julilili42/papers huggingface dataset:
Usher syndrome type 1 due to missense mutations on bothCDH23 alleles: investigation of mRNA splicing
2008-01-01

Usher syndrome (USH) is an autosomal recessive condition characterized by sensorineural hearing loss, vestibular dysfunction, and visual impairment due to retinitis pigmentosa. Truncating mutations in the cadherin-23 gene (CDH23) result in Usher syndrome type 1D (USH1D), whereas missense mutations affecting strongly conserved motifs of the CDH23 protein cause non-syndromic deafness (DFNB12). Four missense mutations constitute an exception from this genotype-phenotype correlation: they have been described in USH1 patients in homozygous state. Using a minigene assay, we have investigated these changes (c.1450G>C, p.A484P; c.3625A>G, p.T1209A; c.4520G>A, p.R1507Q; and c.5237G>A, p.R1746Q) for a possible impact on mRNA splicing which could explain the syndromic phenotype. While in silico analysis suggested impairment of splicing in all four cases, we found aberrant splicing for only one mutation, p.R1746Q. However, splicing was normal in case of p.A484P, p.T1209A and p.R1507Q. These three latter CDH23 missense mutations could interfere with functions of both, the auditory and the visual system. Alternatively, they could represent rare non-pathogenic polymorphisms.
Identification of osteopontin as the most consistently over-expressed gene in intrahepatic cholangiocarcinoma: Detection by oligonucleotide microarray and real-time PCR analysis
2008-01-01

A highly specific gene expression profile for intrahepatic CCC was identified, allowing for its fast and reproducible discrimination against non-malignant liver tissue and other liver masses. The most overexpressed gene in intrahepatic CCC was the gene encoding osteopontin. These data may lead to a better understanding of human cholangiocarcinogenesis.
RIL &#x2014; reliable RFID based indoor localization for pedestrians
2008-01-01

Various approaches based on different wireless technologies have been proposed for indoor localization; however RFID technology remained the key focus of research in recent years compared to other technologies available on the market. RFID localization solutions are based either on tag detection count or signal attenuation, yet their reliability are not consistent. In this paper, we propose a novel approach that guarantees a reliable solution for indoor localization. Our localization algorithm confines the userpsilas location by a combination of tag detection and RSSI measurement. The results are refined by the use of filtering algorithm.
Authority in the Global Political Economy
2008-01-01

Editors' Preface Introduction: Changing Patterns of Authority V.Rittberger, M.Nettesheim, C.Huckel & T.Goebel PART ONE: NEW INSTITUTIONS FOR GLOBAL GOVERNANCE Inclusive Global Institutions for a Global Political Economy V.Rittberger, C.Huckel, L.Rieth & M.Zimmer The WTO Constitution, Judicial Power and Changing Patterns of Authority J.L.Dunoff PART TWO: PROVIDING AND MANAGING GLOBAL PUBLIC GOODS Providing (Contested) Global Public Goods I.Kaul Global Public Goods - The Governance Dimension P.Stoll PART THREE: CIVIL SOCIETY AND GLOBAL GOVERNANCE International NGOs: Scale, Expressions and Governance H.K.Anheier & N.S.Themudo The Emerging Global Civil Society: Achievements and Prospects W.Benedek PART FOUR: BUSINESS IN GLOBAL GOVERNANCE Problematizing Corporate Social Responsibility under Conditions of Late Capitalism and Postmodernity A.C.Cutler MNCs and the International Community: Conflict, Conflict Prevention and the Privatization of Diplomacy V.Haufler PART FIVE: REGULATION IN GLOBAL GOVERNANCE Rearticulating Regulatory Approaches: Private-Public Authority and Corporate Social Responsibility P.Utting The Two Level Logic of Non-State Market Driven Global Governance S.Bernstein & B.Cashore Conclusion: Authority Beside and Beyond the State V.Rittberger, M.Nettesheim, C.Huckel & T.Goebel
Adrenergic Regulation of cAMP/Protein Kinase A Pathway in Corneal Epithelium and Endothelium
2008-01-01

&lt;i&gt;Purpose:&lt;/i&gt; The G-protein-coupled receptor/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway is one of the most common and versatile signal pathways in eukaryotic cells. The aim of this study was to characterize subtypes of adrenergic G-protein-coupled receptors and their influence on cAMP concentration and PKA activity in bovine corneal epithelial and endothelial cells. &lt;i&gt;Procedures:&lt;/i&gt; Adrenergic receptors and PKA were studied using polyclonal antibodies. cAMP concentration was determined with an enzyme immunoassay, and PKA activity was estimated by the kinases consumption of adenosine triphosphate. &lt;i&gt;Results:&lt;/i&gt; In bovine corneal epithelial and endothelial cells, immunocytochemistry and Western blot were positive for α&lt;sub&gt;1&lt;/sub&gt;-, α&lt;sub&gt;2A&lt;/sub&gt;-, β&lt;sub&gt;1&lt;/sub&gt;- and β&lt;sub&gt;2&lt;/sub&gt;-adrenergic receptors. Stimulation of corneal epithelial and endothelial β-adrenoceptors with isoprenaline led to a dose-dependent increase in cAMP concentration and activation of PKA. Stimulation of corneal α&lt;sub&gt;2A&lt;/sub&gt;-adrenoceptors with brimonidine resulted in a dose-dependent decrease in cAMP concentration and the inhibition of PKA activity. &lt;i&gt;Conclusions:&lt;/i&gt; In corneal epithelial and endothelial cells, β-adrenergic stimulation leads to activation of PKA via stimulation of adenylyl cyclase, and α&lt;sub&gt;2A&lt;/sub&gt;-adrenoceptor stimulation inhibits PKA activity via inhibition of adenylyl cyclase. Stimulation and inhibition of the corneal cAMP-PKA pathway may play a role in important corneal functions such as wound healing or homeostasis. Long-term therapy with α&lt;sub&gt;2A&lt;/sub&gt;-agonists or β-antagonists may influence these functions in a currently unknown way.
Fixed-Parameter Algorithms in Phylogenetics
2008-01-01

This chapter surveys the use of fixed-parameter algorithms in phylogenetics. A central computational problem in this field is the construction of a likely phylogeny (genealogical tree) for a set of species based on observed differences in the phenotype, differences in the genotype, or given partial phylogenies. Ideally, one would like to construct so-called perfect phylogenies, which arise from an elementary evolutionary model, but in practice one must often be content with phylogenies whose "distance from perfection" is as small as possible. The computation of phylogenies also has applications in seemingly unrelated areas such as genomic sequencing and finding and understanding genes. The numerous computational problems arising in phylogenetics are often NP-complete, but for many natural parametrizations they can be solved using fixed-parameter algorithms.
Coreference systems based on kernels methods
2008-01-01

Various types of structural information - e.g., about the type of constructions in which binding constraints apply, or about the structure of names - play a central role in coreference resolution, often in combination with lexical information (as in expletive detection). Kernel functions appear to be a promising candidate to capture structure-sensitive similarities and complex feature combinations, but care is required to ensure they are exploited in the best possible fashion. In this paper we propose kernel functions for three subtasks of coreference resolution - binding constraint detection, expletive identification, and aliasing - together with an architecture to integrate them within the standard framework for coreference resolution.
Selective inhibition of the platelet phosphoinositide 3-kinase p110β as promising new strategy for platelet protection during extracorporeal circulation
2008-01-01

Summary Extracorporeal circulation (ECC) is used in cardiac surgery for cardiopulmonary bypass as well as in ventricular assist devices and for extracorporeal membrane oxygenation. Blood contact with the artificial surface and shear stress of ECC activates platelets and leukocytes resulting in a coagulopathy and proinflammatory events. Blockers of the platelet glycoprotein (GP) IIb/IIIa (CD41/CD61) can protect platelet function during ECC, a phenomenon called “platelet anaesthesia”, but may be involved in post-ECC bleeding. We hypothesized that the new selective phosphoinositide 3-kinase p110β inhibitor TGX-221 that inhibits shear-induced platelet activation without prolonging the bleeding time in vivo may also protect platelet function during ECC. Heparinized blood of healthy volunteers (n=6) was treated in vitro with either the GP IIb/IIIa blocker tirofiban, TGX-221 or as control and circulated in an ECC moand after 30 minutes circulation CD41 expression on the ECCtubing as measure for platelet-ECC binding and generation of the platelet activation marker β-thromboglobulin were determined using ELISA. Platelet aggregation and platelet-granulocyte binding were analysed in flow cytometry. After log-transforming the data statistical evaluation was performed using multifactor ANOVA in combination with Tukey’s HSD test (global alpha = 5%).Tirofiban and TGX-221 inhibited platelet-ECC interaction, platelet aggregation and platelet-granulocyte binding. Tirofiban also inhibited ECC-induced β-thromboglobulin release.The observed inhibition of platelet-ECC interaction and platelet activation by tirofiban contributes to explain the mechanism of“platelet anaesthesia”.TGX-221 represents a promising alternative to GP IIb/IIIa blockade and should be further investigated for use during ECC in vivo.
Validation criteria for nucleic acid amplification techniques for bacterial infections
2008-01-01

Nucleic acid techniques (NATs), such as species-specific and universal polymerase chain reactions (PCRs), are finding ever wider use in the diagnosis of bacterial infection. However, although universal PCR assays, in particular, approach a type of modern Petri dish, they have a number of limitations which restrict their applicability. The sensitivity of universal PCR is lower than that of many species-specific PCRs, and the contamination of samples and PCR reagents with irrelevant DNA from various sources remains a problem. Thus, NATs in general and universal PCR assays in particular require careful validation to be of value for the diagnosis of infection. Validation includes sampling, DNA extraction/isolation, template amplification and visualisation of the results. Furthermore, it implies the establishment of measures of asepsis, the inclusion of positive and negative controls, techniques to optimise the release of DNA from bacterial cells, adequate repetition of the amplification reaction, and routine testing of reagent negative and inhibition controls. Finally, it entails the comparison of results obtained by NATs with those obtained by conventional microbiological methods and matching with clinical evidence of infection. Validation of NATs in clinical diagnosis remains an ongoing challenge. Because of these limitations, NATs can only serve as adjunct tools for the diagnosis of infection in selected cases; they cannot replace conventional culturing techniques.
IGF-1 Protects Against Dexamethasone-Induced Cell Death in Insulin Secreting INS-1 Cells Independent of AKT/PKB Phosphorylation
2008-01-01

Appropriate insulin secretion depends on beta-cell mass that is determined by the balance between cell proliferation and death. IGF-1 stimulates proliferation and protects against apoptosis. In contrast, glucocorticoids promote cell death. In this study we examined molecular interactions of the glucocorticoid dexamethasone (dexa) with IGF-1 signalling pathways in insulin secreting INS-1 cells. IGF-1 (50 ng/ml) increased the growth rate and stimulated BrdU incorporation, while dexa (100 nmol/l) inhibited cell growth, BrdU incorporation and induced apoptosis. Dexa-induced cell death was partially antagonized by IGF-1. This protection was further increased by LY294002 (10 micromol/l), an inhibitor of PI3 kinase. In contrast, MAP kinase inhibitor PD98059 (10 micromol/l) significantly reduced the protective effect of IGF-1. The analysis of signalling pathways by Western blotting revealed that dexa increased IRS-2 protein abundance while the expression of PI3K, PKB and ERK remained unchanged. Despite increased IRS-2 protein,IRS-2 tyrosine phosphorylation stimulated by IGF-1 was inhibited by dexa. Dexa treatment reduced basal PKB phosphorylation. However, IGF-1-mediated stimulation of PKB phosphorylation was not affected by dexa, but ERK phosphorylation was reduced. LY294002 restored IGF-1-induced ERK phosphorylation. These data suggest that dexa induces apoptosis in INS-1 cells by inhibiting phosphorylation of IRS-2, PKB and ERK. IGF-1 counteracts dexa-mediated apoptosis in the presence of reduced PKB but increased ERK phosphorylation.
Changes in acral blood flux under local application of ropivacaine and lidocaine with and without an adrenaline additive: a double-blind, randomized, placebo-controlled study.
2008-01-01

Vascular effects of local anesthetics are especially important in dermatological surgery. In particular, adequate perfusion must be ensured in order to offset surgical manipulations during surgical interventions at the acra. However, the use of adrenaline additives appears fraught with problems when anesthesia affects the terminal vascular system, particularly during interventions at the fingers, toes, penis, outer ears, and tip of the nose. We studied skin blood flux at the fingerpads via laser Doppler flowmetry over the course of 24 hours in a prospective, double-blind, randomized, placebo-controlled study with 20 vascularly healthy test persons following Oberst's-method anesthetic blocks. In each case, 6 ml ropivacaine (7.5 mg/ml) (A), lidocaine 1% without an additive (B), and lidocaine 1% with an adrenaline additive (1:200,000) (C) was used respectively as a verum. Isotonic saline solution was injected as a placebo (D). Measurements were carried out with the aid of a computer simultaneously at D II and D IV on both hands. Administration of (A) led to increased blood flux (+155.2%); of (B) initially to a decrease of 27%; of (C) to a reduction of 55% which was reversible after 40 minutes and of (D) to no change.(A) resulted in sustained vasodilatation which was still demonstrable after 24 h. (B) had notably less vasodilative effect, although comparison with (D) clearly showed that (B) is indeed vasodilative. (C) resulted in only a passing decrease in perfusion; this was no longer measurable when checked after 6 and 24 h. This transient inadequacy of blood flux also appeared after administration of (D). These tests show that adrenaline additive in local anesthesia does not decrease blood flow more than 55% for a period of 16 min. Following these results an adrenaline additive can be safely used for anesthetic blocks at the acra in healthy persons.
Lorenzen’s operative justification of intuitionistic logic
2008-01-01

With his Introduction to Operative Logic and Mathematics1, which first appeared in 1955, Paul Lorenzen became an exponent of an approach to the foundations of logic and mathematics, which is both formalistic and intuitionistic in spirit. Formalistic because its basis is the purely syntactical handling of symbols—or 'figures', as Lorenzen preferred to say —, and intuitionistic because the insight into the validity of admissibility statements justifies the laws of logic. It is also intuitionistic with respect to its result, as Heyting's formalism of intuitionistic logic is legitimatised this way. Along with taking formal calculi as its basis, the notion of an inductive definition becomes fundamental. Together with a theory of abstraction and the idea of transfinitely interating inductive definitions, Lorenzen devised a novel foundation for mathematics, many aspects of which still deserve attention. When he wrote his Operative Logic, neither a full-fledged theory of inductive definitions nor a proof-theoretic semantics for logical constants was available. A decade later, Lorenzen's inversion principle was used and extended by Prawitz (Prawitz 1965) in his theory of natural deduction, and in the 1970s, the idea of inversion was used for a logical semantics in terms of proofs by Dummett, Martin-Löf, Prawitz and others. Prawitz and others. Another aspect which makes Lorenzen' theory interesting from a modern point of view, is that in his protologic he anticipated certain views of rule-based reasoning and free equality which much later became central to the theory of resolution and logic programming.
η1 and η2 Coordination of 1-amino-closo-dodecaborate
2008-01-01

The reaction of the sodium salt of 1-amino-closo-dodecaborate [Na]2[NH2-B12H11] ([Na]2[1]) with [Au(PPh3)Cl] and [Ni(THF)2(Br)2] led to eta 1(N) coordination of 1in [Na][Au(PPh3)(NH2-B12H11)] (2) and [Na]6[Ni(NH2-B12H11)4] (3), respectively. Furthermore, eta 2(N,BH) coordination of was found in [MePPh3][Rh(PPh3)2(NH2-B12H11)] (4), which was synthesized by the reaction of [MePPh3][Na][1] with [Rh(PPh3)3Cl]. All compounds were characterized by single crystal X-ray diffraction and heteronuclear NMR spectroscopy.
Bladder Cancer: Chemoprevention, complementary approaches and budgetary considerations
2008-01-01

Bladder cancer results from complex and only partially understood host-environmental interactions. Tobacco smoking is the greatest risk factor for bladder cancer, but the actual risk to an individual reflects not only the amount of exposure to the carcinogens in tobacco smoke but also host susceptibility to these carcinogens and possibly other factors. Lifestyle may have a significant effect on the incidence of this disease. The forms of chemoprevention and their relevance to bladder cancer, the impact of lifestyle and complementary medicine, and the costs of diagnosing and treating bladder cancer are reviewed to provide a base for advances in decreasing the incidence, recurrence and costs of this disease.
A Young Woman with Recurrent Vesicles on the Lower Lip: Fixed Drug Eruption Mimicking Herpes Simplex
2008-01-01

A 23-year-old woman presented with recurrent herpetiform vesicles of the lower lip, but all diagnostic measures for herpes virus infection including herpes viridae specific PCR were negative. Medical history revealed that she also had chronic recurrent vulvovaginal candidiasis, which had been treated with various regimes, including repetitive applications of fluconazole. Consequently, fluconazole-induced fixed drug eruption was suspected, but skin tests performed with fluconazole remained with-out response. Consecutive repeated oral provocation tests with fluconazole were carried out and resulted in the development of burning herpetiform vesicles of the lower lip. Histopathology revealed a subepidermal and superficial perivascular infiltrate, basal vacuolated and apoptotic keratinocytes, intra-epidermal lymphocytes and intra-epidermal multilocular vesicles. Together with the clinical history and picture, fluconazole-induced fixed drug eruption mimicking labial herpes simplex virus infection was diagnosed. Oral provocation tests with an alternative systemic antifungal treatment, itraconazole, were well tolerated, systemic therapy with itraconazole was initiated, and no further labial vesicles developed.
Thermal evolution Cooling of the Žiar Mountains basement (Inner Western Carpathians, Slovakia) constrained by fission track data
2008-01-01

Thermal evolution of the Žiar Mts was studied using zircon and apatite fission track (ZFT and AFT) thermochronology applied to basement and sedimentary rocks. Basement samples from the Tatric Unit of the Inner Western Carpathians (IWC) yielded cooling ZFT ages in the range from 109 ± 5.9 to 92.1 ± 5.3 Ma and apparent AFT ages between 33.7 ± 2.7 and 24.4 ± 1.7 Ma. Paleogene sediments of the Central Carpathian Paleogene Basin (CCPB) yielded apparent AFT ages of 73.2 ± 2.7 and 49.6 ± 1.8 Ma. ZFT data show that during early Late Cretaceous thrusting the crystalline basement was buried by a nappe pile to crustal depths with temperatures between 210 and 310 °C, where the crystalline core was metamorphosed at anchizonal conditions. AFT data revealed a complex thermal evolution, implying that after nappe stacking and metamorphism the basement was exhumed to the surface and that it was buried beneath a thick pile of sediments of the CCPB. The CCPB was inverted and the basement finally exhumed in the Late Oligocene to Early Miocene. The AFT system in the basement and CCPB samples record also a distinct, Middle Miocene thermal event, related to the increased heat flow induced by upwelling of hot mantle material and related volcanic activity. Our data support the hypothesis that the study area was part of a large CCPB basin and contradict the widely accepted assumption that the Variscan crystalline core of the Žiar Mts lacks an Alpine metamorphic overprint.
The clinico-surgico-pathological spectrum of myxopapillary ependymomas report of four unusal cases and review of the literature
2008-01-01

According to the WHO grading system, myxopapillary ependymomas are assigned to WHO Grade I. However, the clinico-pathological spectrum might be very heterogenous. Herein, we report 4 cases exhibiting lumbar tumor masses, 1 causing muscular atrophy over a 30-year period, 3 displaying clinical history of persisting lumbar pain for only several weeks. All tumors were crooked with dura and spinal roots resulting in incomplete resection in three cases. On histological examination, two tumors were almost acellular and showed polycyclic hyaline and fibrotic extracellular matrix leading to differential diagnoses of chordoma, meningioma, fibrolipoma and ependymoma. Finally, together with the immunohistochemical investigations, electron microscopy led to the diagnosis of myxopapillary ependymoma, WHO Grade I, with massive degenerative changes. The other 2 cases presented with the typical neuropathology of myxopapillary ependymomas but showed local recurrence within 1 and 13 years throughout the whole neuraxis, and in 1 case additional metastases of the 3rd ventricle. Although the morphological feature of these myxopapillary ependymomas was benign, the presented cases showed that the biological behavior of myxopapillary tumors might differ greatly and that these tumors present a serious operative and diagnostic challenge. Myxopapillary ependymomas occur most often in the lumbosacral region. Due to the anatomic complexity of the cauda equina, a complete resection can be technically challenging in this region. However, a gross total resection at the primary surgery is the most predictive factor for the outcome.
Novel Insights into the Structural Basis of pH-Sensitivity in Inward Rectifier K<sup>&plus;</sup> Channels Kir2.3
2008-01-01

The Kir2 channels belong to a family of potassium selective channels with characteristic strong inward rectification. Heteromeric assemblies of Kir2.1, Kir2.2 and Kir2.3 channels underly membrane potential stabilizing currents in ventricular myocytes, neurons and skeletal muscle. Kir2 channels differ substantially in their sensitivity to extracellular pH. The extracellular histidine Kir2.3(H117) contributes to the pH dependence of K-channels containing Kir2.3. Here, we study the possibility of intramolecular interactions of the residue Kir2.3(H117) with conserved cysteines in close proximity to the selectivity filter. We engineered a cobalt coordination site and reduction/oxidation sensitivity in Kir2.3 by introduction of a cysteine into the putatively hydrogen bonding residue (Kir2.3(H117C)) confirming that this residue is in proximity to Kir2.3(C141). Using SCAM we determined the location of the Kir2.3(H117) in the outer pore mouth and incorporated these data into a 3D model. We conclude that formation of a hydrogen bond at low pH may stabilize the outer pore domain to favour the selectivity filter in a slightly distorted conformation thus reducing ion permeation. The data provide molecular insight into the unique pH regulation of inward rectifier channels.