julilili42/papers huggingface dataset:
Probability density function of steady state concentration in two‐dimensional heterogeneous porous media
2011-10-13

Spatial variability of hydraulic aquifer parameters causes meandering, squeezing, stretching, and enhanced mixing of steady state plumes in concentrated hot‐spots of mixing. Because the exact spatial distribution of hydraulic parameters is uncertain, the spatial distribution of enhanced mixing rates is also uncertain. We discuss how relevant the resulting uncertainty of mixing rates is for predicting concentrations. We develop analytical solutions for the full statistical distribution of steady state concentration in two‐dimensional, statistically uniform domains with log‐hydraulic conductivity following an isotropic exponential model. In particular, we analyze concentration statistics at the fringes of wide plumes, conceptually represented by a solute introduced over half the width of the domain. Our framework explicitly accounts for uncertainty of streamline meandering and uncertainty of effective transverse mixing (defined at the Darcy scale). We make use of existing low‐order closed‐form expressions that lead to analytical expressions for the statistical distribution of local concentration values. Along the expected position of the plume fringe, the concentration distribution strongly clusters at its extreme values. This behavior extends over travel distances of up to tens of integral scales for the parameters tested in our study. In this regime, the uncertainty of effective transverse mixing is substantial enough to have noticeable effects on the concentration probability density function. At significantly larger travel distances, intermediate concentration values become most likely, and uncertainty of effective transverse mixing becomes negligible. A comparison to numerical Monte Carlo simulations of flow and solute transport show excellent agreement with the theoretically derived expressions.
Structural and Phylogenetic Analyses of the GP42 Transglutaminase from Phytophthora sojae Reveal an Evolutionary Relationship between Oomycetes and Marine Vibrio Bacteria
2011-10-13

Transglutaminases (TGases) are ubiquitous enzymes that catalyze selective cross-linking between protein-bound glutamine and lysine residues; the resulting isopeptide bond confers high resistance to proteolysis. Phytophthora sojae, a pathogen of soybean, secretes a Ca(2+)-dependent TGase (GP42) that is activating defense responses in both host and non-host plants. A GP42 fragment of 13 amino acids, termed Pep-13, was shown to be absolutely indispensable for both TGase and elicitor activity. GP42 does not share significant primary sequence similarity with known TGases from mammals or bacteria. This suggests that GP42 has evolved novel structural and catalytic features to support enzymatic activity. We have solved the crystal structure of the catalytically inactive point mutant GP42 (C290S) at 2.95 Å resolution and identified residues involved in catalysis by mutational analysis. The protein comprises three domains that assemble into an elongated structure. Although GP42 has no structural homolog, its core region displays significant similarity to the catalytic core of the Mac-1 cysteine protease from Group A Streptococcus, a member of the papain-like superfamily of cysteine proteases. Proteins that are taxonomically related to GP42 are only present in plant pathogenic oomycetes belonging to the order of the Peronosporales (e.g. Phytophthora, Hyaloperonospora, and Pythium spp.) and in marine Vibrio bacteria. This suggests that a lateral gene transfer event may have occurred between bacteria and oomycetes. Our results offer a basis to design and use highly specific inhibitors of the GP42-like TGase family that may impair the growth of important oomycete and bacterial pathogens.
Inhibitory transcranial magnetic theta burst stimulation attenuates prefrontal cortex oxygenation
2011-10-14

Abstract Recent studies highlighted the great potential of newly established theta burst stimulation (TBS) protocols for non‐invasive human brain stimulation studies using transcranial magnetic stimulation (TMS). While intermittent TBS over the primary motor cortex was found to potentiate motor evoked potentials, continuous TBS led to profound attenuations. Although numerous studies investigated the impact of TBS on motor cortex function, yet, only few imaging studies focused on its effects in other brain areas. Particularly for the prefrontal cortex, it is unclear whether TBS has similar effects compared to application over motor areas. In the current study continuous TBS was applied to either the left or right dorsolateral prefrontal cortex in a sample of healthy subjects. Changes in prefrontal oxygenation were measured during an emotional Stroop task by means of functional multi‐channel near‐infrared spectroscopy (fNIRS) before and after stimulation. Results showed bilaterally decreased prefrontal oxygenation following inhibitory stimulation of the left prefrontal cortex but no behavioral effect. No such alterations were observed following right‐hemispheric or sham stimulation. The results of the current study are in line with earlier findings and additionally demonstrate that also prefrontal oxygenation can be impaired by continuous TBS. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.
Stoichiometry Controlled, Single‐Crystalline Bi2Te3 Nanowires for Transport in the Basal Plane
2011-10-14

Abstract Thermoelectric Bi 2 Te 3 based bulk materials are widely used for solid‐state refrigeration and power‐generation at room temperature. For low‐dimensional and nanostructured thermoelectric materials an increase of the thermoelectric figure of merit ZT is predicted due to quantum confinement and phonon scattering at interfaces. Therefore, the fabrication of Bi 2 Te 3 nanowires, thin films, and nanostructured bulk materials has become an important and active field of research. Stoichiometric Bi 2 Te 3 nanowires with diameters of 50–80 nm and a length of 56 μm are grown by a potential‐pulsed electrochemical deposition in a nanostructured Al 2 O 3 matrix. By transmission electron microscopy (TEM), dark‐field images together with electron diffraction reveal single‐crystalline wires, no grain boundaries can be detected. The stoichiometry control of the wires by high‐accuracy, quantitative enegy‐dispersive X‐ray spectroscopy (EDX) in the TEM instrument is of paramount importance for successfully implementing the growth technology. Combined electron diffraction and EDX spectroscopy in the TEM unambiguously prove the correct crystal structure and stoichiometry of the Bi 2 Te 3 nanowires. X‐ray and electron diffraction reveal growth along the [110] and [210] directions and the c axis of the Bi 2 Te 3 structure lies perpendicular to the wire axis. For the first time single crystalline, stoichiometric Bi 2 Te 3 nanowires are grown that allow transport in the basal plane without being affected by grain boundaries.
Altered stress stimulation of inward rectifier potassium channels in Andersen‐Tawil syndrome
2011-10-14

ABSTRACT Inward rectifier potassium channels of the Kir2 subfamily are important determinants of the electrical activity of brain and muscle cells. Genetic mutations in Kir2.1 associate with Andersen‐Tawil syndrome (ATS), a familial disorder leading to stress‐triggered periodic paralysis and ventricular arrhythmia. To identify the molecular mechanisms of this stress trigger, we analyze Kir channel function and localization electrophysiologically and by time‐resolved confocal microscopy. Furthermore, we employ a mathematical model of muscular membrane potential. We identify a novel corticoid signaling pathway that, when activated by glucocorticoids, leads to enrichment of Kir2 channels in the plasma membranes of mammalian cell lines and isolated cardiac and skeletal muscle cells. We further demonstrate that activation of this pathway can either partly restore (40% of cases) or further impair (20% of cases) the function of mutant ATS channels, depending on the particular Kir2.1 mutation. This means that glucocorticoid treatment might either alleviate or deteriorate symptoms of ATS depending on the patient's individual Kir2.1 genotype. Thus, our findings provide a possible explanation for the contradictory effects of glucocorticoid treatment on symptoms in patients with ATS and may open new pathways for the design of personalized medicines in ATS therapy.—Seebohm, G., Strutz‐Seebohm, N., Ursu, O. N., Preisig‐Müller, R., Zuzarte, M., Hill, E. V., Kienitz, M.‐C., Bendahhou, S., Fauler, M., Tapken, D., Decher, N., Collins, A., Jurkat‐Rott, K., Steinmeyer, K., Lehmann‐Horn, F., Daut, J., Tavaré, J. M., Pott, L., Bloch,W., Lang, F. Altered stress stimulation of inward rectifier potassium channels in Andersen‐Tawil syndrome. FASEB J. 26, 513–522 (2012). www.fasebj.org
Novel GDI1 mutation in a large family with nonsyndromic X‐linked intellectual disability
2011-10-14

Abstract X‐linked intellectual disability (XLID) is a heterogeneous disorder, and mutations in more than 90 genes have been associated with XLID to date. We report on a large multi‐generational German family in which the affected male family members had nonsyndromic intellectual disability, that is, they had neither abnormal body measurements nor any other significant clinical problems. Molecular genetic analysis revealed a frameshift mutation in GDI1 (c.1185_1186delAG; Ser396ProfsX15) that co‐segregated with the disease. GDI1 encodes for the GDP‐dissociation inhibitor alpha (αGDI), a protein involved in the regulation of the activity of Rab GTPases. Only three families with GDI1 mutations have been reported so far. The present family supports the lack of additional phenotypic features in patients with GDI1 mutations, rendering a clinical diagnosis of GDI1 ‐associated XLID impossible. Thus, this family not only broadens the spectrum of GDI1 mutations but also emphasizes the need for parallel testing of all known genes associated with ID in patients with an unspecific phenotype. © 2011 Wiley Periodicals, Inc.
Effects of Aversive Stimuli on Prospective Memory. An Event-Related fMRI Study
2011-10-17

Prospective memory (PM) describes the ability to execute a previously planned action at the appropriate point in time. Although behavioral studies clearly showed that prospective memory performance is affected by the emotional significance attributed to the intended action, no study so far investigated the brain mechanisms subserving the modulatory effect of emotional salience on PM performance. The general aim of the present study was to explore brain regions involved in prospective memory processes when PM cues are associated with emotional stimuli. In particular, based on the hypothesised critical role of the prefrontal cortex in prospective memory in the presence of emotionally salient stimuli, we expected a stronger involvement of aPFC when the retrieval and execution of the intended action is cued by an aversive stimulus. To this aim BOLD responses of PM trials cued by aversive facial expressions were compared to PM trials cued by neutral facial expressions. Whole brain analysis showed that PM task cued by aversive stimuli is differentially associated with activity in the right lateral prefrontal area (BA 10) and in the left caudate nucleus. Moreover a temporal shift between the response of the caudate nucleus that preceded that of aPFC was observed. These findings suggest that the caudate nucleus might provide an early analysis of the affective properties of the stimuli, whereas the anterior lateral prefrontal cortex (BA10) would be involved in a slower and more deliberative analysis to guide goal-directed behaviour.
First Results of Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Children
2011-10-18

The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).
Guilty of a Fault that one has not Committed. The Limits of the Group-Based Sanction Policy Carried out by the Commission and the European Courts in EU-Antitrust Law
2011-10-18

The economic entity doctrine allows the Commission to fine a parent company if its subsidiary has infringed the competition rules. In such cases, the Commission holds the subsidiary and the parent jointly and severally liable. The EU Courts have acknowledged this sanctioning concept as based on an interpretation of the notion of “undertaking”. Group companies are deemed to form one unitary undertaking in terms of the competition rules. However, the economic entity doctrine faces increasing criticism. It is argued that being a parent can hardly suffice to establish liability for the infringement of the subsidiary. Also, the rule stating that a 100 % shareholder is presumed to form an economic entity with its subsidiary is seen to conflict with the in dubio pro reo principle. As far as joint and several liability is concerned, practical problems arise with respect to recourse litigation between the corporate entities. The practical significance of the problems is rising. Although the Court of Justice has espoused the economic entity doctrine, there are reports that a Dutch company has recently asked the European Court of Human Rights to rule on whether such a concept is compatible with the presumption of innocence. Moreover, the national Courts struggle with the problem of how to apportion liability between the jointly and severally liable group companies with respect to recourse claims. The General Court has recently tried to establish general principles in that respect in its Siemens/VA Tech judgment which, however, seem to have created further problems.
A pragmatic approach to XML interoperability – the Component Metadata Infrastructure (CMDI)
2011-10-20

XML has been designed for creating structured documents, but the information that is encoded in these structures are, by definition, out of scope for XML. Additional sources, normally not easily interpretable by computers, such as documentation are needed to determine the intention of specific tags in a tag-set. The Component Metadata Infrastructure (CMDI) takes a rather pragmatic approach to foster interoperability between XML instances in the domain of metadata descriptions for language resources. This paper gives an overview of this approach.
Discovery of extended VHEγ-ray emission from the vicinity of the young massive stellar cluster Westerlund 1
2011-10-20

Aims. Results obtained in very-high-energy (VHE; E ≥ 100 GeV) γ-ray observations performed with the H.E.S.S. telescope array are used to investigate particle acceleration processes in the vicinity of the young massive stellar cluster Westerlund 1 (Wd 1).&#13;\\n&#13;\\nMethods. Imaging of Cherenkov light from γ-ray induced particle cascades in the Earth’s atmosphere is used to search for VHE γ rays from the region around Wd 1. Possible catalogued counterparts are searched for and discussed in terms of morphology and energetics of the H.E.S.S. source.&#13;\\n&#13;\\nResults. The detection of the degree-scale extended VHE γ-ray source HESS J1646–458 is reported based on 45 h of H.E.S.S. observations performed between 2004 and 2008. The VHE γ-ray source is centred on the nominal position of Wd 1 and detected with a total statistical significance of ~20σ. The emission region clearly extends beyond the H.E.S.S. point-spread function (PSF). The differential energy spectrum follows a power law in energy with an index of Γ = 2.19 ± 0.08stat ± 0.20sys and a flux normalisation at 1 TeV of Φ0 = (9.0 ± 1.4stat ± 1.8sys) × 10-12 TeV-1 cm-2 s-1. The integral flux above 0.2 TeV amounts to (5.2 ± 0.9) × 10-11 cm-2 s-1.&#13;\\n&#13;\\nConclusions. Four objects coincident with HESS J1646–458 are discussed in the search of a counterpart, namely the magnetar CXOU J164710.2 − 455216, the X-ray binary 4U 1642–45, the pulsar PSR J1648–4611 and the massive stellar cluster Wd 1. In a single-source scenario, Wd 1 is favoured as site of VHE particle acceleration. Here, a hadronic parent population would be accelerated within the stellar cluster. Beside this, there is evidence for a multi-source origin, where a scenario involving PSR J1648–4611 could be viable to explain parts of the VHE γ-ray emission of HESS J1646–458.
Paleotemperature and paleosalinity inferences and chemostratigraphy across the Aptian/Albian boundary in the subtropical North Atlantic
2011-10-20

Geochemical analyses of extraordinarily well preserved late Aptian–early Albian foraminifera from Blake Nose (Ocean Drilling Program Site 1049) reveal rapid shifts of δ 18 O, δ 13 C, and 87 Sr/ 88 Sr in the subtropical North Atlantic that may be linked to a major planktic foraminifer extinction event across the Aptian/Albian boundary. The abruptness of the observed geochemical shifts and their coincidence with a sharp lithologic contact is explained as an artifact of a previously undetected hiatus of 0.8–1.4 million years at the boundary contact, but the values before and after the hiatus indicate that major oceanographic changes occurred at this time. 87 Sr/ 88 Sr increase by ∼0.000 200, δ 13 C values decrease by 1.5‰ to 2.2‰, and δ 18 O values decrease by ∼1.0‰ (planktics) to 0.5‰ (benthics) across the hiatus. Further, both 87 Sr/ 88 Sr ratios and δ 18 O values during the Albian are anomalously high. The 87 Sr/ 88 Sr values deviate from known patterns to such a degree that an explanation requires either the presence of inter‐basin differences in seawater 87 Sr/ 88 Sr during the Albian or revision of the seawater curve. For δ 18 O, planktic values in some Aptian samples likely reflect a diagenetic overprint, but preservation is excellent in the rest of the section. In well preserved material, benthic foraminiferal values are largely between 0.5 and 0.0‰ and planktic samples are largely between 0.0‰ to −1.0‰, with a brief excursion to −2.0‰ during OAE 1b. Using standard assumptions for Cretaceous isotopic paleotemperature calculations, the δ 18 O values suggest bottom water temperatures (at ∼1000 –1500 m) of 8–10°C and surface temperatures of 10–14°C, which are 4–6°C and 10–16°C cooler, respectively, than present‐day conditions at the same latitude. The cool subtropical sea surface temperature estimates are especially problematic because other paleoclimate proxy data for the mid‐Cretaceous and climate model predictions suggest that subtropical sea surface temperatures should have been the same as or warmer than at present. Because of their exquisite preservation, whole scale alteration of the analyzed foraminifera is an untenable explanation. Our proposed solution is a high evaporative fractionation factor in the early Albian North Atlantic that resulted in surface waters with higher δ 18 O values at elevated salinities than commonly cited in Cretaceous studies. A high fractionation factor is consistent with high rates of vapor export and a vigorous hydrological cycle and, like the Sr isotopes, implies limited connectivity among the individual basins of the Early Cretaceous proto‐Atlantic ocean.
Synthesis of Chondramide A Analogues with Modified β‐Tyrosine and Their Biological Evaluation
2011-10-20

Abstract Starting from cinnamates 9 , obtained by Wittig reaction or Heck coupling, the diols 17 were prepared by asymmetric dihydroxylation. This was followed by a regioselective substitution of the 3‐OH group with hydrazoic acid under Mitsunobu conditions. Methylation of the 2‐OH group and reduction of the azide group led to the β‐tyrosine derivatives 8 . Condensation with the dipeptide acid 6 furnished the tripeptide part of the chondramides. The derived acids 21 were combined with the hydroxy ester 7 to the esters 22 . Cleavage of the tert ‐butyl groups and intramolecular lactam formation gave rise to the chondramide A analogues 2 b – k . Growth inhibition assays showed most of the analogues to be biologically active. Some of them even reach the activity of jasplakinolide. It can be concluded that the 4‐position of the aryl ring in the β‐tyrosine of chondramide A tolerates structural modifications quite well.
Adversarial machine learning
2011-10-21

In this paper (expanded from an invited talk at AISEC 2010), we discuss an emerging field of study: adversarial machine learning---the study of effective machine learning techniques against an adversarial opponent. In this paper, we: give a taxonomy for classifying attacks against online machine learning algorithms; discuss application-specific factors that limit an adversary's capabilities; introduce two models for modeling an adversary's capabilities; explore the limits of an adversary's knowledge about the algorithm, feature space, training, and input data; explore vulnerabilities in machine learning algorithms; discuss countermeasures against attacks; introduce the evasion challenge; and discuss privacy-preserving learning techniques.
Exogenous seeding of cerebral β‐amyloid deposition in βAPP‐transgenic rats
2011-10-21

J. Neurochem. (2012) 120 , 660–666. Abstract Deposition of the amyloid‐β (Aβ) peptide in senile plaques and cerebral Aβ angiopathy (CAA) can be stimulated in Aβ‐precursor protein (APP)‐transgenic mice by the intracerebral injection of dilute brain extracts containing aggregated Aβ seeds. Growing evidence implicates a prion‐like mechanism of corruptive protein templating in this phenomenon, in which aggregated Aβ itself is the seed. Unlike prion disease, which can be induced de novo in animals that are unlikely to spontaneously develop the disease, previous experiments with Aβ seeding have employed animal models that, as they age, eventually will generate Aβ lesions in the absence of seeding. In the present study, we first established that a transgenic rat model expressing human APP (APP21 line) does not manifest endogenous deposits of Aβ within the course of its median lifespan (30 months). Next, we injected 3‐month‐old APP21 rats intrahippocampally with dilute Alzheimer brain extracts containing aggregated Aβ. After a 9‐month incubation period, these rats had developed senile plaques and CAA in the injected hippocampus, whereas control rats remained free of such lesions. These findings underscore the co‐dependence of agent and host in governing seeded protein aggregation, and show that cerebral Aβ‐amyloidosis can be induced even in animals that are relatively refractory to the spontaneous origination of parenchymal and vascular deposits of Aβ.