julilili42/papers huggingface dataset:
Step-By-Step Instructions for Retina Recordings with Perforated Multi Electrode Arrays
2014-08-28

Multi-electrode arrays are a state-of-the-art tool in electrophysiology, also in retina research. The output cells of the retina, the retinal ganglion cells, form a monolayer in many species and are well accessible due to their proximity to the inner retinal surface. This structure has allowed the use of multi-electrode arrays for high-throughput, parallel recordings of retinal responses to presented visual stimuli, and has led to significant new insights into retinal organization and function. However, using conventional arrays where electrodes are embedded into a glass or ceramic plate can be associated with three main problems: (1) low signal-to-noise ratio due to poor contact between electrodes and tissue, especially in the case of strongly curved retinas from small animals, e.g. rodents; (2) insufficient oxygen and nutrient supply to cells located on the bottom of the recording chamber; and (3) displacement of the tissue during recordings. Perforated multi-electrode arrays (pMEAs) have been found to alleviate all three issues in brain slice recordings. Over the last years, we have been using such perforated arrays to study light evoked activity in the retinas of various species including mouse, pig, and human. In this article, we provide detailed step-by-step instructions for the use of perforated MEAs to record visual responses from the retina, including spike recordings from retinal ganglion cells and in vitro electroretinograms (ERG). In addition, we provide in-depth technical and methodological troubleshooting information, and show example recordings of good quality as well as examples for the various problems which might be encountered. While our description is based on the specific equipment we use in our own lab, it may also prove useful when establishing retinal MEA recordings with other equipment.
Identification and characterization of novel associations in the CASP8/ALS2CR12 region on chromosome 2 with breast cancer risk
2014-08-28

Previous studies have suggested that polymorphisms in CASP8 on chromosome 2 are associated with breast cancer risk. To clarify the role of CASP8 in breast cancer susceptibility, we carried out dense genotyping of this region in the Breast Cancer Association Consortium (BCAC). Single-nucleotide polymorphisms (SNPs) spanning a 1 Mb region around CASP8 were genotyped in 46 450 breast cancer cases and 42 600 controls of European origin from 41 studies participating in the BCAC as part of a custom genotyping array experiment (iCOGS). Missing genotypes and SNPs were imputed and, after quality exclusions, 501 typed and 1232 imputed SNPs were included in logistic regression models adjusting for study and ancestry principal components. The SNPs retained in the final model were investigated further in data from nine genome-wide association studies (GWAS) comprising in total 10 052 case and 12 575 control subjects. The most significant association signal observed in European subjects was for the imputed intronic SNP rs1830298 in ALS2CR12 (telomeric to CASP8), with per allele odds ratio and 95% confidence interval [OR (95% confidence interval, CI)] for the minor allele of 1.05 (1.03-1.07), P = 1 × 10(-5). Three additional independent signals from intronic SNPs were identified, in CASP8 (rs36043647), ALS2CR11 (rs59278883) and CFLAR (rs7558475). The association with rs1830298 was replicated in the imputed results from the combined GWAS (P = 3 × 10(-6)), yielding a combined OR (95% CI) of 1.06 (1.04-1.08), P = 1 × 10(-9). Analyses of gene expression associations in peripheral blood and normal breast tissue indicate that CASP8 might be the target gene, suggesting a mechanism involving apoptosis.
Ginkgo biloba Extract EGb 761® in Children with ADHD
2014-08-28

Objectives: The side effects, nonresponse, and prejudices against conventional pharmacological treatments call for complementary or alternative medical treatments (CAM) for ADHD. One possible treatment, at least for cognitive problems, might be the administration of Ginkgo biloba, though evidence is currently rare. This study tests the clinical efficacy of a Ginkgo biloba special extract (EGb 761 ® ) and its correlation with brain electrical activity in children with ADHD combined type according to DSM-IV. Method: In this open clinical pilot study, EGb 761 ® was administered to 20 children with ADHD over 3 to 5 weeks. Dosage was increased to a maximum of 240 mg daily if attention problems persisted. Possible drug side effects were assessed using the Side Effect Rating Scale. Efficacy was assessed in a multilevel approach including clinical assessment, quality of life (QoL), as well as performance and preparatory brain-electrical activity evoked during a Continuous Performance Test (Cue-CNV in the CPT). Results: A very low rate of mild adverse effects occurred during the observation period. Following EGb 761 ® administration, possible improvements in QoL, ADHD core symptoms as well as CPT performance were detected. Improved core symptoms were positively related to elevated CNV amplitude. Conclusion: This preliminary evidence suggests that EGb 761 ® at a maximal dosage of 240 mg daily might be a clinically useful alternative treatment for children with ADHD, but further evidence is required before firm conclusions can be made.
Reactivity of boryllithium with AlMe3, AlEt3, and GaMe3, including the synthesis of a lanthanum heterogallate complex
2014-08-28

Treatment of boryllithium (THF)2Li[B(NDippCH)2] (Dipp = 2,6-diisopropylphenyl) with various amounts of AlMe3 or GaMe3 leads to the formation of inter group 13 compounds. Equimolar reactions result in ate complexes of the type (THF)nLi(Me3M)[B(NDippCH)2] (M = Al, Ga) with discrete (n = 2, 3) or eight-membered ring structures (n = 1). We reported previously that use of excessive amounts of group 13 metal methyl compounds can result in four-coordinate THF-adducts (THF)(Me2M)[B(NDippCH)2] or unsolvated complexes {(Me2M)[B(NDippCH)2]}x (M = Al, x = 2; M = Ga, x = 1) via separation of LiMMe4. Polymeric [(THF)Li(Et3Al){B(NDippCH)2}]n is formed when boryllithium is reacted with an equimolar amount of AlEt3. The discrete THF-adduct (THF)Et2Al[B(NDippCH)2] can be isolated when using a boryllithium/AlEt3 ratio of 1 : 5. The reaction of THF-adduct (THF)Me2Ga[B(NDippCH)2] with La(AlMe4)3 affords the heterogallate complex La[(Me3Ga){B(NDippCH)2}]3, according to a donor-assisted tetramethylaluminate/alkylgallate exchange. The obtained complexes feature rare examples of crystallographically characterized non-cluster compounds with unsupported B-Al and B-Ga contacts.
Extending the functions of scanning near-field optical microscopy
2014-08-28

Advanced optical setups are continuously developed to gain deeper insight into microscopic matter. In this paper we report the expansion of a home-built parabolic mirror assisted scanning, near-field optical microscope (PMSNOM) by introducing four complementary functions. 1) We integrated a scanning tunneling feedback function in addition to an already existent shear-force feedback control mechanism. Hence a scanning tunneling microscope (STM)-SNOM is realized whose performance will be demonstrated by the tip-enhanced Raman peaks of graphene sheets on a copper substrate. 2) We integrated an ultrafast laser system into the microscope which allows us to combine nonlinear optical microscopy with hyperspectral SNOM imaging. This particular expansion was used to study influences of plasmonic resonances on nonlinear optical properties of metallic nanostructures. 3) We implemented a polarization angle resolved detection technique which enables us to analyze the local structural order of α-sexithiophene (α-6T). 4) We combined scanning photocurrent microscopy with the microscope. This allows us to study morphology related optical (Raman and photoluminescence) and electrical properties of optoelectronic systems. Our work demonstrates the great potential of turning a SNOM into an advanced multifunctional microscope.
Inside Cover: Site‐Directed RNA Editing with Antagomir Deaminases — A Tool to Study Protein and RNA Function (ChemMedChem 9/2014)
2014-08-28

The inside-front cover picture shows transcript repair by site-directed A-to-I RNA editing inside mammalian cells. Lipofected antagomirs steer an engineered deaminase specifically to the mRNA substrate and activate cyan fluorescent protein (CFP) fluorescence by reprogramming a premature STOP codon to tryptophan. The tool is applicable in medicine and biology. The assembly strategy may serve as a general blue-print in synthetic biology and nanobiotechnology. For more details, see the Concept by Paul Vogel and Thorsten Stafforst on p. 2021 ff.
Cox Rings
2014-08-29

Cox rings are significant global invariants of algebraic varieties, naturally generalizing homogeneous coordinate rings of projective spaces. This book provides a largely self-contained introduction to Cox rings, with a particular focus on concrete aspects of the theory. Besides the rigorous presentation of the basic concepts, other central topics include the case of finitely generated Cox rings and its relation to toric geometry; various classes of varieties with group actions; the surface case; and applications in arithmetic problems, in particular Manin's conjecture. The introductory chapters require only basic knowledge in algebraic geometry. The more advanced chapters also touch on algebraic groups, surface theory, and arithmetic geometry. Each chapter ends with exercises and problems. These comprise mini-tutorials and examples complementing the text, guided exercises for topics not discussed in the text, and, finally, several open problems of varying difficulty.
Natural polyphenols binding to amyloid: A broad class of compounds to treat different human amyloid diseases
2014-08-29

Polyphenols are a large group of phytonutrients found in herbal beverages and foods. They have manifold biological activities, including antioxidative, antimicrobial, and anti‐inflammatory properties. Interestingly, some polyphenols bind to amyloid and substantially ameliorate amyloid diseases. Misfolding, aggregation, and accumulation of amyloid fibrils in tissues or organs leads to a group of disorders, called amyloidoses. Prominent diseases are Alzheimer's, Parkinson's, and Huntington's disease, but there are other, less well‐known diseases wherein accumulation of misfolded protein is a prominent feature. Amyloidoses are a major burden to public health. In particular, Alzheimer's disease shows a strong increase in patient numbers. Accelerated development of effective therapies for amyloidoses is a necessity. A viable strategy can be the prevention or reduction of protein misfolding, thus reducing amyloid build‐up by restoring the cellular aggretome. Amyloid‐binding polyphenols affect amyloid formation on various levels, e.g. by inhibiting fibril formation or steering oligomer formation into unstructured, nontoxic pathways. Consequently, preclinical studies demonstrate reduction of amyloid‐formation by polyphenols. Amyloid‐binding polyphenols might be suitable lead structures for development of imaging agents for early detection of disease and monitoring amyloid deposition. Intake of dietary polyphenols might be relevant to the prevention of amyloidoses. Nutraceutical strategies might be a way to reduce amyloid diseases.
Characterization of Sleep in Aplysia californica
2014-08-29

Resting behavior in Aplysia fulfills all invertebrate characteristics of sleep including: (1) a specific sleep body posture, (2) preferred resting location, (3) reversible behavioral quiescence, (4) elevated arousal thresholds for sensory stimuli during sleep, and (5) compensatory sleep rebound after sleep deprivation.
Quantitative Phosphoproteomics of MurineFmr1-KO Cell Lines Provides New Insights into FMRP-Dependent Signal Transduction Mechanisms
2014-08-29

Fragile X mental retardation protein (FMRP) is an RNA-binding protein that has a major effect on neuronal protein synthesis. Transcriptional silencing of the FMR1 gene leads to loss of FMRP and development of Fragile X syndrome (FXS), the most common known hereditary cause of intellectual impairment and autism. Here we utilize SILAC-based quantitative phosphoproteomics to analyze murine FMR1(-) and FMR1(+) fibroblastic cell lines derived from FMR1-KO embryos to identify proteins and phosphorylation sites dysregulated as a consequence of FMRP loss. We quantify FMRP-related changes in the levels of 5,023 proteins and 6,133 phosphorylation events and map them onto major signal transduction pathways. Our study confirms global downregulation of the MAPK/ERK pathway and decrease in phosphorylation level of ERK1/2 in the absence of FMRP, which is connected to attenuation of long-term potentiation. We detect differential expression of several key proteins from the p53 pathway, pointing to the involvement of p53 signaling in dysregulated cell cycle control in FXS. Finally, we detect differential expression and phosphorylation of proteins involved in pre-mRNA processing and nuclear transport, as well as Wnt and calcium signaling, such as PLC, PKC, NFAT, and cPLA2. We postulate that calcium homeostasis is likely affected in molecular pathogenesis of FXS.
Nanoprobe crystallographic orientation studies of isolated shield elements of the coccolithophore species Emiliania huxleyi
2014-08-29

Coccolithophore algae produce elaborately structured skeletons composed of sub-micrometer-scale calcite crystals. In order to understand calcite crystallization and assembly in a coccosphere with nanoscale resolution, the crystal orientation and interdigitation of the structural units were investigated by transmission electron microscopy imaging, selected-area and nano-probe electron diffraction. Focused ion beam sectioning of coccoliths of the coccolithophore species Emiliania huxleyi is used to obtain target-prepared specimens in suitable orientation. We were able to detect and analyze the V-unit, which is overgrown by the R-unit. For the V-unit the 001 direction points perpendicular to the coccolith plane while the 110 axis is tangential to the coccolith ring. The R-unit c-axis is parallel and the b-axis is perpendicular to the coccolith plane, thus confirming the R- and V-model which was based on scanning electron microscopy and optical microscopy. Furthermore we show that the distal- and the proximal shield element of an individual R-unit of a single segment are tilted by 4 degrees +/- 1 degrees with respect to each other. This orientation change is required to obtain the flat domed character of the coccoliths, which is necessary to form the coccosphere. The orientation change between the distal- and the proximal shield element appears continuous.
Cerebral Processing of Prosodic Emotional Signals: Evaluation of a Network Model Using rTMS
2014-08-29

A great number of functional imaging studies contributed to developing a cerebral network model illustrating the processing of prosody in the brain. According to this model, the processing of prosodic emotional signals is divided into three main steps, each related to different brain areas. The present study sought to evaluate parts of the aforementioned model by using low-frequency repetitive transcranial magnetic stimulation (rTMS) over two important brain regions identified by the model: the superior temporal cortex (Experiment 1) and the inferior frontal cortex (Experiment 2). The aim of both experiments was to reduce cortical activity in the respective brain areas and evaluate whether these reductions lead to measurable behavioral effects during prosody processing. However, results obtained in this study revealed no rTMS effects on the acquired behavioral data. Possible explanations for these findings are discussed in the paper.
Recurrence and Transience of Critical Branching Processes in Random Environment with Immigration and an Application to Excited Random Walks
2014-08-29

We establish recurrence and transience criteria for critical branching processes in random environments with immigration. These results are then applied to the recurrence and transience of a recurrent random walk in a random environment on Z disturbed by cookies inducing a drift to the right of strength 1.
Arithmetic applications
2014-08-29

In Section 6.1, we give an overview of the theory of universal torsors over arbitrary fields of characteristic zero. Furthermore, we explore their connection to characteristic spaces and Cox rings. Section 6.2 deals with the existence of rational points over number fields. We discuss the Hasse principle and weak approximation. The failure of these principles is often explained by Brauer–Manin obstructions. We indicate how this can be approached via universal torsors and give an overview of the existing results. Section 6.3 is devoted to the distribution of rational points on varieties over number fields. Here, one introduces height functions on the set of rational points and is interested mainly in the asymptotic behavior of the number of rational points of bounded height. For Fano varieties, this behavior is predicted by Manin's conjecture. We indicate how universal torsors and Cox rings can be applied to prove Manin's conjucture. In Section 6.4, we specialize to del Pezzo surfaces. Here, Manin's conjecture is known in many cases, and a general strategy emerges. We discuss this strategy and some technical ingredients in detail. In Section 6.5, we show how it can be applied to prove Manin's conjecture for a singular cubic surface.
Toric varieties and Gale duality
2014-08-29

Toric varieties form an important class of examples in algebraic geometry, as they admit a complete description in terms of combinatorial data, so-called lattice fans. In Section 2.1, we briefly recall this description and also some of the basic facts in toric geometry. Then we present Cox's construction of the characteristic space of a toric variety in terms of a defining fan and discuss the basic geometry around this. Section 2.2 is pure combinatorics. We introduce the notion of a “bunch of cones” and show that, in an appropriate setting, this is the Gale dual version of a fan. Under this duality, the normal fans of polytopes correspond to bunches of cones arising canonically from the chambers of the so-called Gelfand–Kapranov–Zelevinsky decomposition. In Section 2.3, we discuss the geometric meaning of bunches of cones: they encode the maximal separated good quotients for subgroups of the acting torus on an affine toric variety. In Section 2.4, we specialize these considerations to toric characteristic spaces, that is, to the good quotients arising from Cox's construction. This leads to an alternative combinatorial description of toric varieties in terms of “lattice bunches,” which turns out to be particularly suitable for phenomena around divisors.
Selected topics
2014-08-29

We discuss various topics around Cox rings. The first section is devoted to birational maps, for example, blow-ups. We figure out the class of modifications that preserve finite generation and we show how to compute the Cox ring of the modified variety in terms of the Cox ring of the initial one. In Section 4.2, we first introduce a class of quotient presentations dominated by the characteristic space and comprising, for example, the classical affine cones. Then we provide a lifting result for connected subgroups of the automorphism group. In the case of a finitely generated Cox ring, this gives an approach to the whole automorphism group, showing in particular that it is affine algebraic. The topic of Section 4.3 is finite generation of the Cox ring. We provide general criteria and characterizations; for example, the finiteness characterization of Hu and Keel in terms of polyhedral subdivisions of the moving cone is proven and we discuss finite generation of the Cox ring for Fano varieties. In Section 4.4 we consider varieties coming with a torus action. We express their Cox ring in terms of data of the action. In the case of a rational variety with an action of complexity 1, we see that the Cox ring is given by trinomial relations as in Section 3.4. In particular, the constructions given there produce indeed all rational normal complete A2-varieties with a torus action of complexity 1. Section 4.5 is about almost homogeneous varieties, that is, equivariant open embeddings of homogeneous spaces. We first describe the Cox ring of a homogeneous space G/H. Embeddings X of homogeneous spaces G/H with finitely generated Cox ring and small boundary X \\ G/H allow an immediate description via bunched rings and provide a rich example class. Finally, we survey in this section results on the case of wonderful and more general spherical varieties.
Na+ current properties in islet α‐ and β‐cells reflect cell‐specific Scn3a and Scn9a expression
2014-08-30

Key points α‐ and β‐cells express both Na v 1.3 and Na v 1.7 Na + channels but in different relative amounts. The differential expression explains the different properties of Na + currents in α‐ and β‐cells. Na v 1.3 is the functionally important Na + channel α subunit in both α‐ and β‐cells. Islet Na v 1.7 channels are locked in an inactive state due to an islet cell‐specific factor. Mouse pancreatic β‐ and α‐cells are equipped with voltage‐gated Na + currents that inactivate over widely different membrane potentials (half‐maximal inactivation ( V 0.5 ) at −100 mV and −50 mV in β‐ and α‐cells, respectively). Single‐cell PCR analyses show that both α‐ and β‐cells have Na v 1.3 ( Scn3 ) and Na v 1.7 ( Scn9a ) α subunits, but their relative proportions differ: β‐cells principally express Na v 1.7 and α‐cells Na v 1.3. In α‐cells, genetically ablating Scn3a reduces the Na + current by 80%. In β‐cells, knockout of Scn9a lowers the Na + current by &gt;85%, unveiling a small Scn3a ‐dependent component. Glucagon and insulin secretion are inhibited in Scn3a −/− islets but unaffected in Scn9a‐ deficient islets. Thus, Na v 1.3 is the functionally important Na + channel α subunit in both α‐ and β‐cells because Na v 1.7 is largely inactive at physiological membrane potentials due to its unusually negative voltage dependence of inactivation. Interestingly, the Na v 1.7 sequence in brain and islets is identical and yet the V 0.5 for inactivation is &gt;30 mV more negative in β‐cells. This may indicate the presence of an intracellular factor that modulates the voltage dependence of inactivation.
Current concepts: host–pathogen interactions in cystic fibrosis airways disease
2014-08-31

Chronic infection and inflammation are defining characteristics of cystic fibrosis (CF) airway disease. Conditions within the airways of patients living with CF are conducive to colonisation by a variety of opportunistic bacterial, viral and fungal pathogens. Improved molecular identification of microorganisms has begun to emphasise the polymicrobial nature of infections in the CF airway microenvironment. Changes to CF airway physiology through loss of cystic fibrosis transmembrane conductance regulator functionality result in a wide range of immune dysfunctions, which permit pathogen colonisation and persistence. This review will summarise the current understanding of how CF pathogens infect, interact with and evade the CF host.