julilili42/papers huggingface dataset:
Deranged Kv channel regulation in fibroblasts from mice lacking the serum and glucocorticoid inducible kinase SGK1
2004-12-16

Abstract Coexpression of the serum and glucocorticoid inducible kinase 1 (SGK1) up‐regulates Kv channel activity in Xenopus oocytes and human embryonic kidney cells. To investigate the physiological impact of SGK1 dependent Kv channel regulation, we recorded whole‐cell currents in lung fibroblasts from SGK1 knockout mice (sgk1−/−) and wild‐type littermates (sgk1+/+). Serum‐grown mouse lung fibroblasts (MLF) from both genotypes exhibited voltage‐gated outwardly rectifying K + ‐currents with time‐dependent activation (τ act ∼3 msec), slow inactivation (τ inact ∼700 msec), use‐dependent inactivation, and (partial) inhibition by K + channel blockers TEA, 4‐AP, and margatoxin. In serum grown MLF peak Kv current density at +100 mV was significantly lower in sgk1−/− (14 ± 2 pA/pF, n = 13) than in sgk1+/+ (31 ± 4 pA/pF, n = 16). PCR amplification of different Kv1 and Kv3 subunits from mouse fibroblasts demonstrated the expression of Kv1.1‐1.7, Kv3.1, and Kv3.3 mRNA in both sgk1+/+ and sgk1−/− cells. Upon serum deprivation Kv currents almost disappeared in sgk1+/+ (4 ± 1 pA/pF, n = 11) but not in sgk1−/− (10 ± 1 pA/pF, n = 6) MLF. Accordingly, following serum deprivation Kv current density was significantly lower in sgk1+/+ than in sgk1−/−. Stimulation of serum‐depleted cells with dexamethasone (dex) (1 μM, 1 day), IGF‐1 (6.7 μM, 4–6 h) or both, significantly activated Kv currents in sgk1+/+ but not in sgk1−/− MLF. In the presence of both, dex and IGF‐1, the Kv current density was significantly larger in sgk1+/+ (27 ± 3 pA/pF, n = 12) than in sgk1−/− (13 ± 3 pA/pF, n = 10) cells. Similar to MLF, Kv currents were significantly higher in sgk1+/+ mouse tail fibroblasts (MTF). In sgk1+/+ but not sgk1−/− MTF the Kv currents were inhibited upon serum deprivation and reincreased after stimulation of serum deprived MTF with dex (1 μM, 1 day) and afterwards with IGF‐1 (6.7 μM, 4–6 h). According to Fura‐2‐fluorescence capacitative Ca 2+ entry was lower in sgk1−/− MTF compared to sgk1+/+ MTF. Upon serum deprivation capacitative Ca 2+ entry decreased significantly in sgk1+/+ but not in sgk1−/− MTF. Stimulation of depleted cells with dex (1 μM, 1 day) and afterwards with IGF‐1 (6.7 μM, 4–6 h) reincreased capacitative Ca 2+ entry in sgk1+/+ MTF, whereas in sgk1−/− cells it remained unchanged. In conclusion, lack of SGK1 does not abrogate Kv channel activity but abolishes regulation of those channels by serum, glucocorticoids and IGF‐1, an effect influencing capacitative Ca 2+ entry. © 2004 Wiley‐Liss, Inc.
Simultaneous reverse saturable absorption of fluorinated naphthalocyanines at 532 and 1064 nm
2004-12-16

The series of (tert-butyl)catechol-substituted fluorinated naphthalocyanines 1, 2 and 3 displays limiting of the optical power generated with nanosecond light pulses simultaneously at 532 and 1064 nm. Limiting thresholds of 1-3 fall in the range 1.5-2.7 J cm<sup>-2</sup> at 532 nm and 2.6-3.7 J cm<sup>-2</sup> at 1064 nm when linear transmittance is 0.75 at both wavelengths of analysis. Compared to other unsubstituted naphthalocyanines, 1-3 show a relatively large window of high linear optical transmission between the characteristic Q- and B- absorption bands (above 0.75 for a 250 nm-wide window when 1-3 concentration is in the order of few millimoles per liter in 1 cm thick cells). A general enhancement of photostability in 1-3 is observed for the presence of electron-withdrawing fluorine substituents. The optical limiting effect produced by these systems is evaluated for the protection of optical sensors which operate in both visible and NIR spectral ranges, e.g. the human eye and night vision devices.
A concept for the clinical implementation of sentinel lymph node biopsy in patients with breast carcinoma with special regard to quality assurance
2004-12-20

Abstract The development of standardized and reproducible clinical pathways is an important precondition for quality assurance in medicine, especially if a new method has not yet been ultimately validated. Sentinel lymph node biopsy (SLNB) is a widely accepted new surgical procedure in the treatment of early breast carcinoma. However, numerous steps of the method and details of the technique are not standardized and, thus, hamper quality assurance for SLNB. The German Society of Senology appointed an interdisciplinary consensus committee to work out guidelines for the standardized performance and quality‐assured implementation of SLNB on a nationwide, homogeneous standard. The committee consisted of surgeons, gynecologists, radiooncologists, nuclear physicians, oncologists, and pathologists. Relevant questions related to patient selection, lymphatic mapping, surgery, histopathologic work‐up, further local and systemic treatment decisions, patient information, training, and follow‐up were evaluated with respect to clinical evidence, objectivity, and reproducibility. Clinical pathways were developed on the basis of this analysis. Requirements to the performing institutions and surgeons were defined. Cancer 2005. © 2004 American Cancer Society.
The crystal structure of yeast copper thionein: The solution of a long-lasting enigma
2004-12-21

We report here the crystal structure of yeast copper thionein (Cu-MT), determined at 1.44-Å resolution. The Cu-MT structure shows the largest known oligonuclear Cu(I) thiolate cluster in biology, consisting of six trigonally and two digonally coordinated Cu(I) ions. This is at variance with the results from previous spectroscopic determinations, which were performed on MT samples containing seven rather than eight metal ions. The protein backbone has a random coil structure with the loops enfolding the copper cluster, which is located in a cleft where it is bound to 10 cysteine residues. The protein structure is somewhat different from that of Ag 7 -MT and similar, but not identical, to that of Cu 7 -MT. Besides the different structure of the metal cluster, the main differences lie in the cysteine topology and in the conformation of some portions of the backbone. The present structure suggests that Cu-MT, in addition to its role as a safe depository for copper ions in the cell, may play an active role in the delivery of copper to metal-free chaperones.
Effects of prolactin and cortisol on natural killer (NK) cell surface expression and function of human natural cytotoxicity receptors (NKp46, NKp44 and NKp30)
2004-12-21

Summary The surface density of the triggering receptors (e.g. NKp46 and NKp30) responsible for natural killer (NK) cell-mediated cytotoxicity determines the ability of NK cells to kill susceptible target cells. In this study, we show that prolactin up-regulates and cortisol down-regulates the surface expression of NKp46 and NKp30. The prolactin-mediated activation and the cortisol-mediated inhibition of natural cytotoxicity receptor (NCR) surface expression reflects gene regulation at the transcriptional level. NKp46 and NKp30 are the major receptors involved in the NK-mediated killing of K562, a human chronic myelogenous leukaemia cell line. Accordingly, the prolactin dramatically increased the NK-mediated killing of the K562 cell line, whereas cortisol abolished this activity. Our data suggest a mechanism by which prolactin activates the lytic function of NK cells, and cortisol inhibits the NK-mediated attack.
Mass Spectrometric Investigations of the Dissociation of [C@W6Cl17]− Ions in the Gas Phase
2004-12-21

A clean break: A carbon-centered tungsten cluster [C@W6Cl18]2− (see picture: C orange, Cl green, W blue) was examined by mass spectrometry and its decomposition studied by collisionally activated dissociation experiments. A retrosynthesis-type dissociation sequence which gives indications about the mechanism of formation is observed. The bonding of the carbon atoms in the center of the tungsten framework shows parallels to the bonding in tungsten carbide.
Mastocytosis: Pathology, genetics, and current options for therapy
2004-12-22

Mast cell disorders are defined by an abnormal accumulation of tissue mast cells (MCs) in one or more organ systems. Symptoms in mastocytosis result from MC-derived mediators and, less frequently, from destructive infiltration of MCs. Cutaneous mastocytosis (CM) is a benign disease of the skin and may regress spontaneously. Systemic mastocytosis (SM) is a persistent disease in which a somatic c-kit mutation at codon 816 is usually detectable in MCs and their progenitors. The clinical course in these patients is variable ranging from asymptomatic for years to highly aggressive and rapidly devastating. The WHO discriminates five categories of SM: indolent SM (ISM), aggressive SM (ASM), SM with associated clonal hematological non-MC-lineage disease (AHNMD), and mast cell leukemia (MCL). The c-kit mutation D816V is quite common and may be found in all SM-categories. In SM-AHNMD, additional genetic abnormalities have been reported, whereas no additional defects are yet known for ASM or MCL. Patients with ISM and CM are treated with "mediator-targeting" drugs, whereas patients with ASM or MCL are candidates for cytoreductive therapy. The use of "Kit-targeting" tyrosine kinase inhibitors such as STI571 (Imatinib, Gleevec), has also been suggested. However, the D816V mutation of c-kit is associated with relative resistance against STI571. Therefore, these patients require alternative targeted drugs or new drug-combinations. In patients with SM-AHNMD, separate treatment plans for the SM-component and the AHNMD should be established. Examples include the use of STI571 in patients with SM plus hypereosinophilic syndrome (SM-HES) and the FIPL1/PDGFRA fusion gene target, or chemotherapy for eradication of AML in patients with SM-AML.
Evidence for a protective role of Mcl-1 in proteasome inhibitor-induced apoptosis
2004-12-22

Abstract Proteasome inhibitors exhibit antitumor activity against malignancies of different histology. Yet, the mechanisms underlying this effect are poorly understood. Recent evidence indicates that antiapoptotic factors may also accumulate as a consequence of exposure to these drugs, possibly reducing their cytotoxicity. These include the Bcl-2 family member Mcl-1, whose down-regulation has been proposed to initiate apoptosis in response to genotoxic stimuli. In this study, we found that proteasome inhibitors release cyotochrome c and second mitochondria-derived activator of caspase (SMAC)/Diablo and trigger the subsequent apoptotic cascade in spite of concomitant Mcl-1 increase. However, our data indicate that subtraction of Mcl-1 during apoptosis, although not required for early release of proapoptotic factors, is probably relevant in speeding up cell demise, since RNA interference-mediated Mcl-1 silencing is lethal in lymphoma cells. Consistent with this, the cytotoxic effects of proteasome inhibitors are enhanced when Mcl-1 increase is impeded. Thus, this study identifies Mcl-1 accumulation as an unwanted molecular consequence of exposure to proteasome inhibitors, which slows down their proapoptotic effects. Pharmacologic or genetic approaches targeting Mcl-1, including therapeutic RNAi, may increase the effectiveness of these compounds. (Blood. 2005;105:3255-3262)
NO ABERRANT METHYLATION OF NEUROFIBROMATOSIS 1 GENE (NF1) PROMOTER IN PILOCYTIC ASTROCYTOMA IN CHILDHOOD
2004-12-22

Tumors of the central nervous system are the most frequent solid tumors in childhood. With 30-40% of this heterogenous group, low-grade astrocytomas represent the most common subtype. Neurofibromatosis type 1 (NF1) is strongly associated with the development of pilocytic astrocytoma (PA), frequently appearing as optic glioma. Neurofibromatosis 1 gene (NF1 ) fulfills the criteria of a tumor suppressor gene and is deleted or mutated heterozygously in patients with NF1. This suggests an involvement in the development of PA. To clarify whether silencing of NF1 by promoter methylation plays a role in PA and especially in optic glioma, the authors investigated the methylation status in 30 PA, 6 of which had optic glioma. However, no methylation was found at the NF1 promoter region in PA. To rule out that silencing of NF1 by promoter methylation is restricted to higher-grade astrocytomas, 15 pediatric WHO II degree and IV degree astrocytomas were analyzed: 12 astrocytomas II and 3 glioblastomas displayed no NF1 promoter methylation. The authors conclude that NF1 silencing by methylation plays no role in low-grade astrocytoma.
Thermoluminescence screening of non‐diagnostic sherds from stream sediments to obtain a preliminary alluvial chronology: An example from Cyprus
2004-12-22

Abstract In this paper, simple thermoluminescence (TL) dating procedures utilizing non‐diagnostic sherds from fluvial deposits are described. This approach may provide preliminary insights into the chronology of fluvial sequences in areas where transported ceramics are common, but alluvial chronologies are not well developed. Our method deviates from conventional TL‐ dating methods in that simple screening measurements are made from small, heavily abraded sherds, and dose rates are estimated rather than being measured from each sample. This results in rapid and inexpensive laboratory measurements, which can be used to support field surveys. The limitations in precision and accuracy relative to quantitative luminescence procedures are discussed. It is argued that the results can be used to estimate an approximate maximum age of alluvial deposition events. The approach is illustrated with results from a geoarchaeological survey in Cyprus. © 2005 Wiley Periodicals, Inc.
The Forkhead-associated Domain Protein Cep170 Interacts with Polo-like Kinase 1 and Serves as a Marker for Mature Centrioles
2004-12-23

We report the characterization of Cep170, a forkhead-associated (FHA) domain protein of previously unknown function. Cep170 was identified in a yeast two-hybrid screen for interactors of Polo-like kinase 1 (Plk1). In human cells, Cep170 is constantly expressed throughout the cell cycle but phosphorylated during mitosis. It interacts with Plk1 in vivo and can be phosphorylated by Plk1 in vitro, suggesting that it is a physiological substrate of this kinase. Both overexpression and small interfering RNA (siRNA)-mediated depletion studies suggest a role for Cep170 in microtuble organization and cell morphology. Cep170 associates with centrosomes during interphase and with spindle microtubules during mitosis. As shown by immunoelectron microscopy, Cep170 associates with subdistal appendages, typical of the mature mother centriole. Thus, anti-Cep170 antibodies stain only one centriole during G1, S, and early G2, but two centrioles during late G2 phase of the cell cycle. We show that Cep170 labeling can be used to discriminate bona fide centriole overduplication from centriole amplification that results from aborted cell division.
Processing and presentation of HLA class I and II epitopes by dendritic cells after transfection with in vitro–transcribed MUC1 RNA
2004-12-24

Abstract RNA transfection of dendritic cells (DCs) was shown to be highly efficient in eliciting CD8+ and CD4+ T-cell responses. However, antigen presentation pathways involved in generation of human leukocyte antigen (HLA) class I and class II peptides have remained elusive. To analyze this we incubated mucin 1 (MUC1) RNA-transfected DCs with compounds known to inhibit HLA class I presentation and used these cells in chromium 51 (51Cr)–release assays. As effectors, we used cytotoxic T lymphocyte (CTL) lines specific for the MUC1 peptides M1.1 and M1.2. We observed that the presentation of HLA-A*02 epitopes is inhibited by brefeldin A and lactacystin. To determine the requirement of a functional transporter associated with antigen processing (TAP), we cotransfected DCs with MUC1 and infected cell peptide 47 (ICP47) RNA. ICP47 could only inhibit the presentation of the M1.1 but not the M1.2 peptide, indicating that this epitope derived from the signal sequence is presented independently of TAP. Cocultivation of MUC1 RNA-transfected DCs with MUC1-specific CD4+ T lymphocytes revealed that the presentation of HLA class II peptides is sensitive to proteasomal inhibitors and brefeldin A. Furthermore, the presentation pathway requires lysosomal and endosomal processing and is mediated by autophagy. Our results demonstrate that the efficient presentation of cytosolic proteins on major histocompatibility complex (MHC) class II combines the proteolytic and lysosomal pathways.
Mistletoe lectin I in complex with galactose and lactose reveals distinct sugar-binding properties
2004-12-24

The structures of mistletoe lectin I (ML-I) from Viscum album complexed with lactose and galactose have been determined at 2.3 A resolution and refined to R factors of 20.9% (Rfree = 23.6%) and 20.9 (Rfree = 24.6%), respectively. ML-I is a heterodimer and belongs to the class of ribosome-inactivating proteins of type II, which consist of two chains. The A-chain has rRNA N-glycosidase activity and irreversibly inhibits eukaryotic ribosomes. The B-chain is a lectin and preferentially binds to galactose-terminated glycolipids and glycoproteins on cell membranes. Saccharide binding is performed by two binding sites in subdomains alpha1 and gamma2 of the ML-I B-chain separated by approximately 62 A from each other. The favoured binding of galactose in subdomain alpha1 is achieved via hydrogen bonds connecting the 4-hydroxyl and 3-hydroxyl groups of the sugar moiety with the side chains of Asp23B, Gln36B and Lys41B and the main chain of 26B. The aromatic ring of Trp38B on top of the preferred binding pocket supports van der Waals packing of the apolar face of galactose and stabilizes the sugar-lectin complex. In the galactose-binding site II of subdomain gamma2, Tyr249B provides the hydrophobic stacking and the side chains of Asp235B, Gln238B and Asn256B are hydrogen-bonding partners for galactose. In the case of the galactose-binding site I, the 2-hydroxyl group also stabilizes the sugar-protein complex, an interaction thus far rarely detected in galactose-specific lectins. Finally, a potential third low-affinity galactose-binding site in subunit beta1 was identified in the present ML-I structures, in which a glycerol molecule from the cryoprotectant buffer has bound, mimicking the sugar compound.
Direct Urca neutrino radiation from superfluid baryonic matter
2004-12-24

Dense matter in compact stars cools efficiently by neutrino emission via the direct Urca processes n -> p + e + nu and p + e -> n + nu. Below the pairing phase transition temperature Tc these processes are suppressed - at asymptotically low temperatures exponentially. We compute the emissivity of the Urca process at one loop for temperatures T < Tc, in the case where the baryons are paired in the 1S0 partial wave. The Urca process is suppressed linearly, rather than exponentially, within the temperature range 0.1 < T/Tc < 1. The charge-current Cooper pair-breaking process contributes up to 50% of the total Urca emissivity in this temperature range.
Chemical reactions at Cu∕ZnS(001) and In∕ZnS(001) heterojunctions: A comparison of photoelectron and SL2,3 x-ray emission spectroscopy
2004-12-27

Occurrence and extent of chemical reactions at Cu∕ZnS(001) and In∕ZnS(001) heterojunctions have been investigated by SL2,3 x-ray emission spectroscopy as well as photoelectron spectroscopy. With the formation of metal-sulfur bonds, spectral features originating from shallow metal d core levels (Zn3d, In4d) or valence states (Cu3d)) may appear in the SL2,3 emission spectra. Thus the x-ray emission spectroscopy was employed to detect chemical reactions at the heterojunctions, together with conventional photoelectron spectroscopy. Considerable reactions at the Cu∕ZnS(001) interface are more clearly indicated in the SL emission spectrum than in the Cu2p3∕2 or S2p core level spectra, whereas relatively confined reactions at the In∕ZnS(001) interface can only be probed in the In3d5∕2 core level spectra. The partial densities of states calculated for a reference CuInS2 on the basis of density functional theory agree well with features occurring in its SL2,3 emission spectrum.
Sudden cardiac death in myotonic dystrophy type 2
2004-12-28

Medical records and follow-up data were reviewed in 297 genetically proven myotonic dystrophy type 2 (DM2) patients. Patients were selected by the criteria of cardiac sudden death before age 45. Sudden death occurred in four patients, three of whom were cardiological asymptomatic, and one with a history of heart failure. Cardiac histopathology showed dilated cardiomyopathy in all, and conduction system fibrosis in two patients. Pathogenetic CCUG ribonuclear inclusions were demonstrable in cardiomyocytes.
Decorin Modulates Wound Healing in Experimental Glaucoma Filtration Surgery: A Pilot Study
2004-12-28

The data of this pilot study suggest that perioperative subconjunctival decorin applications significantly affect conjunctival scarring and surgical outcome of glaucoma filtration treatments in rabbits.
Antibodies against glycosylated native MOG are elevated in patients with multiple sclerosis
2004-12-28

Antibodies against native glycosylated myelin-oligodendrocyte-glycoprotein (MOG) were measured by ELISA in patients with multiple sclerosis (MS) and controls. Anti-MOG IgM antibodies were elevated during the first demyelinating event. Higher MOG-specific IgG antibodies were found in patients during relapses and in secondary chronic progressive MS compared to patients in remission and healthy controls. Antibodies against native MOG may be a potential biomarker for MS.
A thermal-dissipation-based approach for balancing data load in distributed hash tables
2004-12-28

A major objective of peer-to-peer (P2P) systems is the management of large amounts of data distributed across many systems. Distributed hash tables (DHT) are designed for highly scalable, self-organizing, and efficient distribution and lookup of data, whereby data is stored globally persistent. The range of values of the corresponding hash function is partitioned and each interval is assigned to a node of the DHT. Because the assignment of data to nodes is based on hash functions, one assumes that the respective data load is distributed evenly across all participating nodes. However most DHT show difficulties with load balancing as we demonstrate in this paper. As a solution for this problem, we present a new and very simple approach for balancing stored data between peers in a fashion analogous to the dissipation of heat energy in materials. We compare this algorithm with other approaches for load balancing and present results based on simulations and a prototype implementation. This new algorithm improves the distribution of load in DHT without requiring major changes of the DHT themselves. In addition, we show that the fault tolerance of peer-to-peer systems is increased by the proposed algorithm.