julilili42/papers huggingface dataset:
A novel contact assay for testing genotoxicity of chemicals and whole sediments in zebrafish embryos
2006-07-26

Abstract Broad consensus exists that whole-sediment exposure protocols represent the most realistic scenario to simulate in situ exposure conditions. So far, however, several endpoints including genotoxicity in vertebrate-based systems could be tested only after transfer of particle-bound substances into the aqueous phase. The present study was carried out to develop a protocol for generating a suspension of single cells from sediment-exposed zebrafish embryos that is suitable for detecting particle-bound genotoxicity in the alkaline single cell gel electrophoresis (comet assay). In this solid-phase genotoxicity assay, a whole-body cell suspension derived from zebrafish embryos exposed to native (whole) sediments is assayed in the comet assay. Several chemical and mechanical isolation procedures were compared to optimize cell yield and minimize DNA damage by the method itself. If compared to collagenase isolation, mechanical cell dissociation gave less DNA damage; trypsinization resulted in similarly low DNA damage but significantly lower cell yield. In order to test the optimized protocol, effects of well-known genotoxicants (4-nitroquinoline-N-oxide, nitrofurantoin, hydrogen peroxide, benzo[a]pyrene) and of two sediments from the upper Rhine River (Germany) on zebrafish embryos were investigated. Results documented clear-cut genotoxicity for all four substances and for one of the two whole-sediment samples. An ultraviolet (UV) light exposure of whole embryos and primary cultures from embryos elucidated only minor effects for the whole embryos compared to the primary cells. Consequently, UV irradiation cannot be suggested as a positive control in intact zebrafish embryos. In conclusion, the newly developed sediment contact assay can be recommended for the detection of both single substances but also the bioavailable fraction of the total hazard potential of sediments.
Two Psychophysical Channels of Whisker Deflection in Rats Align with Two Neuronal Classes of Primary Afferents
2006-07-26

The rat whisker system has evolved into in an excellent model system for sensory processing from the periphery to cortical stages. However, to elucidate how sensory processing finally relates to percepts, methods to assess psychophysical performance pertaining to precise stimulus kinematics are needed. Here, we present a head-fixed, behaving rat preparation that allowed us to measure detectability of a single whisker deflection as a function of amplitude and peak velocity. We found that velocity thresholds for detection of small-amplitude stimuli (&lt;3°) were considerably higher than for detection of large-amplitude stimuli (&gt;3°). This finding suggests the existence of two psychophysical channels mediating detection of whisker deflection: one channel exhibiting high amplitude and low velocity thresholds (W1), and the other channel exhibiting high velocity and low amplitude thresholds (W2). The correspondence of W1 to slowly adapting (SA) and W2 to rapidly adapting (RA) neuronal classes in the trigeminal ganglion was revealed in acute neurophysiological experiments. Neurometric plots of SA and RA cells were closely aligned to psychophysical performance in the corresponding W1 and W2 parameter ranges. Interestingly, neurometric data of SA cells fit the behavior best if it was based on a short time window integrating action potentials during the initial phasic response, in contrast to integrating across the tonic portion of the response. This suggests that detection performance in both channels is based on the assessment of very few spikes in their corresponding groups of primary afferents.
Naturally Processed Dermcidin-Derived Peptides Do Not Permeabilize Bacterial Membranes and Kill Microorganisms Irrespective of Their Charge
2006-07-26

ABSTRACT Dermcidin (DCD) is a recently described antimicrobial peptide, which is constitutively expressed in eccrine sweat glands and transported via sweat to the epidermal surface. By postsecretory proteolytic processing in sweat the dermcidin protein gives rise to several truncated DCD peptides which differ in length and net charge. In order to understand the mechanism of antimicrobial activity, we analyzed the spectrum of activity of several naturally processed dermcidin-derived peptides, the secondary structure in different solvents, and the ability of these peptides to interact with or permeabilize the bacterial membrane. Interestingly, although all naturally processed DCD peptides can adopt an α-helical conformation in solvents, they have a diverse and partially overlapping spectrum of activity against gram-positive and gram-negative bacteria. This indicates that the net charge and the secondary structure of the peptides are not important for the toxic activity. Furthermore, using carboxyfluorescein-loaded liposomes, membrane permeability studies and electron microscopy we investigated whether DCD peptides are able to permeabilize bacterial membranes. The data convincingly show that irrespective of charge the different DCD peptides are not able to permeabilize bacterial membranes. However, bacterial mutants lacking specific cell envelope modifications exhibited different susceptibilities to killing by DCD peptides than wild-type bacterial strains. Finally, immunoelectron microscopy studies indicated that DCD peptides are able to bind to the bacterial surface; however, signs of membrane perturbation were not observed. These studies indicate that DCD peptides do not exert their activity by permeabilizing bacterial membranes.
Fosmidomycin plus Clindamycin for Treatment of Pediatric Patients Aged 1 to 14 Years with Plasmodium falciparum Malaria
2006-07-26

ABSTRACT Fosmidomycin plus clindamycin was shown to be efficacious in the treatment of uncomplicated Plasmodium falciparum malaria in a small cohort of pediatric patients aged 7 to 14 years, but more data, including data on younger children with less antiparasitic immunity, are needed to determine the potential value of this new antimalarial combination. We conducted a single-arm study to improve the precision of efficacy estimates for an oral 3-day fixed-ratio combination of fosmidomycin and clindamycin at 30 and 10 mg/kg of body weight, respectively, every 12 hours for the treatment of uncomplicated P. falciparum malaria in 51 pediatric outpatients aged 1 to 14 years. Fosmidomycin plus clindamycin was generally well tolerated, but relatively high rates of treatment-associated neutropenia (8/51 [16%]) and falls of hemoglobin concentrations of ≥2 g/dl (7/51 [14%]) are of concern. Asexual parasites and fever were cleared within median periods of 42 h and 38 h, respectively. All patients who could be evaluated were parasitologically and clinically cured by day 14 (49/49; 95% confidence interval [CI], 93 to 100%). The per-protocol, PCR-adjusted day 28 cure rate was 89% (42/47; 95% CI, 77 to 96%). Efficacy appeared to be significantly reduced in children aged 1 to 2 years, with a day 28 cure rate of only 62% for this small subgroup (5/8). The inadequate efficacy in children of &lt;3 years highlights the need for continued systematic studies of the current dosing regimen, which should include randomized trial designs.
DRB1*0401-restricted human T cell clone specific for the major proinsulin73-90 epitope expresses a down-regulatory T helper 2 phenotype
2006-07-26

Recently, we have identified proinsulin (P-Ins) 73-90 as an immunodominant T cell epitope of HLA-DRB1*0401 (DR4) subjects with β-islet cell autoimmunity and of HLA-DR4/CD4 double-transgenic mice immunized with human P-Ins. We have compared the fine specificities of one human CD4 T cell clone and two mouse T cell hybridoma clones recognizing this epitope, and, although these three clones all recognized the same core region (LALEGSLQK), there were major differences in how they interacted with the peptide (p)/HLA complex, reflecting the fact that human P-Ins is a foreign antigen in the mouse and an autoantigen in the type 1 diabetes patient. The human T cell clone was forkhead transcription factor 3 (Foxp3)-positive, a marker for regulatory T cell lineages, and secreted predominantly IL-5, IL-10, and low levels of IFNγ in response to P-Ins 73-90 . This finding is compatible with the previously detected regulatory cytokine pattern in subjects with β-cell autoimmunity. However, added N- or C-terminal amino acids drastically changed HLA and tetramer binding capacity as well as T cell reactivity and the cytokine phenotype of the P-Ins 73-90 -specific human CD4 T cell clone, suggesting a potential for this P-Ins epitope as a target for therapeutic intervention in HLA-DR4-positive humans with β-islet cell autoimmunity or recent-onset type 1 diabetes.
A Targeted Protease Substrate for a Quantitative Determination of Protease Activities in the Endolysosomal Pathway
2006-07-26

Abstract Inside the cell, proteases act in concert in the degradation of proteins and peptides. In order to understand the significance of an individual proteolytic activity within an ensemble of proteases, protocols and probes are required that enable a quantitative determination of the contribution of a protease to the break‐down of a given substrate. Here we present a fluorescence resonance energy transfer‐based probe and protocols for a quantitative determination of proteolytic activities inside the endolysosomal compartment. A peptide substrate that is readily cleaved by different cathepsins is flanked by fluorescein and tetramethylrhodamine‐labeled lysine residues. Efficient endolysosomal targeting of the substrate is achieved by N‐terminal elongation with the cell‐penetrating peptide nona‐arginine. The proteasome inhibitor lactacystin has a small, but significant effect on the break‐down of the substrate, thus demonstrating that only a minor fraction of the peptide reaches the cytoplasm in its intact form. Nona‐arginine therefore constitutes a highly efficient low‐molecular‐weight moiety for targeting the endolysosomal compartment.
An algorithm for automatic determination of the respiratory phases in four-dimensional computed tomography
2006-07-26

Recently, several techniques have been developed to improve the quality of computed tomography (CT) images of the thoracic and abdominal region that are degraded by the interference of the scanning process and respiration. Several devices for respiratory-correlated CT are available for clinical usage. They are based on the synchronization of the acquired CT image data with the respiratory motion using a signal from an external respiratory monitoring system. In this work, some practical aspects of clinical implementation of the multi-slice 4D CT scanner Somatom Sensation Open (Siemens Medical Solutions, Erlangen, Germany) equipped with a respiratory gating system (RGS) AZ-733V (Anzai Medical, Tokyo, Japan) are discussed. A new algorithm developed for automatic respiratory phase determination needed for the reconstruction of the 4D CT images is presented.
Plasma Homocysteine Concentrations in Young Individuals at Increased Risk of Type 2 Diabetes are Associated with Subtle Differences in Glomerular Filtration Rate but Not with Insulin Resistance
2006-07-26

Plasma homocysteine levels are elevated in individuals with type 2 diabetes contributing to the increased cardiovascular risk of these patients. As insulin resistance is a key feature in type 2 diabetic patients, hyperhomocysteinemia might be a consequence of insulin resistance. We studied this hypothesis in 839 individuals(male: 302, female: 537, mean age: 37.5 years) with a higher prevalence of insulin resistance (positive family history of type 2 diabetes, history of gestational diabetes, overweight). Subjects with overt type 2 diabetes or known kidney disease were excluded from the study. Mean plasma homocysteine concentration was 8.9 micromol/l (95% RCI 4.8-14.9). Adjusted for age and sex we could not find a significant correlation between homocysteine levels and BMI, insulin levels, or the insulin sensitivity-index (r = 0.35; p = 0.48). Furthermore, after a successful lifestyle intervention resulting in a significant decrease in BMI, body fat content and improved insulin sensitivity (p < 0.0001 each) no differences in homocysteine concentrations could be achieved. However,in the cross-sectional analysis we found a significant and independent, negative correlation between glomerular filtration rate (GFR) and homocysteine levels (r = -0.37; p < 0.0001). In conclusion, our study did not reveal a significant association between levels of homocysteine and insulin resistance in a population with an increased risk for type 2 diabetes. However, plasma homocysteine levels were related to subtle differences in kidney function at this early stage.
A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation
2006-07-27

Abstract Numerous single‐institutional studies and a large pooled analysis have demonstrated that the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) from patients with primary, nonmetastatic breast cancer (Stages I‐III) is associated with impaired prognosis. To date, sampling of BM and assessment of DTCs is not considered a routine procedure in the clinical management of breast cancer patients; however, emerging data suggest a future role for risk stratification and monitoring of therapeutic efficacy. Because these clinical options need to be evaluated in trials to verify the principle of this concept in the clinical setting, agreement on the standardized detection of DTCs is necessary. Consequently, the German, Austrian, and Swiss Societies for Senology recently formed a panel 1) to review and discuss the existing methodologies, 2) to find a consensus for a standardized detection of DTCs, and 3) to explore the options for its clinical implementation. Cancer 2006. © 2006 American Cancer Society.
The Structure of the Major Cell Wall Polysaccharide of Bacillus anthracis Is Species-specific
2006-07-27

In this report we describe the structure of the polysaccharide released from Bacillus anthracis vegetative cell walls by aqueous hydrogen fluoride (HF). This HF-released polysaccharide (HF-PS) was isolated and structurally characterized from the Ames, Sterne, and Pasteur strains of B. anthracis. The HF-PSs were also isolated from the closely related Bacillus cereus ATCC 10987 strain, and from the B. cereus ATCC 14579 type strain and compared with those of B. anthracis. The structure of the B. anthracis HF-PS was determined by glycosyl composition and linkage analyses, matrix-assisted laser desorption-time of flight mass spectrometry, and one- and two-dimensional nuclear magnetic resonance spectroscopy. The HF-PSs from all of the B. anthracis isolates had an identical structure consisting of an amino sugar backbone of -->6)-alpha-GlcNAc-(1-->4)-beta-ManNAc-(1-->4)-beta-GlcNAc-(1-->, in which the alpha-GlcNAc residue is substituted with alpha-Gal and beta-Gal at O-3 and O-4, respectively, and the beta-GlcNAc substituted with alpha-Gal at O-3. There is some variability in the presence of two of these three Gal substitutions. Comparison with the HF-PSs from B. cereus ATCC 10987 and B. cereus ATCC 14579 showed that the B. anthracis structure was clearly different from each of these HF-PSs and, furthermore, that the B. cereus ATCC 10987 HF-PS structure was different from that of B. cereus ATCC 14579. The presence of a B. anthracis-specific polysaccharide structure in its vegetative cell wall is discussed with regard to its relationship to those of other Bacillus species.
Suprastomal tracheal stenosis after dilational and surgical tracheostomy in critically ill patients
2006-07-27

Summary We have previously reported cases of severe suprastomal stenosis after tracheostomy. In this observational study we investigated the occurrence of suprastomal stenosis as a late complication. Patients with persistent tracheostomy after intensive care underwent an endoscopic examination of tracheostoma, larynx and trachea. A percutaneous dilational tracheostomy was employed in 105 (71.9%) and surgical tracheostomy in 41 (28.1%) of the cases ( n = 146). The incidence of severe suprastomal stenosis (grade II &gt; 50% of the lumen) was 23.8% (25 of 105) after dilational tracheostomy and 7.3% (3 of 41) after surgical tracheostomy (p = 0.033). Age, gender, underlying disease, ventilation time, and swallowing ability were not significantly associated with the tracheal pathology. This study suggests that dilational tracheostomy is associated with an increased risk of severe suprastomal tracheal stenosis compared to the surgical technique.
“Occult” mastocytosis with activating c-kit point mutation evolving into systemic mastocytosis associated with plasma cell myeloma and secondary amyloidosis
2006-07-27

A case of a 70-year-old man presenting with exsudative enteropathy due to light-chain-associated amyloidosis is reported. The diagnosis of systemic mastocytosis associated with IgG/λ plasma cell myeloma and secondary generalised amyloidosis was carried out by morphological evaluation of bone marrow biopsy. The c-kit point mutation D816Y was detected by molecular analysis. Two years before, a cystadenolymphoma of the left parotid gland had been removed. A moderate increase of loosely scattered spindle-shaped mast cells, a subpopulation of them expressing CD25, an antigen that is not expressed by normal or reactive mast cells, was shown by retrospective analysis carried out on an intraparotideal lymph node. The c-kit mutation D816Y was shown by the molecular analysis of the lymph node. In summary, the notion that systemic mastocytosis may very rarely be associated with B cell neoplasms and that neoplastic mast cell infiltrates may be obscured because of only a minimal increase of atypical mast cells, which are outnumbered by other non-neoplastic cells in the same tissue, is supported by this case. This finding was preliminarily termed “occult” mastocytosis.
Discrete differential forms in general relativity
2006-07-27

A major obstacle in the numerical simulation of general relativistic spacetimes is the fact that coordinates have to be specified in order to obtain a well-defined numerical evolution. While the choice of coordinates has no impact on the geometry, it does influence the evolution in ways which are rather difficult to predict. For this reason it might be useful to devise numerical procedures which are manifestly coordinate invariant. In this paper we present an alternative way to obtain discrete versions of the Einstein equations. We formulate the Einstein equations as an exterior system in terms of differential forms. Such a formulation can be used to interpret the variables and equations in a discrete setting as discrete differential forms. We describe the basic equations and discuss the accuracy of the discrete equations.
Transient change in GABAA receptor subunit mRNA expression in Lurchercerebellar nuclei during Purkinje cell degeneration
2006-07-27

In conclusion, the down-regulation of gamma2 subunits may be related to differences in synaptic efficacy and, as such, may reflect the initial phase of adaptive responses of DCN tissue to massive GABAergic deafferentation. Its transient course, however, does not support the idea that modulations in GABAergic transmission are at the basis of the well-known DCN-based functional benefit of Lurcher mice present throughout their life.
The evaluation of stylized facial expressions
2006-07-28

Stylized rendering aims to abstract information in an image making it useful not only for artistic but also for visualization purposes. Recent advances in computer graphics techniques have made it possible to render many varieties of stylized imagery efficiently. So far, however, few attempts have been made to characterize the perceptual impact and effectiveness of stylization. In this paper, we report several experiments that evaluate three different stylization techniques in the context of dynamic facial expressions. Going beyond the usual questionnaire approach, the experiments compare the techniques according to several criteria ranging from introspective measures (subjective preference) to task-dependent measures (recognizability, intensity). Our results shed light on how stylization of image contents affects the perception and subjective evaluation of facial expressions.
Colorings and Orientations of Matrices and Graphs
2006-07-28

We introduce colorings and orientations of matrices as generalizations of the graph theoretic terms. The permanent per of certain copies of a matrix can be expressed as a weighted sum over the orientations or the colorings of . When applied to incidence matrices of graphs these equations include Alon and Tarsi's theorem about Eulerian orientations and the existence of list colorings. In the case of planar graphs we deduce Ellingham and Goddyn's partial solution of the list coloring conjecture and Scheim's equivalency between not vanishing permanents and the four color theorem. The general concept of matrix colorings in the background is also connected to hypergraph colorings and matrix choosability.
Zirconium Scandium Oxide Nitrides: Formation and Decomposition Followed in situ by XRD and Thermal Analysis.
2006-07-28

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
The cerebrocortical response to hyperinsulinemia is reduced in overweight humans: A magnetoencephalographic study
2006-07-29

Animal studies have shown that the brain is an insulin-responsive organ and that central nervous insulin resistance induces obesity and disturbances in glucose metabolism. In humans, insulin effects in the brain are poorly characterized. We used a magnetoencephalography approach during a two-step hyperinsulinemic euglycemic clamp to ( i ) assess cerebrocortical insulin effects in humans, ( ii ) compare these effects between 10 lean and 15 obese subjects, and ( iii ) test whether the insulin receptor substrate (IRS)-1 Gly972Arg polymorphism in the insulin-signaling cascade modifies these effects. Both spontaneous and stimulated (mismatch negativity) cortical activity were assessed. In lean humans, stimulated cortical activity ( P = 0.046) and the beta and theta band of spontaneous cortical activity ( P = 0.01 and 0.04) increased with insulin infusion relative to saline. In obese humans, these effects were suppressed. Moreover, the insulin effect on spontaneous cortical activity correlated negatively with body mass index and percent body fat (all r &lt; −0.4; all P &lt; 0.05) and positively with insulin sensitivity of glucose disposal (theta band, r = 0.48, P = 0.017). Furthermore, insulin increased spontaneous cortical activity (beta band) in carriers of wild-type IRS-1, whereas, in carriers of the 972Arg allele, this insulin effect was absent ( P = 0.01). We conclude that, in lean humans, insulin modulates cerebrocortical activity, and that these effects are diminished in obese individuals. Moreover, cerebrocortical insulin resistance is found in individuals with the Gly972Arg polymorphism in IRS-1, which is considered a type 2 diabetes risk gene.
Is head and neck melanoma a distinct entity? A clinical registry-based comparative study in 5702 patients with melanoma
2006-07-31

In relation to the skin surface significantly more CMMs were found in the head and neck area than in other anatomical regions. This might indicate, but does not prove, that UV exposure promotes the development of CMM. Although HNM showed specific clinicopathological features, prognosis remained unaffected. Thus HNM seems not to be a distinct subtype of CMM.