julilili42/papers huggingface dataset:
A Simulation Study Comparing Recent Approaches for the Estimation of Nonlinear Effects in SEM Under the Condition of Nonnormality
2014-04-03

In the past decade new approaches for the estimation of latent nonlinear interaction and quadratic effects in structural equation modeling have been proposed (Kelava & Brandt, 2009; Klein & Moosbrugger, 2000; Klein & Muthén, 2007; Marsh, Wen, & Hau, 2004; Mooijaart & Bentler, 2010; Wall & Amemiya, 2003). Most approaches have been developed for the analysis of normally distributed latent predictor variables. In this article, we investigate the performance of five recent approaches under the condition of nonnormally distributed data: the extended unconstrained approach (Kelava & Brandt, 2009), LMS (Klein & Moosbrugger, 2000), QML (Klein & Muthén, 2007), the 2SMM approach (Wall & Amemiya, 2003), and the method of moments approach by Mooijaart and Bentler (2010). Advantages and limitations of the approaches are discussed.
Unusual commensurability effects in quasiperiodic pinning arrays induced by local inhomogeneities of the pinning site density
2014-04-03

We experimentally investigate the magnetic field dependence of the critical current Ic(B) of superconducting niobium thin films patterned with periodic and quasiperiodic antidot arrays on the submicron scale. For this purpose we monitor current–voltage characteristics at different values of B and temperature T. We investigate samples with antidots positioned at the vertices of two different tilings with quasiperiodic symmetry, namely the Shield Tiling and the Tuebingen Triangle Tiling. For reference we investigate a sample with a triangular antidot lattice. We find modulations of the critical current for both quasiperiodic tilings, which have partly been predicted by numerical simulations but not observed in experiments yet. The particularity of these commensurability effects is that they correspond to magnetic field values slightly above an integer multiple of the matching field. The observed matching effects can be explained by the caging of interstitial vortices in quasiperiodically distributed cages and the formation of symmetry-induced giant vortices.
The fossil land and freshwater snails of Gündlkofen (Middle Miocene, Germany)
2014-04-03

The molluscan fauna from the Middle Miocene (MN 5–6) fossil site of Gündlkofen in southern Germany was first reported by Gall (1980: Mitt. Bayer. Staatssaml. Paläont. hist. Geol., 20, 51–77). He listed 34 continental gastropod species, which were neither figured nor properly described in many cases. Here a revision of his identifications is presented, with a full description of the material and illustration of the best preserved specimens. Following this revision, 20 species are listed for Gündlkofen. Unfortunately, part of the original material was missing and the record of a few species could not be confirmed. The depositional environment seems to have been a temporary water body, like an oxbow lake, surrounded by a humid and warm forest and scrubland.
Upregulation of the large conductance voltage- and Ca2+-activated K+ channels by Janus kinase 2
2014-04-03

The iberiotoxin-sensitive large conductance voltage- and Ca 2+ -activated potassium (BK) channels (maxi-K + -channels) hyperpolarize the cell membrane thus supporting Ca 2+ entry through Ca 2+ -release activated Ca 2+ channels. Janus kinase-2 (JAK2) has been identified as novel regulator of ion transport. To explore whether JAK2 participates in the regulation of BK channels, cRNA encoding Ca 2+ -insensitive BK channels (BK M513I+Δ899–903 ) was injected into Xenopus oocytes with or without cRNA encoding wild-type JAK2, gain-of-function V617F JAK2, or inactive K882E JAK2. K + conductance was determined by dual electrode voltage clamp and BK-channel protein abundance by confocal microscopy. In A204 alveolar rhabdomyosarcoma cells, iberiotoxin-sensitive K + current was determined utilizing whole cell patch clamp. A204 cells were further transfected with JAK2 and BK-channel transcript, and protein abundance was quantified by RT-PCR and Western blotting, respectively. As a result, the K + current in BK M513I+Δ899–903 -expressing oocytes was significantly increased following coexpression of JAK2 or V617F JAK2 but not K882E JAK2. Coexpression of the BK channel with V617F JAK2 but not K882E JAK2 enhanced BK-channel protein abundance in the oocyte cell membrane. Exposure of BK-channel and V617F JAK2-expressing oocytes to the JAK2 inhibitor AG490 (40 μM) significantly decreased K + current. Inhibition of channel insertion by brefeldin A (5 μM) decreased the K + current to a similar extent in oocytes expressing the BK channel alone and in oocytes expressing the BK channel and V617F JAK2. The iberiotoxin (50 nM)-sensitive K + current in rhabdomyosarcoma cells was significantly decreased by AG490 pretreatment (40 μM, 12 h). Moreover, overexpression of JAK2 in A204 cells significantly enhanced BK channel mRNA and protein abundance. In conclusion, JAK2 upregulates BK channels by increasing channel protein abundance in the cell membrane.
The outcome of shared pollination services is affected by the density and spatial pattern of an attractive neighbour
2014-04-04

Summary Interactions among neighbouring plants are often mediated by foraging choices of pollinators. For example, the presence of a conspicuous species may increase the number of pollinators attracted to its vicinity, indirectly increasing visitation rates also to neighbouring plants. Because pollinator choices are frequently density‐dependent, the presence of a conspicuous species at high densities may also increase competition for pollination services. Additionally, models predict that plant density will interact with spatial distribution in manipulating the pollinator behaviour, yet experimental evidence for this effect is missing. We performed a field experiment in which we introduced a highly conspicuous species in different densities and spatial configurations in a full‐factorial manner into a species‐rich meadow and studied its effect on neighbouring plants. We showed that the highly conspicuous species strongly contributed to the attractiveness of its local patch and thus benefited its neighbours. However, because of the strong density effect, the conspicuous species changed its role and became a competitor for pollinators when its density increased. We supported our theoretical assumptions and showed that when the introduced conspicuous species was regularly distributed among other plants in the patch, it increased visitation rate, and in some cases also seed set, to conspicuous neighbours relative to when it was aggregated, at least at low densities. Synthesis . We suggest that complex interactions between density and spatial distribution of plant species at the patch scale are highly relevant for the interpretation of pollinator behaviour and therefore should be treated as factors of floral attractiveness in future studies.
Lower Cretaceous (Hauterivian-Albian) ammonite biostratigraphy in the Maestrat Basin (E Spain)
2014-04-04

A review of the stratigraphic distribution of ammonoid species in the Lower Cretaceous (Hauterivian-Albian) of the Maestrat Basin (E Spain) was carried out. The specimens were mainly collected in the field by us and are stored in university or museum collections. Specimens from private collections and figured in the literature were also studied. We recognized 73 species that are distributed, in accordance with the latest version of the standard Mediterranean ammonite zonation for the Lower Cretaceous, in 14 ammonite zones: Acanthodiscus radiatus, Crioceratites loryi, Lyticoceras nodosoplicatum (Lower Hauterivian); Pseudothurmannia ohmi (Upper Hauterivian); Imerites giraudi (Upper Barremian); Deshayesites oglanlensis, Deshayesites forbesi, Deshayesites deshayesi, Dufrenoyia furcata (Lower Aptian); Epicheloniceras martini, Parahoplites melchioris, Acanthohoplites nolani (Upper Aptian); Leymeriella tardefurcata and Douvilleiceras mammillatum (Lower Albian). The recognition of these biozones allows a precise age calibration of the Maestrat Basin's lithostatigraphic units that contain ammonoids as well as an associated indirect age calibration of the formations without ammonoids. Consequently, this report provides an updated, comprehensive and precise biostratigraphic framework, which aims to become a reference for the analysis of the Lower Cretaceous strata of the Maestrat Basin. The results are also relevant for the analysis of coeval ammonite-bearing sedimentary successions found in other Tethyan basins.
Assessing cisplatin-induced ototoxicity and otoprotection in whole organ culture of the mouse inner ear in simulated microgravity
2014-04-05

Cisplatin is a widely used anti-cancer drug. Ototoxicity is a major dose-limiting side-effect. A reproducible mammalian in-vitro model of cisplatin ototoxicity is required to screen and validate otoprotective drug candidates. We utilized a whole organ culture system of the postnatal mouse inner ear in a rotating wall vessel bioreactor under "simulated microgravity" culture conditions. As previously described this system allows whole organ culture of the inner ear and quantitative assessment of ototoxic effects of aminoglycoside induced hair cell loss. Here we demonstrate that this model is also applicable to the assessment of cisplatin induced ototoxicity. In this model cisplatin induced hair cell loss was dose and time dependent. Increasing exposure time of cisplatin led to decreasing EC50 concentrations. Outer hair cells were more susceptible than inner hair cells, and hair cells in the cochlear base were more susceptible than hair cells in the cochlear apex. Initial cisplatin dose determined the final extent of hair cell loss irrespective if the drug was withdrawn or continued. Dose dependant otoprotection was demonstrated by co-administration of the antioxidant agent N-acetyl l-cysteine. The results support the use of this inner ear organ culture system as an in vitro assay and validation platform for inner ear toxicology and the search for otoprotective compounds.
Assessment of an Advanced Image-Based Technique to Calculate Virtual Monoenergetic Computed Tomographic Images From a Dual-Energy Examination to Improve Contrast-To-Noise Ratio in Examinations Using Iodinated Contrast Media
2014-04-07

With regard to optimized iodine CNR, it is more efficient to perform dual-energy scans and compute virtual monoenergetic images at 40 keV using the Mono+ technique than to perform low kilovolt scans. Given the improved CNR, the Mono+ algorithm could be very useful in improving both detection and differential diagnosis of abdominal lesions, specifically low-contrast lesions, as well as in other anatomical regions where improved iodine CNR is beneficial.
Effect of Metformin on Methylglyoxal Metabolism in Patients with Type 2 Diabetes
2014-04-07

The effect of metformin on methylglyoxal (MG) metabolism was studied in a prospective non-randomized 24 weeks trial in patients with type 2 diabetes.Metformin treatment, in addition to life style intervention, significantly reduced morning glucose and HbA1c whilst body weight and BMI were only marginally reduced during the 24 week trial. Treatment significantly reduced both plasma MG and carboxymethyl-lysine (CML), a marker of oxidative stress. The reduction in MG was paralleled by a significant increase in the activity of Glyoxalase 1 (Glo1), the major route of MG detoxification, in peripheral blood mononuclear cells and red blood cells. Multivariate analysis showed that the changes in MG were dependent upon the metformin treatment.This study supports previous findings that metformin can reduce plasma MG in type 2 diabetic patients. However, given the observed increase in Glo1 activity, this reduction is due not only to the scavenging properties of metformin, but the restoration of Glo1 activity.
Delivery of endocytosed proteins to the cell–division plane requires change of pathway from recycling to secretion
2014-04-08

Membrane trafficking is essential to fundamental processes in eukaryotic life, including cell growth and division. In plant cytokinesis, post-Golgi trafficking mediates a massive flow of vesicles that form the partitioning membrane but its regulation remains poorly understood. Here, we identify functionally redundant Arabidopsis ARF guanine-nucleotide exchange factors (ARF-GEFs) BIG1–BIG4 as regulators of post-Golgi trafficking, mediating late secretion from the trans-Golgi network but not recycling of endocytosed proteins to the plasma membrane, although the TGN also functions as an early endosome in plants. In contrast, BIG1-4 are absolutely required for trafficking of both endocytosed and newly synthesized proteins to the cell–division plane during cytokinesis, counteracting recycling to the plasma membrane. This change from recycling to secretory trafficking pathway mediated by ARF-GEFs confers specificity of cargo delivery to the division plane and might thus ensure that the partitioning membrane is completed on time in the absence of a cytokinesis-interphase checkpoint.
Investigation of a Calcium-Responsive Contrast Agent in Cellular Model Systems: Feasibility for Use as a Smart Molecular Probe in Functional MRI
2014-04-08

Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca(2+) may allow tracking neuronal activity independent of brain vasculature, thus avoiding the characteristic limitations of current fMRI techniques. Here we report an in vitro proof-of-principle study with a Ca(2+)-sensitive, Gd(3+)-based SCA in an attempt to validate its potential use as a functional in vivo marker. First, we quantified its relaxometric response in a complex 3D cell culture model. Subsequently, we examined potential changes in the functionality of primary glial cells following administration of this SCA. Monitoring intracellular Ca(2+) showed that, despite a reduction in the Ca(2+) level, transport of Ca(2+) through the plasma membrane remained unaffected, while stimulation with ATP induced Ca(2+)-transients suggested normal cellular signaling in the presence of low millimolar SCA concentrations. SCAs merely lowered the intracellular Ca(2+) level. Finally, we estimated the longitudinal relaxation times (T1) for an idealized in vivo fMRI experiment with SCA, for extracellular Ca(2+) concentration level changes expected during intense neuronal activity which takes place upon repetitive stimulation. The values we obtained indicate changes in T1 of around 1-6%, sufficient to be robustly detectable using modern MRI methods in high field scanners. Our results encourage further attempts to develop even more potent SCAs and appropriate fMRI protocols. This would result in novel methods that allow monitoring of essential physiological processes at the cellular and molecular level.
Mutations in PNPLA6 Cause a Range of Neurodegenerative Phenotypes (P6.060)
2014-04-08

OBJECTIVE: Exome sequencing has provided the platform to investigate the genetic causes of many Mendelian disorders and in many cases has expanded the clinical phenotypes associated with particular gene defects. BACKGROUND: Boucher-Neuhäuser syndrome (BNS) is a rare autosomal recessive disorder characterized by spinocerebellar ataxia, chorioretinal dystrophy, and a failure of the pituitary to stimulate gonadal development during puberty. Similar to many rare Mendelian disorders, the underlying mutations that give rise to BNS remain unknown. DESIGN/METHODS: To this end, we performed exome sequencing on 10 BNS-families. All sequencing results were imported and analyzed by the GEnomes Management Application (GEM.app). RESULTS: In a subset of the families (3 out of 10), we identified rare, conserved, and damaging mutations in PNPLA6 that co-segregated with disease. Previously, mutations in PNPLA6 were described to cause complicated spastic paraplegia (cHSP) in two families. Therefore we explored the possibility of a spectrum of neurodegeneration caused by alterations in PNPLA6. We identified a cHSP family, a spastic ataxia family, and a Holmes syndrome family with compound heterozygous mutations in PNPLA6. In total we report 6 families with homozygous or compound heterozygous mutations in PNPLA6. The majority of mutations clustered on the C-terminal catalytic domain, which has been shown to have esterase activity and phospholipase activity for lysophosphatidylcholine (LPC) and phosphatidylcholine (PC). Alteration of phospholipid metabolism has been shown to impact mitochondrial function, which is hypothesized to be critical for the functions of the long axons of the corticospinal tracts. Recently, several genes (DDHD1, DDHD2, CYP2U1), have highlighted the importance of phospholipase enzyme activity in neurodegeneration. CONCLUSIONS: Our findings show that Boucher-Neuhäuser Syndrome and Holmes' Syndrome can be caused by mutations in PNPLA6, and that these mutations can present with less complex phenotypes, like hereditary spastic paraplegia (HSP) or spastic ataxia. Thus, PNPLA6 mutations cause a range of neurodegenerative diseases, including two recognized syndromes.
Structure and Biosynthesis of the Murein (Peptidoglycan) Sacculus
2014-04-08

This chapter reviews the murein structure and biosynthesis and the possible mechanism(s) of enlargement during growth of gram-negative bacteria. Unless otherwise stated, the presented data were obtained in studies with Escherichia coli, which is the most extensively studied gram-negative bacterium with respect to murein structure and biosynthesis. The major subunits in the murein of E. coli are the disaccharide tetrapeptide monomer and the DD-cross-linked bisdisaccharide tetratetrapeptide dimer. The layered murein cannot be perfect for two reasons. First, compared with the dimensions of the cell, the glycan strands are rather short. Second, the percentage of cross-linked peptides is slightly lower than the theoretical value of 50%. The final steps in murein synthesis take place at the periplasmic side of the cytoplasmic membrane and involve two reactions. First, the murein glycan strands are oligomerized by transglycosylation, and second, the peptide cross-links are formed by transpeptidation. Of the six known lytic transglycosylases of E. coli, only one is soluble (Slt70), whereas five are lipoproteins anchored to the outer membrane (MltA, MltB, MltC, MltD, and EmtA) and face into the periplasm. Murein hydrolases are enzymes that cleave covalent bonds in the murein sacculus or in murein fragments. Morphogenesis of E. coli seems rather simple with two phases in the cell cycle. Most models have in common that the enlargement of the sacculus is achieved by the insertion of new glycan strands and that both synthesis of new murein and hydrolysis of bonds within the existing sacculus are combined.
Transfer of Energy and Information across the Periplasm in Iron Transport and Regulation
2014-04-08

Two periplasmic functions are discussed in this chapter: (i) the transfer of energy from the cytoplasmic membrane across the periplasm to the outer membrane, and (ii) the transfer of information from the outer membrane across the periplasm through the cytoplasmic membrane into the cytoplasm. To enter gram-negative bacteria, substrates must cross three compartments: the outer membrane, the periplasm, and the cytoplasmic membrane. Most substrates diffuse through outer membrane porins into the periplasm and then are actively transported, i.e., with energy coupling, across the cytoplasmic membrane. Early studies have demonstrated that TonB is involved in iron transport and that the proton motive force serves as energy source for TonB-dependent processes. It is currently impossible to decide whether the various results reflect different TonB states during the reaction cycle–energization, deenergization, interaction with ExbB and ExbD within the cytoplasmic membrane and the periplasm, and binding to and release from transporters–or whether some results are experimental artifacts caused in vitro by the use of truncated forms that lack the N-terminal membrane anchor, which is essential for TonB activity. The periplasm–once considered not more than a space between the outer membrane and the cytoplasmic membrane–is now known to be a compartment through which energy and information flow. Understanding of the underlying mechanisms will require much sophisticated work since the three compartments cannot be taken apart without loss of essential aspects of periplasmic functions.
Long-Term Safety and Maintenance of Efficacy From an Open-Label Extension of the Double-Blind Pivotal Study of Levodopa-Carbidopa Intestinal Gel (LCIG) in Advanced Parkinson’s Disease Patients (P7.081)
2014-04-08

OBJECTIVE: To examine the long-term safety and maintenance of efficacy of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced Parkinson's disease (PD) who received open-label LCIG treatment after completing a 12-week double-blind, double-dummy trial in which they were randomized to either LCIG or LC-Oral. BACKGROUND: Fluctuating plasma levodopa levels are associated with motor complications. LCIG is delivered continuously via an intrajejunal percutaneous gastrostomy tube. DESIGN/METHODS: Prior to the 52-week open-label extension, patients were retitrated to establish the optimum LCIG dose. For efficacy analyses, patients were grouped by whether they had received LCIG or LC-Oral in the previous double-blind trial (continuing-LCIG vs. LCIG-naïve patients); the change from baseline was evaluated. RESULTS: LCIG-naïve patients (N=29) showed improvement in "Off" time (mean [SD] change from baseline to endpoint = -2.3[2.8], P<0.001) and "On" time without troublesome dyskinesia (change from baseline to endpoint = 2.2[3.7], P=0.005) starting at week 4. Continuing-LCIG patients (N=33) showed maintenance of effect ("Off" time change from baseline to endpoint = -0.4[2.7], P=0.377) or further improvement ("On" time without troublesome dyskinesia change from baseline to endpoint = 1.0[2.6], P=0.036). PDQ-39 scores improved in LCIG-naïve patients as early as 12 weeks (change from baseline at week 12 = -5.5[10.8], P=0.018, change at endpoint = -3.5[13.4], P=0.191), while sustained improvement was noted among continuing-LCIG patients (change from baseline to endpoint = 1.5[12.7], P=0.505). Most subjects (95%) reported 蠅1 adverse event, yet only 3 subjects (4.8%) discontinued due to an adverse event. The most common AEs reported were incision site erythema (29%), fall (21%), vitamin B6 decreased (21%), and postoperative wound infection (18%). CONCLUSIONS: Continuing-LCIG patients continued to derive benefit from LCIG without developing tolerance while the magnitude of benefit among LCIG-naïve patients was similar to that observed in the pivotal study (Olanow, MDS, 2012). AE profile was similar to that observed in other phase 3 studies (Fernandez, Parkinsonism & Related Disorders, 2013). Study Supported by: AbbVie