julilili42/papers huggingface dataset:
Total Synthesis and Biological Activity of Neopeltolide and Analogues
2008-10-31

Abstract Combining the core structure of neopeltolide, lactone 16 a , with the oxazole‐containing side chain 23 via a Mitsunobu reaction provided the cytotoxic natural product neopeltolide ( 2 ). The side chain 23 was prepared from oxazolone 24 via the corresponding triflate. Key steps in the preparation of 23 were a Sonogashira coupling, an enamine alkylation, and a Still–Gennari Horner–Emmons reaction. By changing the Leighton reagent in the allylation step, the 11‐epimer of lactone 16 a , compound 50 was prepared. This led to 11‐ epi ‐neopeltolide 51 . The 5‐epimer of neopeltolide, compound 52 , could be obtained from the minor isomer of the Prins cyclization. Furthermore, a range of analogues with modifications in the side chain were prepared. All derivatives were checked for toxicity effects on mammalian cell cultures and inhibitory effects on NADH oxidation in submitochondrial particles of bovine heart. Modifications in the lactone part are tolerated to some degree. On the other hand, shortening the distance between the oxazole and the lactone causes a significant drop in activity. Analogue 65 with an additional double bond is equally or even more active than neopeltolide itself.
Meissner Effect in Superconducting Microtraps
2008-10-31

We report on the realization and characterization of a magnetic microtrap for ultracold atoms near a straight superconducting Nb wire with circular cross section. The trapped atoms are used to probe the magnetic field outside the superconducting wire. The Meissner effect shortens the distance between the trap and the wire, reduces the radial magnetic-field gradients, and lowers the trap depth. Measurements of the trap position reveal a complete exclusion of the magnetic field from the superconducting wire for temperatures lower than 6 K. As the temperature is further increased, the magnetic field partially penetrates the superconducting wire; hence the microtrap position is shifted towards the position expected for a normal-conducting wire.
The evolving science of atherothrombotic disease
2008-10-31

Atherosclerosis is a systemic inflammatory disease characterized by the accumulation of inflammatory cells in the intima of large arteries. The presence of platelets at the site of inflammation and endothelial injury has been known since the early 1960s. In the following years, it was generally accepted that rupture or erosion of advanced atherosclerotic lesions initiates platelet activation and aggregation on the thrombogenic surface of a disrupted atherosclerotic plaque. Thrombotic vascular occlusion is associated with ischaemic episodes in the retina, brain, heart, and other organs. While it is widely accepted that platelets play a significant role in thromboembolic events generated by atherosclerotic lesions (atherothrombosis), their involvement in the initiation of the atherosclerotic process has not been widely recognized by the scientific community. An expanding body of evidence on the role of platelets in the development of atherosclerotic lesions continues to build. Platelets bind to leukocytes and endothelial cells, and initiate the transformation of monocytes into macrophages. Additionally, platelets internalize oxidized phospholipids and promote foam cell formation, as well as recruit progenitor cells that are able to differentiate into foam or endothelial cells. In total, platelets play a key role in the initiation, development, and total extent of atherosclerotic lesions.
tert-ButylN-(4-methyl-2-pyridyl)carbamate
2008-10-31

The crystal structure of the title compound, C(11)H(16)N(2)O(2), contains two crystallographically independent mol-ecules forming dimers by pairs of inter-molecular N-H⋯N hydrogen bonds. The two mol-ecules are related by a pseudo-twofold axis. The dihedral angle between the pyridine ring and the carbamate plane differs in the two mol-ecules [12.1 (3) and 3.5 (3)°].
On the classification of isoparametric hypersurfaces with four distinct curvatures in spheres
2008-11-01

In this paper we give a new proof for the classification result in [3].We show that isoparametric hypersurfaces with four distinct principal curvatures in spheres are of Clifford type provided that the multiplicities m 1 , m 2 of the principal curvatures satisfy m 2 ≥ 2m 1 -1.This inequality is satisfied for all but five possible pairs (m 1 , m 2 ) with m 1 ≤ m 2 .Our proof implies that for (m 1 , m 2 ) = (1, 1) the Clifford system may be chosen in such a way that the associated quadratic forms vanish on the higher-dimensional of the two focal manifolds.For the remaining five possible pairs (m 1 , m 2 ) with m 1 ≤ m 2 (see [13], [1], and [15]) this stronger form of our result is incorrect: for the three pairs (3, 4), (6, 9), and (7, 8) there are examples of Clifford type such that the associated quadratic forms necessarily vanish on the lower-dimensional of the two focal manifolds, and for the two pairs (2, 2) and (4, 5) there exist homogeneous examples that are not of Clifford type; cf.[5, 4.3, 4.4].
Interaction of Monocytes with NK Cells upon Toll-Like Receptor-Induced Expression of the NKG2D Ligand MICA
2008-11-01

Abstract Reciprocal interactions between NK cells and dendritic cells have been shown to influence activation of NK cells, maturation, or lysis of dendritic cells and subsequent adaptive immune responses. However, little is known about the crosstalk between monocytes and NK cells and the receptors involved in this interaction. We report in this study that human monocytes, upon TLR triggering, up-regulate MHC class I-Related Chain (MIC) A, but not other ligands for the activating immunoreceptor NKG2D like MICB or UL-16 binding proteins 1–3. MICA expression was associated with CD80, MHC class I and MHC class II up-regulation, secretion of proinflammatory cytokines, and apoptosis inhibition, but was not accompanied by release of MIC molecules in soluble form. TLR-induced MICA on the monocyte cell surface was detected by autologous NK cells as revealed by NKG2D down-regulation. Although MICA expression did not render monocytes susceptible for NK cell cytotoxicity, LPS-treated monocytes stimulated IFN-γ production of activated NK cells which was substantially dependent on MICA-NKG2D interaction. No enhanced NK cell proliferation or cytotoxicity against third-party target cells was observed after stimulation of NK cells with LPS-activated monocytes. Our data indicate that MICA-NKG2D interaction constitutes a mechanism by which monocytes and NK cells as an early source of IFN-γ may communicate directly during an innate immune response to infections in humans.
Plant behavior upon contact with streptomycetes
2008-11-01

Plants have a variety of chemical and anatomical defences, whose strengths depend on biotic and environmental influences. We show here that root inoculation with belowground bacteria, filamentous gram-positive streptomycetes, can induce plant defence responses. Such induced plant responses can occur belowground in the roots, but also aboveground, in the leaves, and include priming (sensitizing) like characters. Streptomycetes have also evolved mechanisms to facilitate plant root symbioses, mycorrhiza and root nodulation. By promoting fungal growth and by decreasing plant defence responses, these bacteria promote mycorrhiza formation. This minireview covers our current knowledge on the complex interactions that take place between streptomycetes, plants and rhizosphere microbes.
Essential differences in ligand presentation and T cell epitope recognition among HLA molecules of the HLA‐B44 supertype
2008-11-01

Abstract Human leukocyte antigens (HLA) have long been grouped into supertypes to facilitate peptide‐based immunotherapy. Analysis of several hundreds of peptides presented by all nine antigens of the HLA‐B44 supertype (HLA‐B * 18, B * 37, B * 40, B * 41, B * 44, B * 45, B * 47, B * 49 and B * 50) revealed unique peptide motifs for each of them. Taking all supertype members into consideration only 25 out of 670 natural ligands were found on more than one HLA molecule. Further direct comparisons by two mass spectrometric methods – isotope labeling as well as a label‐free approach – consistently demonstrated only minute overlaps of below 3% between the ligandomes of different HLA antigens. In addition, T cell reactions of healthy donors against immunodominant HLA‐B * 44 and HLA‐B * 40 epitopes from EBV lacked promiscuous T‐cell recognition within the HLA‐B44 supertype. Taken together, these results challenge the common paradigm of broadly presented epitopes within this supertype.
Long-Term Immunity against Actual Poxviral HLA Ligands as Identified by Differential Stable Isotope Labeling
2008-11-01

Abstract Viral peptides are presented by HLA class I on infected cells to activate CD8+ T cells. Several immunogenic peptides have been identified indirectly by epitope prediction and screening of T cell responses to poxviral vectors, including modified vaccinia virus Ankara (MVA) currently being tested as recombinant or smallpox vaccines. However, for the development of optimal vaccination and immunomonitoring strategies, it is essential to characterize the actual viral HLA ligand repertoire of infected cells. We used an innovative approach to identify naturally processed MVA HLA ligands by differential HPLC-coupled mass spectrometry. We describe 12 viral peptides presented by HLA-A*0201 and 3 by HLA-B*0702. All HLA-A*0201 ligands participated in the memory response of MVA-immune donors, and several were immunogenic in Dryvax vaccinees. Eight epitopes were novel. Viral HLA ligand presentation and viral protein abundance did not correlate. All ligands were expressed early during the viral life cycle, and a pool of three of these mediated stronger protection against a lethal challenge in mice as compared with late epitopes. This highlights the reliability of the comparative mass spectrometry-based technique to identify relevant viral CD8+ T cell epitopes for optimizing the monitoring of protective immune responses and the development of effective peptide-based vaccines.
BK channels in Purkinje cell plasma membranes are concentrated in plasmerosomes at sites of hypolemmal cisternae
2008-11-01

Calcium-activated potassium channels have been shown to be critically involved in neuronal function but an elucidation of their detailed roles awaits identification of the subcellular domains and microdomains where they are located. This study was undertaken to unravel the precise subcellular distribution of the big-conductance calcium-activated potassium channels (called BK, KCa1.1 or Slo1) in the somato-dendritic compartment of cerebellar Purkinje cells by means of postembedding immunogold cytochemistry and SDS-digested freeze-fracture replica labeling (SDS-FRL). We found BK channels to be unevenly distributed over the Purkinje cell plasma membrane and localized to specific subcellular domains. At distal dendritic compartments, BK channels were scattered over the plasma membrane of shafts and spines, but absent from postsynaptic densities. At the soma and proximal dendrites, BK channels formed two distinct pools. One pool was scattered over the plasma membrane, the other pool was clustered in plasma membrane domains overlying subsurface membrane cisterns, also called hypolemmal cisternae. These subcompartments of the endoplasmic reticulum likely represent calciosomes that unload and refill Ca2+ independently. Purkinje cell subsurface cisterns are enriched in inositol 1,4,5-triphosphate receptors that mediate the effects of several neurotransmitters, hormones and growth factors by releasing Ca2+ into the cytosol, generating local Ca2+ sparks. Such increases in cytosolic [Ca2+] may be sufficient for BK channel activation. Clustered BK channels in the plasma membrane may thus participate in building a functional unit (plasmerosome) with the underlying calciosome that contributes significantly to local signaling in Purkinje cells.
Chronic administration of rotenone induces Parkinsonian symptoms and increases levels of nitric oxide in rat brain
2008-11-01

Background Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases. A reduction of complex I activity has been demonstrated in mitochondria of PD patients. Recently, it was shown that chronic subcutaneous exposure to low doses of rotenone (an inhibitor of mitochondrial NADH dehydrogenase and a commonly used pesticide) caused highly selective nigrostriatal dopaminergic lesions. However, while the behavioural effects of rotenone administration are well characterised, the mechanisms underlying rotenone action are unclear. Recent studies are regarding nitric oxide (NO) as universal neuronal messenger in the pathophysiology of neurodegenerative diseases. The aim of this work is to study mechanisms underlying oxidative damage of the various brain areas of rats produced by rotenone and to investigate a possible role of NO and lipid peroxidation (LPO) processes during chronic rotenone administration.
Constructing a Valence Lexicon for a Treebank of German
2008-11-01

"Treebanks allow for the creation of a valence lexicon per side effect. The TüBa-D/Z&#13;\\nvalence lexicon has been created in lockstep with the development of the TüBa-&#13;\\nD/Z treebank as such. For each verb encountered in the treebank, the annotators&#13;\\ncreated a lexical entry that records the valence frames of the verbs contained in&#13;\\nthe sentence, unless they are already contained in the valence lexicon as result of&#13;\\nprevious annotation. The TüBa-D/Z valence lexicon currently contains a total of&#13;\\n8013 frames for 4896 distinct verb lemmas. Since treebank annotation is still ongoing,&#13;\\nthe lexicon will continue to grow.&#13;\\nSuch a lexicon has utility in its own right as a resource for lexicalized parsing&#13;\\nand a variety of NLP applications. At the same time, the lexicon can serve as a&#13;\\nsource for aiding consistency of annotation and automatic detection of annotation&#13;\\nerrors"
Successful Diagnosis and Treatment 50 Years After Exposure: Is Mucocutaneous Leishmaniasis Still a Neglected Differential Diagnosis?
2008-11-01

We present a case of a long-term history of imported mucocutaneous leishmaniasis, illustrating the importance of this differential diagnosis even decades after exposure. Diagnostic pitfalls and the role of primary subspecies differentiation are demonstrated. Chemotherapy avoiding antimonials was successful and remarkably well tolerated by an elderly patient.
MonaSearch - A Tool for Querying Linguistic Treebanks
2008-11-01

MonaSearch is a new powerful query tool for linguistic treebanks. The&#13;\\nquery language of MonaSearch is monadic second-order logic, an extension&#13;\\nof first-order logic capable of expressing probably all linguistically interesting&#13;\\nqueries. In order to process queries efficiently, they are compiled into tree&#13;\\nautomata. A treebank is queried by checking whether the automaton representing&#13;\\nthe query accepts the tree, for each tree. Experiments show that even&#13;\\ncomplex queries can be executed very efficiently. The tree automaton toolkit&#13;\\nMONA is used for the computation of the automata.
Catalyst patterning for carbon nanotube growth on elevating posts by self-aligned double-layer electron beam lithography
2008-11-01

For gas-flow aligned growth of carbon nanotubes (CNTs), it is important to minimize interaction of the growing CNTs with the substrate. The authors present a method to fabricate thin catalyst films on top of protruding hydrogen silsesquioxane (HSQ) patterns. Self-alignment of the catalyst film with the HSQ pattern is achieved by exposing two layers of resist, polymethyl methacrylate (PMMA) on top of HSQ, simultaneously. By selecting appropriate development parameters for PMMA and HSQ, a common exposure dose can be applied. After a standard lift-off process HSQ is developed and CNTs are grown on the protruding HSQ patterns resulting in gas-flow aligned CNTs that can be further processed, e.g., for the fabrication of CNT based transistors.
Managing the β-cell with GLP-1 in type 2 diabetes
2008-11-01

The clinical course of type 2 diabetes mellitus is characterised by a progressive decline in β -cell mass. The changing β-cell mass reflects a shifting balance between β-cell neogenesis, islet neogenesis and β-cell apoptosis. In persons with diabetes, administration of exogenous glucagon-like peptide-1 (GLP-1) improves glucose sensitivity and insulin synthesis and may help increase β cell mass. As the effects of GLP-1 on the β cell are becoming better understood at both the molecular and cellular levels, it has become possible to develop therapies with the potential to harness and sustain the positive effects of endogenous GLP-1 in patients with type 2 diabetes. Data from in vitro, preclinical and phase II studies show promising results with GLP-1 analogues in improving β-cell function in patients with type 2 diabetes. For example, in vitro models have shown the GLP-1 analogue liraglutide inhibits β-cell apoptosis in isolated neonatal rat islets. In vitro, animal models demonstrate increasing β-cell mass with liraglutide administration. Results from a recently completed phase II clinical trial with liraglutide in patients with type 2 diabetes demonstrate that daily treatment markedly improves β -cell function as shown by an increased first-phase insulin response and secretory capacity and a decreased proinsulin:insulin ratio. Now, phase III trials continue to bear out the potential for liraglutide for treatment of patients with type 2 diabetes.Br J Diabetes Vasc Dis 2008;8 (Suppl 2): S19-S25
RIM modulates CaV1.3 Ca2+ channels
2008-11-01

Calcium channel β subunits (CaVβs) are essential cytoplasmic components of voltage-gated calcium channels (VGCCs) affecting their gating and targeting. CaVβs bind with high affinity to the cytoplasmic loop between transmembrane segments I and II of the α1 subunit (loop-I-II). To identify new proteins that modulate VGCCs by interaction with CaVβs we performed a yeast two-hybrid screen using CaVβ2a as bait. Screening of a human fetal brain cDNA library identified a C-terminal fragment of RIM1α (Rab3-interacting molecule) which contains a highly conserved C2B domain as potential interaction partner. To proof the interaction between RIM and CaVβs we developed a protein targeting assay in tsA-201 cells heterologously expressing the loop-I-II of CaV1.3 channels with diverse CaVβ subunits. The CaV1.3-loop-I-II was transported to the plasma membrane and co-targeted all CaVβ subunits indicating that the CaV1.3-loop-I-II and the CaVβ subunits formed a functional complex. The C-terminal fragment of RIM1α or the full-length form of RIM2β exhibited a cytoplasmic distribution but when co-expressed with CaVβs in presence of the CaV1.3-loop-I-II both were co-localized at the plasma membrane. Using qualitative RT-PCR analysis we detected various RIM isoforms in the total organ of Corti and RIM2α in cochlea inner hair cells (IHCs) at an early developmental stage, before the onset of hearing. As RIM is a presynaptic active zone protein involved in Ca2+-induced neurotransmitter release, we asked the question whether the association of RIM with CaV1.3 could account for the slow CaV1.3 current inactivation seen in IHCs. In whole-cell patch-clamp analysis of tsA-201 cells using 15 mM Ca2+ as charge carrier the C2B domain containing fragments of RIM1α and RIM2α caused a significant depolarizing shift of the activation-curve of CaV1.3 (7–12 mV) and slowed the inactivation of both Ca2+ and Ba2+ currents (p < 0.05) albeit to a lesser extent as found in native IHCs. To investigate if a slowly inactivating CaV1.3 spliceform (1b) could contribute to this effect we examined its expression with RT-PCR analysis. However, we did not detect CaV1.3(1b) transcripts in the total organ of Corti at the same developmental stage as we found RIM. Taken together these data showed that indeed RIM modulated CaV1.3 Ca2+ channels. However, we assume that a mixture of diverse proteins and/or CaV1.3 splice variants probably accounts for the slow current inactivation of these channels in native IHCs.
Neuroethik
2008-11-01

Abstract Ethical questions with regard to modern neurosciences have significant relevance because the human brain provides the organic basis for central aspects of our self-concept. Neuroethics identifies and reflects the ethical questions raised by modern neurosciences. Here we deal with ethical questions in the contexts of brain imaging techniques and several interventions into the human brain. Besides the central question how to preserve personal identity and higher cognitive functions we address specific ethical aspects of neurotechnology and neuroprosthetics as well as the questions relevant in the context of neuroenhancement
Free and constrained symplectic integrators for numerical general relativity
2008-11-03

We consider symplectic time integrators in numerical General Relativity and discuss both free and constrained evolution schemes. For free evolution of ADM-like equations we propose the use of the Stoermer-Verlet method, a standard symplectic integrator which here is explicit in the computationally expensive curvature terms. For the constrained evolution we give a formulation of the evolution equations that enforces the momentum constraints in a holonomically constrained Hamiltonian system and turns the Hamilton constraint function from a weak to a strong invariant of the system. This formulation permits the use of the constraint-preserving symplectic RATTLE integrator, a constrained version of the Stoermer-Verlet method. The behavior of the methods is illustrated on two effectively 1+1-dimensional versions of Einstein's equations, that allow to investigate a perturbed Minkowski problem and the Schwarzschild space-time. We compare symplectic and non-symplectic integrators for free evolution, showing very different numerical behavior for nearly-conserved quantities in the perturbed Minkowski problem. Further we compare free and constrained evolution, demonstrating in our examples that enforcing the momentum constraints can turn an unstable free evolution into a stable constrained evolution. This is demonstrated in the stabilization of a perturbed Minkowski problem with Dirac gauge, and in the suppression of the propagation of boundary instabilities into the interior of the domain in Schwarzschild space-time.
Simulating the Outcrop: Surface To Subsurface Integration of a Carbonate Reservoir, Khuff Formation, Oman
2008-11-03

Abstract Careful gathering and analysis of outcrop analogue data is a valuable data source for enhancing the understanding of analogue hydrocarbon reservoirs. However, information from outcrops is commonly limited to static descriptions, i.e. reservoir body dimension and geometry. Figure 1 Permo-Triassic Section exposed at Jebel Al Akhdar. Visible is a large-scale layer cake-type carbonate ramp made up of thin but laterally extensive units. The formation has been subdivided into six composite sequences (KS1 shown in red to KS6 shown in dark blue). The main facies types are: 1 graded peloidal oolitic packstones to grainstones, 2 mottled and rooted mudstones, 3 graded oolitic grainstones, 4 cross-bedded oolitic grainstones.