julilili42/papers huggingface dataset:
Antileukemia T-cell responses in CLL – We don't need no aberration
2015-03-16

Effective antigen-specific cancer immunotherapy requires exact knowledge of tumor-associated epitopes that can act as rejection antigens. Although the current paradigm views mutation-derived neoantigens as the most promising targets, we have recently demonstrated that leukemia-specific T-cell responses associated with survival benefit in CLL patients target a panel of non-mutated tumor-associated antigens.
Reactivity of Yttrium Methyl Complexes: Hydrido Transfer Capability of Selected Alkylalanes
2015-03-16

The reactivity of alkylaluminum hydrides HAlMe2, HAl(CH2SiMe3)2, and H2AlMes* (Mes* = C6H2tBu3-2,4,6) toward yttrium methyl complexes was assessed. From the reaction with [Cp2YMe]2 the corresponding methylated alkylaluminum compounds could be isolated and characterized along with [Cp2Y(thf)(μ-H)]2, obtained upon workup in thf (Cp = C5H5 = cyclopentadienyl). Structurally characterized complexes Cp14Y6H3Cl and Cp15Y6H3 represent side-products of the transformation. The reactions of [YMe3]n and [(C5Me5)YMe2]3 indicated occurrence of hydrido transfer for H2AlMes* and led to product mixtures for HAl(CH2SiMe3)2. Following the reaction of HAlMe2 with these compounds as well as the half-sandwich derivatives (C5Me4R)Y(AlMe4)2 (R = Me, SiMe3) indicated reversible hydrido binding, leading ultimately to the formation of insoluble hydride clusters. The organoaluminum compounds [HAl(CH2SiMe3)2]3, [(μ-H)(Me)AlMes*]2, and Me2AlMes* were analyzed by X-ray crystallography.
Targeted epigenome editing of an endogenous locus with chromatin modifiers is not stably maintained
2015-03-17

Background: DNA methylation and histone 3 lysine 9 (H3K9) methylation are considered as epigenetic marks that can be inherited through cell divisions. To explore the functional consequences and stability of these modifications, we employed targeted installment of DNA methylation and H3K9 methylation in the vascular endothelial growth factor A (VEGF-A) promoter using catalytic domains of DNA or H3K9 methyltransferases that are fused to a zinc finger protein which binds a site in the VEGF-A promoter. Results: Expression of the targeted DNA and H3K9 methyltransferases caused dense deposition of DNA methylation or H3K9 di- and trimethylation in the promoter of VEGF-A and downregulation of VEGF-A gene expression. We did not observe positive feedback between DNA methylation and H3K9 methylation. Upon loss of the targeted methyltransferases from the cells, the epigenetic marks, chromatin environment, and gene expression Levels returned to their original state, indicating that both methylation marks were not stably propagated after their installment. Conclusions: The clear anti-correlation between DNA or H3K9 methylation and gene expression suggests a direct role of these marks in transcriptional control. The lack of maintenance of the transiently induced silenced chromatin state suggests that the stability of epigenetic signaling is based on an epigenetic network consisting of several molecular marks. Therefore, for stable reprogramming, either multivalent deposition of functionally related epigenetic marks or longer-lasting trigger stimuli might be necessary.
Methodological aspects to be considered when measuring the approximate number system (ANS) â€“ a research review
2015-03-17

According to a dominant view, the approximate number system (ANS) is the foundation of symbolic math abilities. Due to the importance of math abilities for education and career, a lot of research focuses on the investigation of the ANS and its relationship with math performance. However, the results are inconsistent. This might be caused by studies differing greatly regarding the operationalization of the ANS (i.e., tasks, dependent variables). Moreover, many methodological aspects vary from one study to the next. In the present review, we discuss commonly used ANS tasks and dependent variables regarding their theoretical foundation and psychometric features. We argue that the inconsistent findings concerning the relationship between ANS acuity and math performance may be partially explained by differences in reliability. Furthermore, this review summarizes methodological aspects of ANS tasks having important impacts on the results, including stimulus range, visual controls, presentation duration of the stimuli and feedback. Based on this review, we give methodological recommendations on how to assess the ANS most reliably and most validly. All important methodological aspects to be considered when designing an ANS task or comparing results of different studies are summarized in two practical checklists.
Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals
2015-03-17

Polymorphisms rs6232 and rs6234/rs6235 in PCSK1 have been associated with extreme obesity [e.g. body mass index (BMI) ≥ 40 kg/m(2)], but their contribution to common obesity (BMI ≥ 30 kg/m(2)) and BMI variation in a multi-ethnic context is unclear. To fill this gap, we collected phenotypic and genetic data in up to 331 175 individuals from diverse ethnic groups. This process involved a systematic review of the literature in PubMed, Web of Science, Embase and the NIH GWAS catalog complemented by data extraction from pre-existing GWAS or custom-arrays in consortia and single studies. We employed recently developed global meta-analytic random-effects methods to calculate summary odds ratios (OR) and 95% confidence intervals (CIs) or beta estimates and standard errors (SE) for the obesity status and BMI analyses, respectively. Significant associations were found with binary obesity status for rs6232 (OR = 1.15, 95% CI 1.06-1.24, P = 6.08 × 10(-6)) and rs6234/rs6235 (OR = 1.07, 95% CI 1.04-1.10, P = 3.00 × 10(-7)). Similarly, significant associations were found with continuous BMI for rs6232 (β = 0.03, 95% CI 0.00-0.07; P = 0.047) and rs6234/rs6235 (β = 0.02, 95% CI 0.00-0.03; P = 5.57 × 10(-4)). Ethnicity, age and study ascertainment significantly modulated the association of PCSK1 polymorphisms with obesity. In summary, we demonstrate evidence that common gene variation in PCSK1 contributes to BMI variation and susceptibility to common obesity in the largest known meta-analysis published to date in genetic epidemiology.
Electronic heat current rectification in hybrid superconducting devices
2015-03-17

In this work, we review and expand recent theoretical proposals for the realization of electronic thermal diodes based on tunnel-junctions of normal metal and superconducting thin films. Starting from the basic rectifying properties of a single hybrid tunnel junction, we will show how the rectification efficiency can be largely increased by combining multiple junctions in an asymmetric chain of tunnel-coupled islands. We propose three different designs, analyzing their performance and their potential advantages. Besides being relevant from a fundamental physics point of view, this kind of devices might find important technological application as fundamental building blocks in solid-state thermal nanocircuits and in general-purpose cryogenic electronic applications requiring energy management.
Mutations in CIZ1 are not a major cause for dystonia in Germany
2015-03-17

Additional Supporting Information may be found in the online version of this article. Supplementary Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Intercellular Diffusion of a Fluorescent Sucrose Analog via the Septal Junctions in a Filamentous Cyanobacterium
2015-03-18

ABSTRACT Many filamentous cyanobacteria produce specialized nitrogen-fixing cells called heterocysts, which are located at semiregular intervals along the filament with about 10 to 20 photosynthetic vegetative cells in between. Nitrogen fixation in these complex multicellular bacteria depends on metabolite exchange between the two cell types, with the heterocysts supplying combined-nitrogen compounds but dependent on the vegetative cells for photosynthetically produced carbon compounds. Here, we used a fluorescent tracer to probe intercellular metabolite exchange in the filamentous heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120. We show that esculin, a fluorescent sucrose analog, is incorporated by a sucrose import system into the cytoplasm of Anabaena cells. The cytoplasmic esculin is rapidly and reversibly exchanged across vegetative-vegetative and vegetative-heterocyst cell junctions. Our measurements reveal the kinetics of esculin exchange and also show that intercellular metabolic communication is lost in a significant fraction of older heterocysts. SepJ, FraC, and FraD are proteins located at the intercellular septa and are suggested to form structures analogous to gap junctions. We show that a Δ sepJ Δ fraC Δ fraD triple mutant shows an altered septum structure with thinner septa but a denser peptidoglycan layer. Intercellular diffusion of esculin and fluorescein derivatives is impaired in this mutant, which also shows a greatly reduced frequency of nanopores in the intercellular septal cross walls. These findings suggest that FraC, FraD, and SepJ are important for the formation of junctional structures that constitute the major pathway for feeding heterocysts with sucrose. IMPORTANCE Anabaena and its relatives are filamentous cyanobacteria that exhibit a sophisticated form of prokaryotic multicellularity, with the formation of differentiated cell types, including normal photosynthetic cells and specialized nitrogen-fixing cells called heterocysts. The question of how heterocysts communicate and exchange metabolites with other cells in the filament is key to understanding this form of bacterial multicellularity. Here we provide the first information on the intercellular exchange of a physiologically important molecule, sucrose. We show that a fluorescent sucrose analog can be imported into the Anabaena cytoplasm by a sucrose import system. Once in the cytoplasm, it is rapidly and reversibly exchanged among all of the cells in the filament by diffusion across the septal junctions. Photosynthetically produced sucrose likely follows the same route from cytoplasm to cytoplasm. We identify some of the septal proteins involved in sucrose exchange, and our results indicate that these proteins form structures functionally analogous to metazoan gap junctions.
In vitroelastogenesis: instructing human vascular smooth muscle cells to generate an elastic fiber-containing extracellular matrix scaffold
2015-03-18

Elastic fibers are essential for the proper function of organs including cardiovascular tissues such as heart valves and blood vessels. Although (tropo)elastin production in a tissue-engineered construct has previously been described, the assembly to functional elastic fibers in vitro using human cells has been highly challenging. In the present study, we seeded primary isolated human vascular smooth muscle cells (VSMCs) onto 3D electrospun scaffolds and exposed them to defined laminar shear stress using a customized bioreactor system. Increased elastin expression followed by elastin deposition onto the electrospun scaffolds, as well as on newly formed fibers, was observed after six days. Most interestingly, we identified the successful deposition of elastogenesis-associated proteins, including fibrillin-1 and -2, fibulin-4 and -5, fibronectin, elastin microfibril interface located protein 1 (EMILIN-1) and lysyl oxidase (LOX) within our engineered constructs. Ultrastructural analyses revealed a developing extracellular matrix (ECM) similar to native human fetal tissue, which is composed of collagens, microfibrils and elastin. To conclude, the combination of a novel dynamic flow bioreactor and an electrospun hybrid polymer scaffold allowed the production and assembly of an elastic fiber-containing ECM.
Prognostic relevance of positive urine markers in patients with negative cystoscopy during surveillance of bladder cancer
2015-03-18

Patients with positive urine markers at time of negative cystoscopy are at increased risk of recurrence and progression. In patients with negative cytology, only NMP22 is predictive for recurrence. Patients with negative marker combinations including NMP22 harbour a low risk of recurrence. Therefore, the endoscopic follow-up regimen may be attenuated in this group of patients.
CT Evaluation of Small-Diameter Coronary Artery Stents: Effect of an Integrated Circuit Detector with Iterative Reconstruction
2015-03-18

The implementation of an integrated-circuit CT detector provides substantially sharper out-of-plane resolution of coronary artery stents at 0.5-mm section thickness, while the use of iterative image reconstruction mostly improves in-plane stent visualization.
Financial Frictions and Foreign Direct Investment: Theory and Evidence from Japanese Microdata
2015-03-18

We use Japanese microdata to examine how financial market frictions affect foreign direct investment (FDI). The Japanese land price bubble and banking trouble in the late 1980s and early 1990s serve as a quasi natural experiment to identify two possible transmission channels from financial shocks to FDI: (i) a collateral channel, whereby changes in the value of collateral affect investors’ ability to borrow; and (ii) a lending channel, whereby changes in bank health affect banks’ ability to lend. We find evidence that both transmission channels are statistically significant and economically important.
Competition format, championship uncertainty and stadium attendance in European football – a small league perspective
2015-03-19

To increase the number of regular season games, small football leagues are often organized as quadruple round robin tournaments with teams playing each other four times. Theoretically , however, the more games played, the less uncertain is the championship race, reducing fan interest in the league. This article uses data from Austria and Switzerland to study the relationship between competition format, championship uncertainty and attendance demand empirically . Results suggest that a team still in contention to win the championship positively affects attendance, while it is not the specificity of the competition format that per se contributes to less championship uncertainty.
Cell Therapy for Stress Urinary Incontinence
2015-03-19

Urinary incontinence (UI) is the involuntary loss of urine and is a common condition in middle-aged and elderly women and men. Stress urinary incontinence (SUI) is caused by leakage of urine when coughing, sneezing, laughing, lifting, and exercise, even standing leads to increased intra-abdominal pressure. Other types of UI also exist such as urge incontinence (also called overactive bladder), which is a strong and unexpected sudden urge to urinate, mixed forms of UI that result in symptoms of both urge and stress incontinence, and functional incontinence caused by reduced mobility, cognitive impairment, or neuromuscular limitations that impair mobility or dexterity. However, for many SUI patients, there is significant loss of urethral sphincter muscle due to degeneration of tissue, the strain and trauma of pregnancy and childbirth, or injury acquired during surgery. Hence, for individuals with SUI, a cell-based therapeutic approach to regenerate the sphincter muscle offers the advantage of treating the cause rather than the symptoms. We discuss current clinically relevant cell therapy approaches for regeneration of the external urethral sphincter (striated muscle), internal urethral sphincter (smooth muscle), the neuromuscular synapse, and blood supply. The use of mesenchymal stromal/stem cells is a major step in the right direction, but they may not be enough for regeneration of all components of the urethral sphincter. Inclusion of other cell types or biomaterials may also be necessary to enhance integration and survival of the transplanted cells.
Discovery of variable VHEγ-ray emission from the binary system 1FGL J1018.6–5856
2015-03-19

Re-observations with the H.E.S.S. telescope array of the very-high-energy (VHE) source HESS J1018-589 A coincident with the Fermi-LAT -ray binary 1FGL J1018.6-5856 have resulted in a source detection significance of more than 9 , and the detection of variability ( / of 238.3/155) in the emitted -ray flux. This variability confirms the association of HESS J1018-589 A with the high-energy -ray binary detected by Fermi-LAT, and also confirms the point-like source as a new very-high-energy binary system. The spectrum of HESS J1018-589 A is best fit with a power-law function with photon index . Emission is detected up to ~20 TeV. The mean differential flux level is TeV cm s at 1 TeV, equivalent to ~1% of the flux from the Crab Nebula at the same energy. Variability is clearly detected in the night-by-night lightcurve. When folded on the orbital period of 16.58 days, the rebinned lightcurve peaks in phase with the observed X-ray and high-energy phaseograms. The fit of the H.E.S.S. phaseogram to a constant flux provides evidence of periodicity at the level of 3 . The shape of the VHE phaseogram and measured spectrum suggest a low inclination, low eccentricity system with a modest impact from VHE -ray absorption due to pair production ( &lt; 1 at 300 GeV).
Melanoma brain metastasis is independent of lactate dehydrogenase A expression
2015-03-19

In a large patient cohort and in a robust animal model, we show that although LDHA expression varies biphasically during melanoma brain metastasis formation, tumor progression and survival seem to be functionally independent of LDHA.
Electrothermal behavior and terahertz emission properties of a planar array of two Bi2Sr2CaCu2O8+δintrinsic Josephson junction stacks
2015-03-19

We report on the investigation of the electrothermal behavior and the terahertz (THz) emission properties of two nearby Bi2Sr2CaCu2O (BSCCO) intrinsic Josephson junction stacks, using a combination of electric transport and THz emission measurements plus low temperature scanning laser microscopy. We start with a compact BSCCO stack (placed in a z-shaped structure between two BSCCO electrodes) with lateral dimensions of and height, consisting of about 480 junctions. After characterization, a 200 nm wide slit was introduced by focused ion beam milling, splitting the stack into two halves connected by continuous superconducting electrodes. In a third step, the upper electrode was also split, leading to a structure where the two stacks can be biased separately. In all configurations hot-spot formation was observed. Despite the separation into two stacks only a single hot spot formed, which, depending on the bias condition, could either be located in one of the stacks or extend into both stacks with its center in the slit. In none of the structures it was possible to achieve mutual synchronization of the two stacks, indicating that additional synchronizing elements or the presence of a base crystal as for mesa structures may be necessary for the operation of parallel array structures.
Open Labware: 3-D Printing Your Own Lab Equipment
2015-03-20

The introduction of affordable, consumer-oriented 3-D printers is a milestone in the current "maker movement," which has been heralded as the next industrial revolution. Combined with free and open sharing of detailed design blueprints and accessible development tools, rapid prototypes of complex products can now be assembled in one's own garage--a game-changer reminiscent of the early days of personal computing. At the same time, 3-D printing has also allowed the scientific and engineering community to build the "little things" that help a lab get up and running much faster and easier than ever before.
Selective Insulin Resistance in Homeostatic and Cognitive Control Brain Areas in Overweight and Obese Adults
2015-03-20

OBJECTIVE Impaired brain insulin action has been linked to obesity, type 2 diabetes, and neurodegenerative diseases. To date, the central nervous effects of insulin in obese humans still remain ill defined, and no study thus far has evaluated the specific brain areas affected by insulin resistance. RESEARCH DESIGN AND METHODS In 25 healthy lean and 23 overweight/obese participants, we performed magnetic resonance imaging to measure cerebral blood flow (CBF) before and 15 and 30 min after application of intranasal insulin or placebo. Additionally, participants explicitly rated pictures of high-caloric savory and sweet food 60 min after the spray for wanting and liking. RESULTS In response to insulin compared with placebo, we found a significant CBF decrease in the hypothalamus in both lean and overweight/obese participants. The magnitude of this response correlated with visceral adipose tissue independent of other fat compartments. Furthermore, we observed a differential response in the lean compared with the overweight/obese group in the prefrontal cortex, resulting in an insulin-induced CBF reduction in lean participants only. This prefrontal cortex response significantly correlated with peripheral insulin sensitivity and eating behavior measures such as disinhibition and food craving. Behaviorally, we were able to observe a significant reduction for the wanting of sweet foods after insulin application in lean men only. CONCLUSIONS Brain insulin action was selectively impaired in the prefrontal cortex in overweight and obese adults and in the hypothalamus in participants with high visceral adipose tissue, potentially promoting an altered homeostatic set point and reduced inhibitory control contributing to overeating behavior.
Impaired retrograde transport by the Dynein/Dynactin complex contributes to Tau-induced toxicity
2015-03-20

The gene mapt codes for the microtubule-associated protein Tau. The R406W amino acid substitution in Tau is associated with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) characterized by Tau-positive filamentous inclusions. These filamentous Tau inclusions are present in a group of neurodegenerative diseases known as tauopathies, including Alzheimer's disease (AD). To gain more insights into the pathomechanism of tauopathies, we performed an RNAi-based large-scale screen in Drosophila melanogaster to identify genetic modifiers of Tau[R406W]-induced toxicity. A collection of RNAi lines, putatively silencing more than 7000 genes, was screened for the ability to modify Tau[R406W]-induced toxicity in vivo. This collection covered more than 50% of all protein coding fly genes and more than 90% of all fly genes known to have a human ortholog. Hereby, we identified 62 genes that, when silenced by RNAi, modified Tau-induced toxicity specifically. Among these 62 modifiers were three subunits of the Dynein/Dynactin complex. Analysis on segmental nerves of fly larvae showed that pan neural Tau[R406W] expression and concomitant silencing of Dynein/Dynactin complex members synergistically caused strong pathological changes within the axonal compartment, but only minor changes at synapses. At the larval stage, these alterations did not cause locomotion deficits, but became evident in adult flies. Our data suggest that Tau-induced detrimental effects most likely originate from axonal rather than synaptic dysfunction and that impaired retrograde transport intensifies detrimental effects of Tau in axons. In conclusion, our findings contribute to the elucidation of disease mechanisms in tauopathies like FTDP-17 or AD.