearly identical climate and similar vegetative habitat, plasticity was expressed in fundamentally different ways in the study species. Variation in bighorn birth date was primarily due to plasticity in breeding date, whereas variation in pronghorn birth date was primarily due to variation in gestation duration. Across traits, bighorn plastic responses were more consistent with explanations that invoked periodic energy surplus as the basis for plasticity, whereas pronghorn plastic responses were more consistent with explanations that invoked periodic energy deficiency. Later birth date was associated with increased fetal growth rate in bighorn but decreased fetal growth rate in pronghorn. Finally, we detected strong directional selection for early birth among bighorn mothers but found no evidence of selection on pronghorn birth date. Collectively, our results indicate markedly different maternal tactics for timing birth. Bighorn mothers appeared to use stored energy to subsidize the cost of birth prior to the local environmental optimum in an energy‐mediated competition with other females to minimize birth order rank. Pronghorn mothers, committed to high levels of energy allocation to offspring and subject therefore to frequent energy deficiency, timed birth conservatively to more closely match peak reproductive expenditure with peak energy income at the local environmental optimum.
Increased resource availability prevents the disruption of key ecological interactions in disturbed habitats
Authors: Fontúrbel Francisco E. , Salazar Daniela A. , Medel Rodrigo
Published: April 2017

Anthropogenic disturbance can modify habitat structure and resource availability, potentially disrupting ecological interactions. This issue may be critical for pollination and seed dispersal, which determine natural regeneration. The mistletoe Tristerix corymbosus is almost exclusively pollinated by a hummingbird (Sephanoides sephaniodes) and dispersed by a marsupial (Dromiciops gliroides). We examined the extent to which human‐induced habitat change and resource availability influence the interaction rate of this plant–pollinator–seed disperser system, along a forest transformation gradient (from native forest to exotic plantations). We estimated visitation rates of S. sephaniodes and D. gliroides on 70 T. corymbosus mistletoes using camera traps. We related visitation rates to habitat structural features and resource availability (flowers and fruits of the mistletoe and the neighborhood) using spatially explicit models. Sephanoides sephaniodes and D. gliroides visitation rates responded positively to shrub and bamboo cover, moss abundance, and mistletoe spatial arrangement. Pollination and seed dispersal interactions were sensitive to the flower and fleshy‐fruit neighborhoods, being variable across months. Further, D. gliroides showed a non‐random spatial association with fleshy‐fruited plants. A larger sunlight incidence on disturbed habitats may prevent the disruption of key ecological interactions by increasing resource availability. This effect would result from the presence of shade‐intolerant plants, which are benefited by sunlight exposure. Patches of disturbed habitat may enhance landscape heterogeneity, providing complementary resources to the native remnants.
Seasonal resource selection by introduced mountain goats in the southwest Greater Yellowstone Area
Authors: Lowrey B. , Garrott R. A. , Miyasaki H. M. , Fralick G. , Dewey S. R.
Published: April 2017

Mountain goats (Oreamnos americanus) are among the least studied North American ungulates. Aided by successful translocations from the early to mid‐1900s, introduced populations have greatly expanded within non‐native ranges, yet there remains a paucity of empirical studies concerning their habitat requirements and potential distributions. The lack of studies presents a formidable challenge to managers tasked with monitoring mountain goat expansion and mitigating for any potential negative impacts posed to native species and communities. We constructed summer and winter resource selection models using GPS data collected during 2011–2014 from 18 (14 female and four male) mountain goats in the Snake River Range of the southwest Greater Yellowstone Area. We used generalized linear mixed models and evaluated landscape and environmental covariates at multiple spatial grains (i.e., neighborhood analyses within 30‐, 100‐, 500‐, and 1000‐m buffers) within four related suites. The multi‐grain resource selection function greatly improved model fit, indicating that mountain goat resource selection was grain dependent in both seasons. In summer, mountain goats largely selected rugged and steep areas at high elevations and avoided high solar radiation, canopy cover, and time‐integrated normalized difference vegetation index (NDVI). In winter, mountain goats selected lower elevations characterized by steep and rugged slopes on warm aspects and avoided areas with high canopy cover, NDVI amplitude, and snow water equivalent. Slope was the dominant predictor of habitat use in both seasons, although mountain goats selected for steeper slopes in winter than in summer. Regional extrapolations depicted suitable mountain goat habitat in the Snake River, Teton, Gros Ventre, Wyoming, and Salt Ranges centered around steep and rugged areas. Winter range was generally characterized by the steepest slopes within a more broadly distributed and generally less steep summer range. Further research should examine the spatial and temporal overlap with native populations to further our understanding of resource selection dynamics and the potential for introduced mountain goats to alter intraguild behavioral processes of sympatric species, namely the Rocky Mountain bighorn sheep (Ovis canadensis canadensis).
Drought impact on forest regeneration in the SoutheastUSA
Authors: Hu Huifeng , Wang G. Geoff , Bauerle William L. , Klos Ryan J.
Published: April 2017

Elevating concentrations of atmospheric greenhouse gases are now widely acknowledged as a major cause of global warming. A warmer climate could increase the frequency, duration, and/or severity of drought and, in turn, could alter the composition, structure, and biogeography of forests in many regions. To explore the regional effects of different drought severities on forest regeneration, we investigated changes in sapling growth and density across the southeastern United States under various drought and stand conditions using 1991–2005 Forest Health and Monitoring plot data from Alabama, Georgia, and Virginia. Drought effects were examined on three species groups (pine, oak + hickory, and mesophytic species) using the Palmer Drought Severity Index. Stand and site variables, including total basal area, total stand density, tree species richness, slope, and stand age, were used to account for drought effects under varying stand conditions. The oak + hickory and mesophytic species groups exhibited significant reductions in annual growth rate with increasing drought severity. However, no significant difference in annual growth rate was observed within the pine species group. Chi‐square analysis showed that annual mortality rate was significantly dependent on drought severity for each species group but annual recruitment rate was only significantly dependent on drought severity for the oak + hickory group. Total basal area, tree species richness, and stand age had a negative effect on growth in one or more species groups. The observed differential dynamics of sapling growth, mortality, and recruitment among species groups may alter the trend of forest regeneration in southeastern U.S. forests because of the predicted increases in intensity and frequency of droughts in the future. The significant effects of stand conditions on drought responses observed in our study also suggest that appropriate forest management strategies may be useful to maintain structure features of understory saplings for southeastern U.S. forests.
Local microRNA‐133a downregulation is associated with hypertrophy in the dyssynchronous heart
Authors: van Middendorp Lars B. , Kuiper Marion , Munts Chantal , Wouters Philippe , Maessen Jos G. , van Nieuwenhoven Frans A. , Prinzen Frits W.
Published: April 2017

Aims

Left bundle branch block (LBBB) creates considerable regional differences in mechanical load within the left ventricle (LV). We investigated expression of selected microRNAs (miRs) in relation to regional hypertrophy and fibrosis in LBBB hearts and their reversibility upon cardiac resynchronization therapy (CRT).

Methods and results

Eighteen dogs were followed for 4 months after induction of LBBB, 10 of which received CRT after 2 months. Five additional dogs served as control. LV geometric changes were determined by echocardiography and myocardial strain by magnetic resonance imaging tagging. Expression levels of miRs, their target genes: connective tissue growth factor (CTGF), serum response factor (SRF), nuclear factor of activated T cells (NFATc4), and cardiomyocyte diameter and collagen deposition were measured in the septum and LV free wall (LVfw). In LBBB hearts, LVfw and septal systolic circumferential strain were 200% and 50% of control, respectively. This coincided with local hypertrophy in the LVfw. MiR‐133a expression was reduced by 33% in the LVfw, which corresponded with a selective increase of CTGF expression in the LVfw (279% of control). By contrast, no change was observed in SRF and NFATc4 expression was decreased in LBBB hearts. CRT normalized strain patterns and reversed miR‐133a and CTGF expression towards normal, expression of other miRs, related to remodelling, such as miR‐199b and miR‐155f, were not affected.

Conclusions

In the clinically relevant large animal model of LBBB, a close inverse relation exists between local hypertrophy and miR‐133a. Reduced miR‐133a correlated with increased CTGF levels but not with SRF and NFATc4.
One‐Pot Preparation of C1‐Homologated Aliphatic Nitriles from Aldehydes through a Wittig Reaction under Metal‐Cyanide‐Free Conditions
Authors: Ezawa Masatoshi , Togo Hideo
Published: April 2017

A one‐pot protocol to obtain C1‐homologated aliphatic nitriles was achieved by treating aromatic and aliphatic aldehydes with the (methoxymethyl)triphenylphosphonium ylide followed by hydrolysis of the resulting methyl vinyl ethers with pTsOH (Ts = para‐toluenesulfonyl) and treatment with molecular iodine and aqueous ammonia under metal cyanide free conditions. Neopentyl‐type nitriles, which could not be obtained by conventional methods that involved conversion of the neopentyl alcohol into a tosylate and treatment with metal cyanide, were successfully obtained by using the present method.
Stereoselective Construction of Entire Diastereomeric Stereotetrads Based on an Asymmetric Morita–Baylis–Hillman Reaction
Authors: Yoshimura Hikaru , Ishihara Jun , Hatakeyama Susumi
Published: April 2017

A method for the enantio‐ and diastereoselective construction of all possible stereoisomers of a polypropionate stereotetrad having four contiguous stereogenic centers has been developed. The approach features an iterative sequence of cinchona‐alkaloid‐catalyzed Morita–Baylis–Hillman reaction and subsequent diastereoselective hydrogenation. By this method, benzaldehyde was successfully converted into eight diastereoisomeric 3,5‐dihydroxy‐2,4‐dimethyl‐5‐phenylpentanoic acid ester derivatives with high enantiomeric purities (99 % ee) in 25–67 % overall yield (eight steps) in a reagent‐controlled manner.
Bioelectrochemical Systems for Measuring Microbial Cellular Functions
Authors: Selim Hend M. M. , Kamal Ahmed M. , Ali Dina M. M. , Hassan Rabeay Y. A.
Published: April 2017

In bioelectrochemical systems (BESs), living microorganisms are capable of converting the chemical energy of degradable organic matters into bioelectricity. The electrical current outputs are dependent on the microbial cell viability and the biodegradation rates. Therefore, monitoring the current generative through the BES is promising for the microbial activity assessments. As compared to conventional microbiological methods, BESs are considered as non‐invasive techniques that offer rapid and sensitive detection of cellular functions (extra‐ and/or intracellular). Therefore, several progressions were made in the last 100 years in order to develop effective BESs. In this review, the involvements of materials sciences, microbiology, and electrochemistry in the effective designing and developments of BESs were intensively discussed. Due to the nanotechnology revolutions, manipulation of electrode materials led to the creation of different BES generations. Therefore, the impact of nanomaterials on the developments of the second and third generations of BESs is still the outlook of this promising research area.
BiVO4/Mn3O4 a novel p–n heterojunction photocatalyst functionalized with metalloporphyrins: Synthesis, charge transfer mechanism, and enhanced visible‐light photocatalysis for degradation of dye pollutant
Authors: Rahimi Rahmatollah , Mehrehjedy Amin , Zargari Solmaz
Published: April 2017

A simple one‐pot hydrothermal method was successfully used to synthesize p–n heterojunction Mn3O4/BiVO4 composites with different contents of BiVO4. The experimental results show that the as‐prepared p–n heterojunction Mn3O4/BiVO4 composite exhibited higher visible light photocatalytic activity for the degradation of model dye methylene blue than the pure BiVO4 and Mn3O4 crystal under irradiation of 5 W white LED lamp. The enhanced photocatalytic efficiency is due to a large number of p–n heterojunctions in Mn3O4/BiVO4 composites, which effectively reduces the recombination of the electrons and holes by charge transfer from n‐type BiVO4 to p‐type Mn3O4 crystals. The prepared p–n heterojunction Mn3O4/BiVO4 composite was functionalized with cobalt, zinc, copper, and tin complexes of porphyrin. The energy diagrams of these prepared compounds were calculated via the electrochemical investigations and the electron transfer mechanism was discussed in details. The photocatalytic efficiency of the functionalized nanocomposites enhances significantly compared to the p–n heterojunction Mn3O4/BiVO4 under visible light irradiation. Between the prepared compounds, BiVO4/Mn3O4‐CoTCPP shows higher photocatalytic activity. This compound can destruct 98% of dye pollutant in 180 min under irradiation of 5 W white LED lamp. Furthermore, this photocatalyst shows proper stability after four cycle degradation test. © 2017 American Institute of Chemical Engineers Environ Prog, 36: 1439–1448, 2017
High‐frequency oscillations detected in ECoG recordings correlate with cavernous malformation and seizure‐free outcome in a child with focal epilepsy: A case report
Authors: Liu Su , Quach Michael M. , Curry Daniel J. , Ummat Monika , Seto Elaine , Ince Nuri F.
Published: April 2017

Epilepsy associated with cavernous malformation (CM) often requires surgical resection of seizure focus to achieve seizure‐free outcome. High‐frequency oscillations (HFOs) in intracranial electroencephalogram (EEG) are reported as potential biomarkers of epileptogenic regions, but to our knowledge there are no data on the existence of HFOs in CM‐caused epilepsy. Here we report our experience of the identification of the seizure focus in a 3‐year‐old pediatric patient with intractable epilepsy associated with CM. The electrocorticographic recordings were obtained from a 64‐contact grid over 2 days in the epilepsy monitoring unit (EMU). The spatial distribution of HFOs and epileptic spikes were estimated from recording segments right after the electrode placement, during sleep and awake states separately. The HFO distribution showed consistency with the perilesional region; the location of spikes varied over days and did not correlate with the lesion. The HFO spatial distribution was more compact in sleep state and pinpointed the contacts sitting on the CM border. Following the resection of the CM and the hemosiderin ring, the patient became seizure‐free. This is the first report describing HFOs in a pediatric patient with intractable epilepsy associated with CM and shows their potential in identifying the seizure focus.
Distinct prognostic roles and heterogeneity of TTF1 copy number and TTF1 protein expression in non‐small cell lung cancer
Authors: Yoshimura Katsuhiro , Inoue Yusuke , Mori Kazutaka , Iwashita Yuji , Kahyo Tomoaki , Kawase Akikazu , Tanahashi Masayuki , Ogawa Hiroshi , Inui Naoki , Funai Kazuhito , Shinmura Kazuya , Niwa Hiroshi , Suda Takafumi , Sugimura Haruhiko
Published: April 2017

Thyroid transcription factor 1 (TTF1) located on chromosome band 14q13.3 is an oncogene and a suppressor gene in non‐small cell lung cancer (NSCLC). The prognostic relevance of TTF1 copy number alterations (CNAs) and their association with TTF1 protein expression are poorly understood. Here, we assessed TTF1 CNAs and protein expression using microarrays in a cohort of 636 NSCLC, including 423 adenocarcinoma (ADC) and 171 squamous cell carcinoma (SCC). In addition, fluorescent in situ hybridization and immunohistochemistry were performed. TTF1 CNAs were detected in 23% of NSCLC (23% of ADC and 20% of SCC). Specifically, TTF1 amplification and polysomy were observed in 5% and 18% of NSCLC, and in 7% and 16% of ADC, respectively. TTF1 expression was detected in 85% of ADC. TTF1 CNAs were significantly associated with advanced tumor stage, EGFR mutations, and TTF1 expression. A multivariate Cox hazards model analysis of overall survival and recurrence‐free survival demonstrated that both TTF1 amplification and polysomy were independent indicators of an unfavorable prognosis in patients with NSCLC. Survival was inversely correlated with TTF1 copy number. In contrast, TTF1 protein expression was an independent favorable prognostic factor. Intratumoral and intertumoral heterogeneities of TTF1 CNAs and TTF1 protein expression were assessed using primary cores from 138 pairs of primary tumors and corresponding nodal metastases. The concordance rate for TTF1 CNAs and TTF1 protein expression was high within tumors and between primary and metastatic tumors. Altogether, these results suggest that TTF1 CNAs are correlated with TTF1 protein expression, but have opposing effects on survival.
Experience with the TBM drive through clay rocks with low strength in the Boßler Tunnel
Authors: Voringer Jürgen , Zenz Reinhard , Meyer Anna‐Maria , Strauss Armin , Hofmann Arno
Published: April 2017

The Tunnel Albaufstieg consortium won the contract with an alternative proposal to drive a section about 2.8 km long of the 8.8 km long Boßler Tunnel with a tunnel boring machine (TBM). The next section, where squeezing conditions were forecast, was to be tunnelled by the shotcrete method according to the tender documents. Manifold and extensive additional investigations delivered the basis for the extension of the TBM drive along the entire length of the Boßler Tunnels. The driving of the section through the Aalenian 1 geology was problem free due to the low strengths and good cuttability of the rock mass combined with its impermeability. The next section in the intercalation of claystone and sandstone of the Aalenian 2 was much more differentiated but managable. The breakthrough of the east bore of the Boßler Tunnel confirms to the responsible people for the client and contractor that the decision to follow the aim of consistent mechanised tunnelling had been correct.
The technical solution for working beneath the protected DB directorate building on the major Stuttgart 21 project
Authors: Vardijan Tomas , Pradel Michael
Published: April 2017

Built in 1914, the listed Reichsbahn directorate building was formerly used as an administrative building by Deutsche Bahn AG in Stuttgart. The Stuttgart 21 Project requires new tracks from the Feuerbach and Bad Cannstatt Tunnels to be built, which branch off from 4 to 8 tracks in the area beneath the DB directorate. Complete demolition of the directorate building was not possible due to the objection of the listed monument authorities, the city administration, the municipal council of architects and the former building owner Vivico. In view of this the preservation of the main building was specified in the planning decision of 28/01/2005.

In order for the new station to be constructed by cut‐and‐cover, part of the building had to be secured and underpinned. The design should also take into account two single‐track underground rail tunnels beneath the building and newly constructed temporary retaining structures. The temporary works required to distribute the building loads extended over an area of 800 m2, around half of the building footprint, and poses particular constraints on the design and construction approach due to the building preservation order and its inner city proximity.
Thriving in relation to cognitive impairment and neuropsychiatric symptoms in Swedish nursing home residents
Authors: Björk Sabine , Lövheim Hugo , Lindkvist Marie , Wimo Anders , Edvardsson David
Published: April 2017

Objectives

The purpose of this study was to explore relations among thriving, cognitive function, and neuropsychiatric symptoms (NPS) in nursing home residents.

Methods

A national, cross‐sectional, randomized study of Swedish nursing home residents (N = 4831) was conducted between November 2013 and September 2014. Activities of daily life functioning, cognitive functioning, NPS, and thriving were assessed with the Katz activities of daily living, Gottfries' Cognitive Scale, Nursing Home version of the Neuropsychiatric Inventory, and Thriving of Older People Scale, respectively. Individual NPS were explored in relation to cognitive function. Simple linear and multiple regression models were used to explore thriving in relation to resident characteristics.

Results

Aggression and depressive symptoms were identified as negatively associated with thriving regardless of resident cognitive functioning. At higher levels of cognitive functioning, several factors showed associations with thriving; however, at lower levels of cognitive functioning, only the degree of cognitive impairment and the NPS was associated with thriving. Most of the individual NPS formed nonlinear relationships with cognitive functioning with higher symptom scores in the middle stages of cognitive functioning. Exceptions were elation/euphoria and apathy, which increased linearly with severity of cognitive impairment.

Conclusions

The lower the cognitive functioning was, the fewer factors were associated with thriving. Aggression and depressive symptoms may indicate lower levels of thriving; thus, targeting these symptoms should be a priority in nursing homes. Copyright © 2017 John Wiley & Sons, Ltd.
Association between serotonin denervation and resting‐state functional connectivity in mild cognitive impairment
Authors: Barrett Frederick S. , Workman Clifford I. , Sair Haris I. , Savonenko Alena V. , Kraut Michael A. , Sodums Devin J. , Joo Jin J. , Nassery Najlla , Marano Christopher M. , Munro Cynthia A. , Brandt Jason , Zhou Yun , Wong Dean F. , Smith Gwenn S.
Published: April 2017

Resting‐state functional connectivity alterations have been demonstrated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) before the observation of AD neuropathology, but mechanisms driving these changes are not well understood. Serotonin neurodegeneration has been observed in MCI and AD and is associated with cognitive deficits and neuropsychiatric symptoms, but the role of the serotonin system in relation to brain network dysfunction has not been a major focus of investigation. The current study investigated the relationship between serotonin transporter availability (SERT; measured using positron emission tomography) and brain network functional connectivity (measured using resting‐state functional MRI) in 20 participants with MCI and 21 healthy controls. Two SERT regions of interest were selected for the analysis: the Dorsal Raphe Nuclei (DRN) and the precuneus which represent the cell bodies of origin and a cortical target of projections of the serotonin system, respectively. Both regions show decreased SERT in MCI compared to controls and are the site of early AD pathology. Average resting‐state functional connectivity did not differ between MCI and controls. Decreased SERT in DRN was associated with lower hippocampal resting‐state connectivity in MCI participants compared to controls. Decreased SERT in the right precuneus was also associated with lower resting‐state connectivity of the retrosplenial cortex to the dorsal lateral prefrontal cortex and higher resting‐state connectivity of the retrosplenial cortex to the posterior cingulate and in patients with MCI but not in controls. These results suggest that a serotonergic mechanism may underlie changes in brain functional connectivity in MCI. Hum Brain Mapp 38:3391–3401, 2017. © 2017 Wiley Periodicals, Inc.
Neural mechanisms underlying the reward‐related enhancement of motivation when remembering episodic memories with high difficulty
Authors: Shigemune Yayoi , Tsukiura Takashi , Nouchi Rui , Kambara Toshimune , Kawashima Ryuta
Published: April 2017

The motivation to receive rewards enhances episodic memories, and the motivation is modulated by task difficulty. In episodic retrieval, however, functional neuroimaging evidence regarding the motivation that mediates interactions between reward and task difficulty is scarce. The present fMRI study investigated this issue. During encoding performed without fMRI, participants encoded Japanese words using either deep or shallow strategies, which led to variation in difficulty level during subsequent retrieval. During retrieval with fMRI, participants recognized the target words in either high or low monetary reward conditions. In the behavioral results, a reward‐related enhancement of memory was found only when the memory retrieval was difficult, and the rewarding effect on subjective motivation was greater in the retrieval of memories with high difficulty than those with low difficulty. The fMRI data showed that reward‐related increases in the activation of the substantia nigra/ventral tegmental area (SN/VTA), medial temporal lobe (MTL), dorsomedial prefrontal cortex (dmPFC), and dorsolateral prefrontal cortex (dlPFC) were greater during the retrieval of memories with high difficulty than those with low difficulty. Furthermore, reward‐related enhancement of functional connectivity between the SN/VTA and MTL and between the SN/VTA and dmPFC during the retrieval of memories with high difficulty was significantly correlated with reward‐related increases of retrieval accuracy and subjective motivation. The reward‐related enhancement of episodic retrieval and retrieval‐related motivation could be most effective when the level of retrieval difficulty is optimized. Such reward‐related enhancement of memory and motivation could be modulated by a network including the reward‐related SN/VTA, motivation‐related dmPFC, and memory‐related MTL.Hum Brain Mapp 38:3428–3443, 2017. ©2017 Wiley Periodicals, Inc.
Involvement of intracellular Zn2+ signaling in LTP at perforant pathway–CA1 pyramidal cell synapse
Authors: Tamano Haruna , Nishio Ryusuke , Takeda Atsushi
Published: April 2017

Physiological significance of synaptic Zn2+ signaling was examined at perforant pathway–CA1 pyramidal cell synapses. In vivo long‐term potentiation (LTP) at perforant pathway–CA1 pyramidal cell synapses was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. Perforant pathway LTP was not attenuated under perfusion with CaEDTA (10 mM), an extracellular Zn2+ chelator, but attenuated under perfusion with ZnAF‐2DA (50 μM), an intracellular Zn2+ chelator, suggesting that intracellular Zn2+ signaling is required for perforant pathway LTP. Even in rat brain slices bathed in CaEDTA in ACSF, intracellular Zn2+ level, which was measured with intracellular ZnAF‐2, was increased in the stratum lacunosum‐moleculare where perforant pathway–CA1 pyramidal cell synapses were contained after tetanic stimulation. These results suggest that intracellular Zn2+ signaling, which originates in internal stores/proteins, is involved in LTP at perforant pathway–CA1 pyramidal cell synapses. Because the influx of extracellular Zn2+, which originates in presynaptic Zn2+ release, is involved in LTP at Schaffer collateral‐CA1 pyramidal cell synapses, synapse‐dependent Zn2+ dynamics may be involved in plasticity of postsynaptic CA1 pyramidal cells.
An Exploration of Differences in Content and Processes Underlying Reflection on Challenging Experiences at Work
Authors: Maurer Todd J. , Leheta Dina M. , Conklin Thomas A.
Published: April 2017

While the use of structured reflection in some form is common in management, education, the military, and health care, little is known about existing differences in reflection. We collected exploratory data around the nature of differences in the content and process of reflection. By asking management students about their reflections on challenging work experiences, we focused this conversation at the intersection of workplace behavior and education, a high‐value space for discovery by scholars and educators in human resource development. Respondents participated in surveys and interviews that asked about the types of experiences at work they reflect upon and why; how they reflect including the mode, content, and process of their reflections; and the consequences or outcomes of their reflections. We present detailed data on the observed differences, which suggest that there may be multiple distinctions underlying the notion of reflection and that such differences are not systematically and meaningfully addressed in theory, research, or practice. We also offer a framework to help scholars, instructors, coaches, and students more readily explore variations in reflection tendencies and to pursue the possible meaning of these variations for research and practice.
Misoprostol use for second‐trimester termination of pregnancy among women with one or more previous cesarean deliveries
Authors: Cuellar Torriente Martin , Steinberg Wilhelm J. , Joubert Gina
Published: April 2017

Objective

To establish the safety and efficacy of misoprostol for second‐trimester termination of pregnancy among women with one or more previous cesarean deliveries.

Methods

In a retrospective study, data were reviewed from women attending a reproductive health clinic in Bloemfontein, South Africa, for second‐trimester termination between 2010 and 2013. The study group, comprising women with one or more previous cesareans, was compared with a control group, comprising women with no previous cesarean or uterine scarring. Procedure‐specific information was compared, including misoprostol use, termination duration, need for other methods (e.g. oxytocin), placenta delivery, termination outcome, and bleeding.

Results

The study group comprised 268 women: 231 (86.2%) with one and 37 (13.8%) with two previous cesareans. The control group comprised 266 women. Incomplete abortion was recorded in 223 (85.4%) of 261 women in the study group and 213 (80.4%) of 265 in the control group. The number of women with retained placenta was higher in the study than in the control group (158/261 [60.5%] vs 146/265 [55.1%]; P<0.001). Severe bleeding was observed only in the control group (7/266 [2.6%]). No uterine rupture was observed.

Conclusion

Misoprostol was safe for second‐trimester termination among women with previous cesareans; however, the efficacy of the local regimen was reduced owing to high placental retention.
RNA sensors of the innate immune system and their detection of pathogens
Authors: Chen Nanhua , Xia Pengpeng , Li Shuangjie , Zhang Tangjie , Wang Tony T. , Zhu Jianzhong
Published: April 2017

The innate immune system plays a critical role in pathogen recognition and initiation of protective immune response through the recognition of pathogen associated molecular patterns (PAMPs) by its pattern recognition receptors (PRRs). Nucleic acids including RNA and DNA have been recognized as very important PAMPs of pathogens especially for viruses. RNA are the major PAMPs of RNA viruses, to which most severe disease causing viruses belong thus posing a tougher challenge to human and animal health. Therefore, the understanding of the immune biology of RNA PRRs is critical for control of pathogen infections especially for RNA virus infections. RNA PRRs are comprised of TLR3, TLR7, TLR8, RIG‐I, MDA5, NLRP3, NOD2, and some other minorities. This review introduces these RNA PRRs by describing the cellular localizations, ligand recognitions, activation mechanisms, cell signaling pathways, and recognition of pathogens; the cross‐talks between various RNA PRRs are also reviewed. The deep insights of these RNA PRRs can be utilized to improve anti‐viral immune response. © 2017 IUBMB Life, 69(5):297–304, 2017
Insulin regulates Bbs4 during adipogenesis
Authors: Nahum Netta , Forti Efrat , Aksanov Olga , Birk Ruth
Published: April 2017

Bardet‐Biedl syndrome (BBS) is a pleiotropic autosomal recessive disorder associated with marked obesity, increased susceptibility to insulin resistance and type 2 diabetes. However, it is unknown whether the link between BBS and diabetes is indirect or direct. Adipogenesis and adipocyte function are regulated by hormonal stimuli, with insulin and insulin growth factor (IGF) playing an important role both in normal and impaired conditions. We have previously shown augmented transcript levels of BBS genes upon induction of adipogenesis. The aim of this study was to investigate the role of insulin in BBS. Through in vitro studies in adipocytes in which Bbs4 expression was either silenced (SiBbs4) or overexpressed (OEBbs4), we showed that insulin and IGF dose‐ and time‐dependently decrease transcription and protein expression of BBS genes during adipogenesis. Silencing of Bbs4 expression in adipocytes significantly impaired and reduced glucose uptake. This effect was reversed by Bbs4 overexpression. Inhibition of PI 3‐kinase resulted in upregulation of Bbs transcripts, suggesting that the PI3K pathway is involved in the regulation of these genes. In conclusion, we showed that insulin is a direct regulator of Bbs1, 2, 4 and 6. This hormonal regulation might indicate a metabolic link of these genes to obesity and metabolic syndrome. © 2017 IUBMB Life, 69(7):489–499, 2017
The stiffness of a crosslinked hyaluronan hydrogel affects its chondro‐induction activity on hADSCs
Authors: Teong Benjamin , Wu Shun‐Cheng , Chang Chien‐Mei , Chen Jhen‐Wei , Chen Hui‐Ting , Chen Chung‐Hwan , Chang Je‐Ken , Ho Mei‐Ling
Published: April 2017

Matrix stiffness plays an important role in stem cell differentiation. This study reports the synthesis of methacrylated hyaluronan (MeHA) with different degrees of methacrylation, ranging from 15 to 140% per disaccharide unit, which corresponds to a matrix stiffness ranging from 1.5 to 8 KPa. The swelling ratio was inversely proportional to the matrix stiffness, but the water content remained constant at >97% of the hydrogel mass. A fibril‐like surface morphology and larger pore size were observed in lyophilized MeHA hydrogel with a lower stiffness. The matrix stiffness also affected the degradability of the MeHA hydrogel, where softer MeHA hydrogels (MeHA15 and MeHA30) were completely degraded within 6 days and a stiffer MeHA hydrogel (MeHA140) was able to retain ∼25% of its initial mass after 30 days. Subsequently, the crosslinked MeHA hydrogel was used as a scaffold to encapsulate human adipose‐derived stem cells (hADSCs). The embedded cells remained viable and expressed ∼11‐fold higher levels of aggrecan and 42‐fold higher levels of collagen type II in MeHA140 compared with ADSCs cultured in HA‐coated wells. In addition, cells grown in MeHA140 exhibited the highest rates of glycosaminoglycan and collagen type II synthesis of ∼5 ng/DNA and 0.4 ng/DNA, respectively. Immunofluorescence staining showed an increase of collagen type II synthesis in MeHA65, MeHA85 and MeHA140. This study showed that the matrix stiffness of a hydrogel can be modulated by the degree of methacrylation, thus affecting the efficacy of chondrogenesis in hADSCs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 808–816, 2018.