julilili42/papers huggingface dataset:
Role of Loc1p in assembly and reorganization of nuclear ASH1 messenger ribonucleoprotein particles in yeast
2013-12-09

Significance Cytoplasmic mRNA localization is preceded by the formation of nuclear pre-mRNPs. To date the requirement of the nuclear mRNP assembly is not well understood. We used ASH1 mRNA localization from budding yeast to understand the mechanisms of nuclear priming for cytoplasmic mRNA transport. We found that the nuclear factor Loc1p is required to stably and specifically tether the bona fide ASH1 RNA-binding protein She2p to RNA in the nucleus, offering an explanation for the requirement of Loc1p for ASH1 mRNA localization. Because Loc1p is not part of the cytoplasmic ASH1 mRNP, it must be removed before mRNA transport. We show that the cytoplasmic transport factor She3p displaces Loc1p from the ASH1 mRNP, allowing for the maturation of the localizing ASH1 mRNP.
What happens to deformed rocks after deformation? A refined model for recovery based on numerical simulations
2013-12-09

Abstract Deformation, in large parts of the middle crust, results in strained rocks consisting of grains with variable dislocation densities and microstructures which are characterized by gradual distortion and subgrain structures. Post-deformation residence of these rocks at elevated temperatures results in microstructural adjustments through static recovery and recrystallization. Here, we employ a numerical technique to simulate intragrain recovery at temperatures at or below the deformation temperature. The simulation is based on minimization of the stored energy, related to misorientation through local rotation of physical material points relative to their immediate environment. Three temperature- and/or deformation-geometry-dependent parameters were systematically varied: (1) deformation-induced dislocation types, (2) dislocation mobility and (3) size of dislocation interaction volume. Comparison with previously published in situ experiments shows consistency of numerical and experimental results. They show temperature- and dislocation-type-dependent small-scale fluctuations in subgrain-boundary misorientations and orientation variation within subgrains. These can be explained by the combined effect of increase in dislocation interaction volume and activation of climb. Our work shows microstructure can be significantly modified even if the post-deformational temperature is at or below the deformation temperature: a scenario relevant for most deformed rocks.
A New In Vitro Model to Study Cellular Responses after Thermomechanical Damage in Monolayer Cultures
2013-12-09

Although electrosurgical instruments are widely used in surgery to cut tissue layers or to achieve hemostasis by coagulation (electrocautery), only little information is available concerning the inflammatory or immune response towards the debris generated. Given the elevated local temperatures required for successful electrocautery, the remaining debris is likely to contain a plethora of compounds entirely novel to the intracorporal setting. A very common in vitro method to study cell migration after mechanical damage is the scratch assay, however, there is no established model for thermomechanical damage to characterise cellular reactions. In this study, we established a new in vitro model to investigate exposure to high temperature in a carefully controlled cell culture system. Heatable thermostat-controlled aluminium stamps were developed to induce local damage in primary human umbilical vein endothelial cells (HUVEC). The thermomechanical damage invoked is reproducibly locally confined, therefore allowing studies, under the same experimental conditions, of cells affected to various degrees as well as of unaffected cells. We show that the unaffected cells surrounding the thermomechanical damage zone are able to migrate into the damaged area, resulting in a complete closure of the 'wound' within 48 h. Initial studies have shown that there are significant morphological and biological differences in endothelial cells after thermomechanical damage compared to the mechanical damage inflicted by using the unheated stamp as a control. Accordingly, after thermomechanical damage, cell death as well as cell protection programs were activated. Mononuclear cells adhered in the area adjacent to thermomechanical damage, but not to the zone of mechanical damage. Therefore, our model can help to understand the differences in wound healing during the early phase of regeneration after thermomechanical vs. mechanical damage. Furthermore, this model lends itself to study the response of other cells, thus broadening the range of thermal injuries that can be analysed.
Sleep enhances inhibitory behavioral control in discrimination learning in rats
2013-12-09

Sleep supports the consolidation of memory, and it has been proposed that this enhancing effect of sleep pertains in particular to memories which are encoded under control of prefrontal-hippocampal circuitry into an episodic memory system. Furthermore, repeated reactivation and transformation of such memories during sleep are thought to promote the de-contextualization of these memories. Here, we aimed to establish a behavioral model for the study of such sleep-dependent system consolidation in rats, using a go/nogo conditional discrimination learning task known to essentially depend on prefrontal-hippocampal function. Different groups of rats were trained to criterion on this task and, then, subjected to 80-min retention intervals filled with spontaneous morning sleep, sleep deprivation, or spontaneous evening wakefulness. In a subsequent test phase, the speed of relearning of the discrimination task was examined as indicator of memory, whereby rats were either tested in the same context as during training or in a different context. Sleep promoted relearning of the conditional discrimination task, and this effect was similar for testing memory in the same or different context (p < 0.001). Independent of sleep and wakefulness during the retention interval, animals showed faster relearning when tested in the same context as during learning, compared with testing in a different context (p < 0.001). The benefitting effect of sleep on discrimination learning was primarily due to an enhancing effect on response suppression during the nogo stimulus. We infer from these results that sleep enhances memory for inhibitory behavioral control in a generalized context-independent manner and thereby might eventually also contribute to the abstraction of schema-like representations.
Heavy Group 15 Element Compounds of a Sterically Demanding Bis(iminophosphorane)methanide and -methanediide
2013-12-09

Complexes of the heavy pnictogen elements Sb and Bi of monoanionic (C,N-chelated: Sb, Bi) and dianionic (N,C,N-pincer type: Bi) bulky substituted bis(diphenyl(arylimino)phosphorano)methane H2C(Ph2PNR)2 (R = 2,6-diisopropylphenyl (dipp)) have been prepared via metathetical reactions, and tautomerism within the monoanionic ligand backbone has been observed. The complexes have been characterized by means of X-ray analysis and NMR studies. The dianionic complex was found to feature the rare structural motif of a formal carbon–bismuth(III) double bond. The molecular structure of the solvate-free potassium salt K[HC(Ph2PNdipp)2] is reported.
Trimeric Cage Complexes of Platinum Group and Coin Metals
2013-12-09

Abstract The treatment of cis , cis ‐1,3,5‐tris(diphenylphosphinomethyl)cyclohexane (tdppmcy) with Rh(CO)Cl(PPh 3 ) 2 , MCl 2 L 2 (M = Pd, Pt; L = PhCN, MeCN), Pt(CN) 2 , AgBF 4 , or Au(Cl)PPh 3 in a stoichiometric ratio of 2:3 affords the trimeric macrocyclic cage compounds [M] 3 (tdppmcy) 2 {[M] = trans ‐Rh(CO)Cl ( 2 ), trans ‐PdCl 2 ( 3 ), trans ‐Pt(CN) 2 ( 4b ), Ag + ( 5 ), and AuCl ( 6 )} in good yields. Only when PtCl 2 (PhCN) 2 was used as complex precursor, the formation of coordination polymers was observed. NMR spectroscopy in solution as well as single‐crystal X‐ray diffraction analyses demonstrate that in all cases two tdppmcy ligands coordinate three metal fragments exclusively in trans fashion.
Stable numerosity representations irrespective of magnitude context in macaque prefrontal cortex
2013-12-09

Abstract Cognitively demanding tasks require neurons of the prefrontal cortex ( PFC ) to encode divergent behaviorally relevant information. In discrimination tasks with arbitrary and learned categories, context‐specific parameters shape and adapt the tuning functions of PFC neurons. We explored if and how selectivity of PFC neurons to visual numerosities, a ‘natural’ abstract category, may change depending on the magnitude context. Two monkeys discriminated visual numerosities (varying numbers of dot items) in a delayed match‐to‐sample ( DMS ) task while single‐cell activity was recorded from the lateral PFC . During a given recording session, the numerosity task was either presented in isolation or randomly intermixed with DMS tasks with line lengths and colors as discriminative stimuli. We found that the context of numerosity discriminations did not influence the response properties of numerosity detectors. The numerosity tuning curves of selective neurons, i.e. the preferred numerosity and the sharpness of tuning, remained stable, irrespective of whether the numerosity task was presented in a pure numerosity block or a mixed magnitude block. Our data suggest that numerosity detectors in the PFC do not adapt their response properties to code stimuli according to changing magnitude context. Rather, numerosity representations seem to rely on a sparse and stable ‘labeled line’ code. In contrast to arbitrarily learned categories, numerosity as a ‘natural’ category may possess a privileged position and their neuronal representations could thus remain unaffected by magnitude context.
Myeloid-Derived Suppressor Cells Predict Survival of Patients with Advanced Melanoma: Comparison with Regulatory T Cells and NY-ESO-1- or Melan-A–Specific T Cells
2013-12-10

Abstract Purpose: To analyze the prognostic relevance and relative impact of circulating myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) compared with functional tumor antigen–specific T cells in patients with melanoma with distant metastasis. Experimental Design: The percentage of CD14+CD11b+HLA-DR−/low MDSCs, CD4+CD25+FoxP3+ Tregs, and the presence of NY-ESO-1- or Melan-A–specific T cells was analyzed in 94 patients and validated in an additional cohort of 39 patients by flow cytometry. Univariate survival differences were calculated according to Kaplan–Meier and log-rank tests. Multivariate analyses were performed using Cox regression models. Results: NY-ESO-1–specific T cells, the M-category, and the frequency of MDSCs were associated with survival. The absence of NY-ESO-1–specific T cells and the M-category M1c independently increased the risk of death. In a second Cox model not considering results on antigen-specific T cells, a frequency of &amp;gt;11% MDSCs showed independent impact. Its association with survival was confirmed in the additional patient cohort. Median survival of patients with a lower frequency of MDSCs was 13 months versus 8 months for others (P &amp;lt; 0.001, combined cohorts). We observed a strong correlation between high levels of MDSCs and the absence of melanoma antigen–specific T cells implying a causal and clinically relevant interaction. No prognostic impact was observed for Tregs. Conclusions: Circulating CD14+CD11b+HLA-DR−/low MDSCs have a negative impact on survival and inversely correlate with the presence of functional antigen–specific T cells in patients with advanced melanoma. Our findings provide a rationale to investigate MDSC-depleting strategies in the therapeutic setting especially in combination with vaccination or T-cell transfer approaches. Clin Cancer Res; 20(6); 1601–9. ©2013 AACR.
Quark sector of the QCD groundstate in Coulomb gauge
2013-12-10

The variational approach to Yang-Mills theory in Coulomb gauge is extended to\\nfull QCD. For the quark sector we use a trial wave functional, which goes\\nbeyond the previously used BCS-type state and which explicitly contains the\\ncoupling of the quarks to transverse gluons. This quark wave functional\\ncontains two variational kernels: One is related to the quark condensate and\\noccurs already in the BCS-type states. The other represents the form factor of\\nthe coupling of the quarks to the transverse gluons. Minimization of the energy\\ndensity with respect to these kernels results in two coupled integral (gap)\\nequations. These equations are solved numerically using the confining part of\\nthe non-Abelian color Coulomb potential and the lattice static gluon propagator\\nas input. With the additional coupling of quarks to transverse gluons included\\nthe low energy chiral properties increase substantially towards their\\nphenomenological values. We obtain a reasonable description of the chiral\\ncondensate, which for a vanishing current quark mass is obtained in the range\\nof 190-235 MeV. The coupling of the quarks to the transverse gluons enhances\\nthe constituent quark mass by about 60% in comparison to the pure BCS ansatz.\\n
Neuron-Specific Mitochondrial DNA Deletion Levels in Sporadic Alzheimer´s Disease
2013-12-10

Oxidative stress is implicated in the pathogenesis of neurodegenerative diseases, including sporadic Alzheimer ́s disease (AD). Mitochondrial DNA (mtDNA) deletions are markers of oxidative damage and increase with age. To unravel the impact of mtDNA damage on AD development, we analyzed mtDNA deletion levels in diverse neuronal cell types of four brain regions (hippocampal CA1 and CA2 regions, nucleus tractus spinalis nervi trigemini, and the cerebellum) that exhibit differing levels of vulnerability to AD related changes at progressive Braak stages compared with age-matched controls. Neurons from these four brain regions were collected using laser microdissection, and analyzed using quantitative polymerase chain reaction (qPCR). Although, no correlation between mtDNA deletion levels and AD progression were found, the data revealed regional and cell type specific selective vulnerability towards mtDNA deletion levels. In conclusion, unexpected results were obtained as granule cells from the cerebellum and neurons from the nucleus tractus spinalis nervi trigemini of the brain stem displayed significant higher mtDNA deletion levels than pyramidal cells from hippocampal CA1 and CA2 region in age and AD.
DLOGTIME Proof Systems
2013-12-10

We define DLOGTIME proof systems, DLTPS, which generalize NC0 proof systems. It is known that functions such as Exact_k and Majority do not have NC0 proof systems. Here, we give a DLTPS for Exact_k (and therefore for Majority) and also for other natural functions such as Reach and Cliquek. Though many interesting functions have DLTPS, we show that there are languages in NP which do not have DLTPS. We consider the closure properties of DLTPS and prove that they are closed under union and concatenation but are not closed under intersection and complement. Finally, we consider a hierarchy of polylogarithmic time proof systems and show that the hierarchy is strict.
Dominant spinal muscular atrophy due to BICD2: a novel mutation refines the phenotype
2013-12-11

Spinal muscular atrophies (SMA) are a genetically and clinically heterogeneous group of disorders predominantly of the anterior horn. While the large majority of recessive SMA cases can be explained by mutations in SMN1 , the genetic basis of dominant SMA has remained largely elusive. Although mutations have been identified in >12 genes, mutations are found only in less than 30% of dominant SMA cases.1 Recently, BICD2 has been identified to cause dominant SMA.1–3 Here, we provide additional evidence that BICD2 is a cause of dominant SMA and report detailed clinical, electrophysiological and MRI data from a three-generation family with cosegregation of a novel BICD2 mutation. These findings extend current notions of BICD2 , demonstrating that it can present with adult-onset combined proximal and distal lower extremity SMA. Our clinical observations not only extend the phenotype of BICD2 -related disease, but might also provide novel insights in the pathophysiology of the disease. The 44-year-old German female index patient (III-2, figure 1A) presented with a 3-year history of a mild symmetric proximal (Medical Research Council (MRC) grade 4) and distal (MRC grade 3) paresis of lower extremities. While able to ambulate independently, she was unable to walk on heels and had difficulties walking on toes and climbing >10 stairs. There was areflexia of lower limbs, high-arched feet (figure 1C) and complete atrophy of the quadriceps muscle (figure 1D) without genu recurvatum. She recalled minor problems in jumping during sports at school, however had not sought medical advice so far. ...
The effect of caffeine on spontaneous pupillary oscillations
2013-12-11

Abstract Purpose Caffeine stimulates the central nervous system, but the duration and extent of its influence on the pupil are not known. The aim of this study was to determine whether caffeine could have an effect on pupillary sleepiness waves, measured with the Pupillographic Sleepiness Test ( PST ) during routine clinical PST testing, where the caffeine dose‐response of a participant cannot be registered before recording. Methods Twenty participants (aged between 22 and 51 years, (mean 30.9 years ±8.9 SD , 11 women and nine men),.were tested at seven different time‐points over 4.5 h. Each participant was tested under four conditions with coffee drunk or not between 1 and 2 h before the first measurement and/or 15 min afterwards. Results Caffeine caused a reduction in the Pupillary Unrest Index ( PUI ) with a maximal effect 1.25 h after consumption. A prolonged effect is found if coffee was consumed between 1 and 2 h before the first measurement. More excessive coffee consumers show prolongation of the effect. Subjective scales of sleepiness, alertness and craving for caffeine were significantly correlated to linear logarithm of PUI (ln PUI ). Conclusions We conclude that caffeine causes a dampening of the pupillary oscillations in well‐rested participants. As caffeine consumption can affect the PST for up to 6.5 h after intake, it is recommended that if PST measurements are to be carried out in the morning, caffeine consumption should not be allowed after midnight.
Prevalence and Prognostic Value of Disseminated Tumor Cells in Primary Endometrial, Cervical and Vulvar Cancer Patients
2013-12-11

Tumor cell dissemination is common in gynecological cancer. In contrast to breast cancer, DTCs that derive from cervical, endometrial or vulvar cancer have less potential to initiate metastatic regrow. The molecular mechanisms underlying this observation warrant further investigation.
Stepwise Solid‐Phase Synthesis and Solid‐State Electrochemistry of Redox‐Active Viologen Core/Shell‐Structured Modified Silica Materials
2013-12-11

Abstract Core/shell‐structured viologen‐modified Stöber silica particles with diameters of approximately 235 nm are prepared in a stepwise, solid‐phase synthesis. The nonporous and spherical silica base particles are obtained through a sol–gel process from tetraethoxysilane followed by a post‐synthetic calcination step and characterized by means of scanning electron microscopy, nitrogen adsorption/desorption experiments, diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, Gay‐Lussac pycnometry in water, and dynamic light scattering. Coating with triethoxysilane yields SiH‐terminated particles, which are further reacted with the linker, 11‐bromo‐1‐undecene, in a thermally induced hydrosilylation. The resulting kinetically inert and thermodynamically stable SiC bond ensures strong attachment to the silica surface. The viologen units are generated by alkylation with 1‐methyl[4,4′]bipyridinium iodide directly on the particle surface. The successful attachment is confirmed by diffuse reflectance UV/Vis, DRIFT, and 13 C cross‐polarization/magic‐angle spinning nuclear magnetic resonance spectroscopy. The viologen shell of the particles is electrochemically addressable. In cyclic voltammetry experiments, under three‐phase junction conditions with modified gold and paraffin‐impregnated graphite electrodes, the immobilized viologen units are reduced to the neutral state in two consecutive electron‐transfer reactions via a mono radical cation species. The in situ electrolysis of suspended particles leads to a material with a diamagnetic core (silica) and a paramagnetic shell (viologen mono radical cations). Electron paramagnetic resonance experiments demonstrate that the radical cations are strongly attached to the particle surface. The material and electrochemical properties of the particles are compared to amorphous silica and to a viologen‐modified Stöber material based on a well‐established immobilization strategy (condensation of alkoxysilane to surface silanol groups).
Quasi-periodic oscillations in superfluid magnetars
2013-12-12

We study the time-evolution of axisymmetric oscillations of superfluid\\nmagnetars with a poloidal magnetic field and an elastic crust, working in\\nNewtonian gravity. Extending earlier models, we study the effects of\\ncomposition gradients and entrainment on the magneto-elastic wave spectrum and\\non the potential identification of the observed quasi periodic oscillations\\n(QPOs). We use two-fluid polytropic equations of state to construct our stellar\\nmodels, which mimic realistic composition gradient configurations. The basic\\nfeatures of the axial axisymmetric spectrum of normal fluid stars are\\nreproduced by our results and in addition we find several magneto-elastic waves\\nwith a mixed character. In the core, these oscillations mimic the shear mode\\npattern of the crust as a result of the strong dynamical coupling between these\\ntwo regions. Incorporating the most recent entrainment configurations in our\\nmodels, we find that they have a double effect on the spectrum: the magnetic\\noscillations of the core have a frequency enhancement, while the mixed\\nmagneto-elastic waves originating in the crust are moved towards the\\nfrequencies of the single-fluid case. The distribution of lower-frequency\\nmagneto-elastic oscillations for our models is qualitatively similar to the\\nobserved magnetar QPOs with Hz. \\\\emph{In particular, some of these\\nQPOs could represent mixed magneto-elastic oscillations with frequencies not\\ngreatly different from the crustal modes of an unmagnetised star.} We find that\\nmany QPOs could even be accounted for using a model with a relatively weak\\npolar field of G, because of the superfluid\\nenhancement of magnetic oscillations. Finally, we discuss the possible\\nidentification of 625 and 1837~Hz QPOs either with non-axisymmetric modes or\\nwith high-frequency axisymmetric QPOs excited by crustal mode overtones.\\n