julilili42/papers huggingface dataset:
Elk‐1 knock‐out mice engineered by Flp recombinase‐mediated cassette exchange
2004-01-26

Abstract Elk‐1 is a member of the TCF subfamily of Ets proteins. TCFs interact with SRF at serum response elements (SREs) of immediate early genes (IEGs), such as c‐fos and Egr‐1 , thereby mediating IEG induction upon extracellular stimulation. We previously generated an Elk‐1 null allele ( Elk1‐137 ) in murine embryonic stem (ES) cells by homologous recombination. In Elk1‐137 , the Elk‐1 gene was replaced by a Hygromycin B phosphotransferase – Thymidine Kinase ( HygTk ) fusion gene, flanked by two nonidentical Flp recombinase recognition (FRT) sites (Cesari et al. , [2004] Mol Cell Biol, in press) to allow for the subsequent generation of alternative alleles of interest by recombinase‐mediated cassette exchange (RMCE). Elk1‐deficient mice derived from Elk‐1 ( 137/0 ) ES cells are viable and do not reveal strong phenotypical abnormalities, apart from male sterility. However, the Elk‐1 locus contains the Tk cassette, which has previously been related to this defect. Therefore, in our first experiment involving the technique of Flp RMCE we chose to remove the HygTk cassette in Elk‐1 ( 137/0 ) ES cells and to generate Elk‐1 ( RMCE16/0 ) and Elk‐1 ( RMCE16/RMCE16 ) mice. In so doing, we provide evidence that the sterility of Elk1 ( 137/0 ) mice was not due to the absence of Elk‐1 but rather the presence of HygTk . This is the first report of mice derived from ES cells which were subjected to Flp RMCE and thus proves that RMCE is a powerful tool for the genetic engineering of previously tagged loci in the mouse genome. genesis 38:87–92, 2004. © 2004 Wiley‐Liss, Inc.
Perisynaptic Schwann cells of the vertebrate motor endplate bear modified cilia
2004-01-26

Abstract Perisynaptic Schwann cells (PSCs), descendants of the myelinating Schwann cells, cover the axon terminal of the vertebrate motor endplate of the skeletal muscle fiber. PSCs are assumed to support the function of the axon terminal. This function suggests a net material transport in the direction of the axon terminal. Morphologically it is to be expected that these cells have a cytoskeleton aligned to the axon terminal. Investigations clarifying this statement have not yet been undertaken. From previous investigations we know, however, that the PSCs have a microtubule‐organizing center, which is a part of this cytoskeleton. The centrioles of the organizing center may also participate in the formation of a modified cilium structure whose function is unknown. In the present investigation, characteristic ultrastructural features of the modified cilium structure and its relationship to the Golgi apparatus and the axon terminal are presented. A function for the modified cilium structure is discussed. Microsc. Res. Tech. 63:149–154, 2004. © 2004 Wiley‐Liss, Inc.
Long term variability of Cyg X-1
2004-01-27

\\n We study the long term evolution of the relationship between the\\n root mean square (rms) variability and flux (the “rms-flux relation”)\\n for the black hole Cygnus X-1 as monitored from 1996 to 2003 with the\\n Rossi X-ray Timing Explorer (<sans-serif>RXTE</sans-serif>). We confirm earlier results by\\n [CITE] of a linear relationship between rms and flux in the\\n hard state on time scales &gt;5 s reflecting in its slope the\\n fractional rms variability. We demonstrate the perpetuation of the linear\\n rms-flux relation in the soft and the intermediate state. The existence\\n of a non-zero intercept in the linear rms-flux relation argues for two\\n lightcurve components, for example, one variable and one non-variable\\n component, or a possible constant rms component. The relationship between\\n these two hypothesized components can be described by a fundamental\\n dependence of slope and intercept at time scales 10 ksec with\\n long term averages of the flux. \\n \\n
Severe congenital myopathy with Möbius, Robin, and Poland sequences: New aspects of the Carey–Fineman–Ziter syndrome
2004-01-27

Abstract We report a boy with severe congenital myopathy, Möbius–Poland sequence, Robin sequence, and severe developmental delay. We consider this patient to have Carey–Fineman–Ziter syndrome. Since this is only the seventh case reported, this case helps to define further the consistent manifestations of this recognizable phenotype. Additionally our patient shows laryngostenosis, intermittent episodes of high blood pressure and Poland sequence as important clinical symptoms. © 2004 Wiley‐Liss, Inc.
Spinocerebellar ataxia type 5
2004-01-27

The authors report a German family with autosomal dominant cerebellar ataxia tightly linked to the spinocerebellar ataxia type 5 (SCA5) locus (multipoint lod score 5.76). The phenotype is characterized by a purely cerebellar syndrome with a downbeat nystagmus occurring prior to the development of other features. Imaging studies demonstrated cortical cerebellar atrophy. Progression is slow even in patients with a disease onset during the second decade. The age at onset varies from 15 to 50 years.
Object-oriented modeling and synthesis of SystemC specifications
2004-01-27

The constantly increasing complexity of today's systems demands specifications on highest levels of abstraction. In addition to a transition towards the system-level more elaborate techniques are necessary to close a growing productivity gap. Our solution to this problem is the application of the object-oriented programming paradigm together with the de facto industry standard SystemC. In this paper we show that this approach is feasible and present the integration of SystemC into a continuous object-oriented design flow. The design flow includes modeling with UML, hardware/software partitioning and synthesis of object-oriented specifications. We support our claim by results from a case study.
Determination of ( R )‐ and ( S )‐phenprocoumon in human plasma by enantioselective liquid chromatography/electrospray ionisation tandem mass spectrometry
2004-01-27

Abstract Phenprocoumon is a commonly used oral anticoagulant of the coumarin type, and has found extensive clinical use in the treatment of thrombophlebitis, pulmonary embolism and atrial fibrillation. In the course of a clinical study to investigate the influence of genetic polymorphisms of the CYP2C9 enzyme on phenprocoumon metabolism, we developed a new enantioselective liquid chromatography/electrospray ionisation tandem mass spectrometry (LC/MS/MS) method to quantify ( R )‐ and ( S )‐phenprocoumon in human plasma. HPLC separation of the enantiomers was achieved on a Chira‐Grom‐2 column under isocratic conditions using a water/acetonitrile/formic acid eluent. For detection and quantification a triple‐quadrupole MS system was used in the selected reaction monitoring (SRM) mode. As an internal standard the structurally homologous compound warfarin was chosen. The detector response was linear with a correlation coefficient of 0.988–0.999 for ( R )‐phenprocoumon and 0.989–0.999 for ( S )‐phenprocoumon in the investigated concentration range between 62.5 and 1000 ng/mL (per enantiomer). The limit of detection (LOD) was 12.5 ng/mL. Copyright © 2004 John Wiley &amp; Sons, Ltd.
NMR probing of in silico identification of anti-HPV16 E7 mAb linear peptide epitope
2004-01-27

A proteomics-based approach was exploited in order to individuate peptide sequences having the immunogenic potential to evoke humoral response. The epitope search utilized two parameters: the similarity level of the peptide sequence to the host's proteins, and the peptide capability to bind to the major histocompatibility complex class II molecules. By this approach, the human papillomavirus 16 E7(49-63) RAHYNIVTFCCKCDS peptide was individuated as the immunogenic epitope recognized by an anti-HPV16 E7 monoclonal antibody raised against the full-length viral oncoprotein. In this report, two-dimensional nuclear magnetic resonance spectroscopic experiments unequivocally probe the HPV16 E7 epitope individuation.
HE0241-0155 – Evidence for a large scale homogeneous field in a highly magnetic white dwarf
2004-01-27

In the course of the Hamburg/ESO survey we have discovered a white dwarf\\nwhose spectrum exhibits many similarities with the prototype of magnetic white\\ndwarfs Grw+70 8247. In particular several stationary line components\\nindicative for magnetic fields between about 150 and 400 MG are found in both\\nobjects. However, the features between 5000 and 5500 \\\\AA in the spectrum of\\nHE0241-0155 cannot be explained by stationary line components and demand a\\nrelatively homogeneous magnetic field with clustering around 200 MG. For this\\nreason a pure dipole model failed to reproduce this spectral region.An\\noffset-dipole configuration led to some improvement in the fit but a good\\nagreement was only possible for a geometry -- described by an expansion into\\nspherical harmonics -- where most of the surface is covered with magnetic field\\nstrengths strongly clustered around 200 MG. This may indicate the presence of a\\nlarge magnetic spot whose presence could be tested with time resolved\\nspectro-polarimetry.\\n
Osteoarthritis therapy--are there still unmet needs?
2004-01-29

Non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase (COX)-2 inhibitors are commonly used to control pain and inflammation in osteoarthritis. However, these agents have been associated with gastrointestinal, renal and cardiovascular adverse effects. Together, these complications indicate a clear unmet need in the safety of current treatment options for the management of osteoarthritis. NSAIDs are known to have adverse gastrointestinal effects, and more recently it has been suggested that some selective COX-2 inhibitors are also associated with serious gastrointestinal complications. Selective COX-2 inhibitors have a similar capacity to NSAIDs to delay ulcer healing, and may not significantly decrease the incidences of perforation, ulceration and bleeding (the most clinically relevant gastrointestinal endpoints) compared with NSAIDs. These effects may be due to overlapping roles of COX-1 and COX-2 in physiological and pathophysiological processes. Furthermore, as COX-2 is integrally involved in renal homeostasis, selective COX-2 inhibitors are associated with negative effects on kidney function similar to those seen with NSAIDs. Electrolyte disturbances, oedema and hypertension have been correlated with the use of both drug classes. Additionally, selective COX-2 inhibitors have the potential to increase cardiovascular events, although further research is required to clearly determine such a risk. With the current unmet needs in the treatment of osteoarthritis, the opportunity exists for the development of new therapies. Novel agents include the COX-inhibiting nitric oxide donors and the lipoxygenase (LOX)/COX inhibitor licofelone. Initial results suggest that these therapies may have tolerability advantages over the NSAIDs and selective COX-2 inhibitors.
Old World frog and bird vocalizations contain prominent ultrasonic harmonics
2004-01-30

Several groups of mammals such as bats, dolphins and whales are known to produce ultrasonic signals which are used for navigation and hunting by means of echolocation, as well as for communication. In contrast, frogs and birds produce sounds during night- and day-time hours that are audible to humans; their sounds are so pervasive that together with those of insects, they are considered the primary sounds of nature. Here we show that an Old World frog (Amolops tormotus) and an oscine songbird (Abroscopus albogularis) living near noisy streams reliably produce acoustic signals that contain prominent ultrasonic harmonics. Our findings provide the first evidence that anurans and passerines are capable of generating tonal ultrasonic call components and should stimulate the quest for additional ultrasonic species.
Mismatch Negativity Responses in Schizophrenia: A Combined fMRI and Whole-Head MEG Study
2004-01-30

The data support the view of altered hemispheric interactions in the formation of the short-term memory traces necessary for the integration of auditory stimuli. This process is predominantly mediated by the planum temporale (secondary auditory cortex). Altered interaction of regions within the superior temporal plane and across hemispheres could be in part responsible for language-mediated cognitive (e.g., verbal memory) and psychopathological (hallucinations, formal thought disorder) symptoms in schizophrenia.
Effect of Vibrio parahaemolyticus haemolysin on human erythrocytes
2004-01-30

Haemolysin Kanagawa, a toxin from Vibrio parahaemolyticus, is known to trigger haemolysis. Flux studies indicated that haemolysin forms a cation channel. In the present study, channel properties were elucidated by patch clamp and functional significance of ion fluxes by fluorescence-activated cell sorting (FACS) analysis. Treatment of human erythrocytes with 1 U ml-1 haemolysin within minutes induces a non-selective cation permeability. Moreover, haemolysin activates clotrimazole-sensitive K+ channels, pointing to stimulation of Ca2+-sensitive Gardos channels. Haemolysin (1 U ml-1) leads within 5 min to slight cell shrinkage, which is reversed in Ca2+-free saline. Erythrocytes treated with haemolysin (0.1 U ml-1) do not undergo significant haemolysis within the first 60 min. Replacement of extracellular Na+ with NMDG+ leads to slight cell shrinkage, which is potentiated by 0.1 U ml-1 haemolysin. According to annexin binding, treatment of erythrocytes with 0.1 U ml-1 haemolysin leads within 30 min to breakdown of phosphatidylserine asymmetry of the cell membrane, a typical feature of erythrocyte apoptosis. The annexin binding is significantly blunted at increased extracellular K+ concentrations and by K+ channel blocker clotrimazole. In conclusion, haemolysin Kanagawa induces cation permeability and activates endogenous Gardos K+ channels. Consequences include breakdown of phosphatidylserine asymmetry, which depends at least partially on cellular loss of K+.
Single‐neuron evidence for a contribution of the dorsal pontine nuclei to both types of target‐directed eye movements, saccades and smooth‐pursuit
2004-01-30

Abstract The primate dorsolateral pontine nucleus (DLPN) is a key link in a cerebro‐cerebellar pathway for smooth pursuit eye movements, a pathway assumed to be anatomically segregated from tegmental circuits subserving saccades. However, the existence of afferents from several cerebrocortical and subcortical centres for saccades suggests that the DLPN and neighbouring parts of the dorsal pontine nuclei (DPN) might contribute to saccades as well. In order to test this hypothesis, we recorded from the DPN of two monkeys trained to perform smooth pursuit eye movements as well as visually and memory‐guided saccades. Out of 281 neurons isolated from the DPN, 138 were responsive in oculomotor tasks. Forty‐five were exclusively activated in saccade paradigms, 68 exclusively by smooth pursuit and 25 neurons showed responses in both. Pursuit‐related responses reflected sensitivity to eye position, velocity or combinations of velocity and position with minor contributions of acceleration in many cases. When tested in the memory‐guided saccades paradigm, 65 out of 70 neurons activated in saccade paradigms showed significant saccade‐related bursts and 20 significant activity in the memory period. Our finding of saccade‐related activity in the DPN in conjunction with the existence of strong anatomical input from saccade‐related cerebrocortical areas suggests that the DPN serves as a precerebellar relay for both pursuit and saccade‐related information originating from cerebral cortex, in addition to the classical tecto‐tegmental circuitry for saccades.
Temporary inactivation of the perirhinal cortex by muscimol injections block acquisition and expression of fear‐potentiated startle
2004-01-30

Abstract The present study examined the role of the perirhinal cortex (PRh) in aversive information processing and emotional learning. Specifically, we studied the effects of temporary inactivation of the PRh on acquisition and expression of conditioned fear as measured by fear‐potentiated startle in rats, as well as on shock sensitization of startle. Temporary inactivation of the PRh was induced by local injections of the GABA A agonist muscimol (0.0, 1.1, 2.2, 4.4 nmol/0.5 μL). Muscimol injections into the PRh blocked both the expression and acquisition of fear‐potentiated startle, as well as shock sensitization of startle. Shock sensitivity was not affected by muscimol injections, indicating that the observed blockade of acquisition and shock sensitization was not caused by a disruption in the perception of shock. Taken together, the present data show that the PRh is critical for the processing of aversive information and is necessary for the expression of emotional learning.
DEHP release from polyvinyl chloride is diminished by heparin-coating
2004-01-30

Objectives: Di-(2-ethylhexyl) phthalate (DEHP) is the most commonly used plasticizer for polyvinyl chloride (PVC) and may cause hepatic, renal and reproductive complications. This study investigated the release of plasticizers by comparing medical grade PVC with and without heparin coating and PVC with TEHTM (No-DOP) instead of DEHP as an alternative plasticizer.
Hypothermia induced platelet aggregation: No effect of aprotinin (trasylol) but inhibition by eptifibatide (integrilin)
2004-01-30

Objectives: The serine-protease inhibitor aprotinin protects platelet function during cardiopulmonary bypass. However, its safety and efficacy during deep hypothermic circulatory arrest (DHCA) is controversially discussed, and aprotinin is suspected to cause thrombosis especially during hypothermia. The platelet GP IIb/IIIa inhibitor eptifibatide has recently been shown to preserve platelet-function during cardiopulmonary bypass without increasing bleeding complications. The aim of this study was to compare the effect of aprotinin and eptifibatide on platelet-function under conditions of DHCA.
Gastroesophageal Reflux: A Critical Review of Its Role in Preterm Infants
2004-02-01

There is widespread concern about gastroesophageal reflux (GER) in preterm infants. This article reviews the evidence for this concern. GER is common in infants, which is related to their large fluid intake (corresponding to 14 L/day in an adult) and supine body position, resulting in the gastroesophageal junction’s being constantly “under water.” pH monitoring, the standard for reflux detection, is of limited use in preterm infants whose gastric pH is &amp;gt;4 for 90% of the time. New methods such as the multiple intraluminal impedance technique and micromanometric catheters may be promising alternatives but require careful evaluation before applying them to clinical practice. A critical review of the evidence for potential sequelae of GER in preterm infants shows that 1) apnea is unrelated to GER in most infants, 2) failure to thrive practically does not occur with GER, and 3) a relationship between GER and chronic airway problems has not yet been confirmed in preterm infants. Thus, there is currently insufficient evidence to justify the apparently widespread practice of treating GER in infants with symptoms such as recurrent apnea or regurgitation or of prolonging their hospital stay, unless there is unequivocal evidence of complications, eg, recurrent aspiration or cyanosis during vomiting. Objective criteria that help to identify those presumably few infants who do require treatment for GER disease are urgently needed.
A Placebo-Controlled Randomized Crossover Trial of the N-Methyl-d-Aspartic Acid Receptor Antagonist, Memantine, in Patients with Chronic Phantom Limb Pain
2004-02-01

NMDA receptors play a substantial role in central nervous system changes underlying neuropathic pain. In a placebo-controlled double-blinded study we tested the effect of 30 mg memantine on chronic phantom limb pain and pain-associated cortical reorganization.
PvUPS1, an Allantoin Transporter in Nodulated Roots of French Bean
2004-02-01

Abstract Nodulated legumes receive their nitrogen via nitrogen-fixing rhizobia, which exist in a symbiotic relationship with the root system. In tropical legumes like French bean (Phaseolus vulgaris) or soybean (Glycine max), most of the fixed nitrogen is used for synthesis of the ureides allantoin and allantoic acid, the major long-distance transport forms of organic nitrogen in these species. The purpose of this investigation was to identify a ureide transporter that would allow us to further characterize the mechanisms regulating ureide partitioning in legume roots. A putative allantoin transporter (PvUPS1) was isolated from nodulated roots of French bean and was functionally characterized in an allantoin transport-deficient yeast mutant showing that PvUPS1 transports allantoin but also binds its precursors xanthine and uric acid. In beans, PvUPS1 was expressed throughout the plant body, with strongest expression in nodulated roots, source leaves, pods, and seed coats. In roots, PvUPS1 expression was dependent on the status of nodulation, with highest expression in nodules and roots of nodulated plants compared with non-nodulated roots supplied with ammonium nitrate or allantoin. In situ RNA hybridization localized PvUPS1 to the nodule endodermis and the endodermis and phloem of the nodule vasculature. These results strengthen our prediction that in bean nodules, PvUPS1 is involved in delivery of allantoin to the vascular bundle and loading into the nodule phloem.
CMOS Monolithic Metal–Oxide Sensor System Comprising a Microhotplate and Associated Circuitry
2004-02-01

A gas sensor system fabricated in industrial CMOS technology is presented, which includes, for the first time, a microhotplate and the necessary driving and control circuitry on a single chip. Post-complementary-metal-oxide-semiconductor (CMOS) fabrication steps, such as micromachining of the membrane structure, the deposition of noble metal on the electrodes, and the processing of the sensitive metal-oxide layer, have been developed to be fully compatible with the industrial CMOS process. Temperatures up to 350/spl deg/C were reached on the hotplates using a low-voltage power supply (5 V). A symmetric hotplate design with a temperature homogeneity of better than 2% in the heated area was realized. The integrated temperature controller regulates the membrane temperature with a resolution of /spl plusmn/0.3/spl deg/C in the tracking mode. The temperature increase on the bulk chip owing to heat transfer through the membrane is less than 2% of the respective membrane operation temperature (6/spl deg/C at 350/spl deg/C membrane temperature). The gas sensing performance of the sensor was assessed by test measurements with carbon monoxide (CO). The gas tests evidenced a limit of detection of less than 5 ppm CO.