julilili42/papers huggingface dataset:
Prognostic Value of Minimal Residual Disease Quantification by Real-Time Reverse Transcriptase Polymerase Chain Reaction in Patients With Core Binding Factor Leukemias
2003-11-26

Purpose: In patients with acute myeloblastic leukemia with t(8;21) or inv(16) aberrations (core binding factor [CBF] leukemias), minimal residual disease (MRD) can be sensitively detected during and after chemotherapy by use of molecular methods. However, the prognostic impact of qualitative MRD detection is still under debate. In this study, the prognostic value of MRD quantification in patients with CBF leukemias was assessed. Patients and Methods: We quantified MRD at various time points during and after therapy by real-time reverse transcriptase polymerase chain reaction (RT-PCR) for AML1/MTG8 and CBFB/MYH11 in 37 patients with CBF leukemias treated within a multicenter trial. Results: At initial diagnosis, the patients showed a heterogenous fusion gene expression relative to glyceraldehyde 3-phosphate dehydrogenase with a variation of more than two log steps. According to MRD status during/after therapy, two groups of patients were separated. Of the 26 patients who had MRD levels of less than 1% in relation to initial diagnosis at all time points tested after induction chemotherapy, only two experienced relapse after a median follow-up of 19 months. Of the 11 patients who had a sample with an MRD level ≥ 1% at least at one time point after induction therapy, 10 experienced relapse, with a median remission duration of 10 months (P &lt; .001). The median interval between the informative MRD sample and clinical relapse in these patients was 3 months. Conclusion: MRD quantification by real-time RT-PCR allows the identification of patients with a high risk of relapse among the CBF leukemias.
Gene Knockout Models
2003-11-27

Introduction Gene Knockout Mice ES Cells Targeting Vector Selection of Recombinant ES Cells Injection of Recombinant ES Cells into Blastocysts and Blastocyst Transfer to Pseudopregnant Recipients Chimeras and F1 and F2 Offspring Tissue-Specific Gene Expression Ligand-Activated CRE Recombinases The Tetracycline/Doxycycline-Inducible Expression System Transgenic Mice Targeted Gene Disruption in Drosophila Targeted Gene Knockdown in Zebrafish Targeted Caenorhabditis Elegans Deletion Strains References
Role of Ca2+-activated K+ channels in human erythrocyte apoptosis
2003-12-01

Exposure of erythrocytes to the Ca 2+ ionophore ionomycin has recently been shown to induce cell shrinkage, cell membrane blebbing, and breakdown of phosphatidylserine asymmetry, all features typical of apoptosis of nucleated cells. Although breakdown of phosphatidylserine asymmetry is thought to result from activation of a Ca 2+ -sensitive scramblase, the mechanism and role of cell shrinkage have not been explored. The present study was performed to test whether ionomycin-induced activation of Ca 2+ -sensitive Gardos K + channels and subsequent cell shrinkage participate in ionomycin-induced breakdown of phosphatidylserine asymmetry of human erythrocytes. According to on-cell patch-clamp experiments, ionomycin (1 μM) induces activation of inwardly rectifying K + -selective channels in the erythrocyte membrane. Fluorescence-activated cell sorter analysis reveals that ionomycin leads to a significant decrease of forward scatter, reflecting cell volume, an effect blunted by an increase of extracellular K + concentration to 25 mM and exposure to the Gardos K + channel blockers charybdotoxin (230 nM) and clotrimazole (5 μM). As reflected by annexin binding, breakdown of phosphatidylserine asymmetry is triggered by ionomycin, an effect again blunted, but not abolished, by an increase of extracellular K + concentration and exposure to charybdotoxin (230 nM) and clotrimazole (5 μM). Similar to ionomycin, glucose depletion leads (within 55 h) to annexin binding of erythrocytes, an effect again partially reversed by an increase of extracellular K + concentration and exposure to charybdotoxin. K-562 human erythroleukemia cells similarly respond to ionomycin with cell shrinkage and annexin binding, effects blunted by antisense, but not sense, oligonucleotides against the small-conductance Ca 2+ -activated K + channel isoform hSK4 (KCNN4). The experiments disclose a novel functional role of Ca 2+ -sensitive K + channels in erythrocytes, i.e., their participation in regulation of erythrocyte apoptosis.
Induced Gamma-Band Activity and Human Brain Function
2003-12-01

Oscillatory activity in the gamma-band range has been related both to gestalt perception and to cognitive functions such as attention, learning, and memory. After giving a brief account of recent findings from electroencephalography and intracortical recordings, the present review will focus on spectral activity in the magnetoencephalogram. Here, gamma-band effects are topographically more local and involve higher frequencies than in the electroencephalogram. Bottom-up-driven auditory spatial mismatch detection elicits gamma-band activity over posterior parietal cortex, whereas auditory pattern mismatch processing leads to gamma-band enhancements over anterior temporal and inferior frontal regions. These topographies support representations of auditory spatial and pattern information in the putative dual auditory “where” and “what” pathways, respectively. During top-down-guided auditory spatial and pattern-working memory tasks, prefrontal gamma-band increases are observed in addition to activations over putative auditory stream areas. Moreover, stimulus maintenance in working memory is accompanied by coherence increases between sensory and prefrontal regions. Gamma-band topographies in magnetoencephalogram are highly comparable with hemodynamic brain imaging studies but yield additional information on the temporal dynamics of activations and connectivity patterns. In summary, magnetoencephalographic gammaband activity revealed both local synchronization patterns and cortico-cortical interactions accompanying cognitive processes at a good spatial and high temporal resolution.
Understanding and Treating “Pusher Syndrome”
2003-12-01

“Pusher syndrome” is a clinical disorder following left or right brain damage in which patients actively push away from the nonhemiparetic side, leading to a loss of postural balance. The mechanism underlying this disorder and its related anatomy have only recently been identified. Investigation of patients with severe pushing behavior has shown that perception of body posture in relation to gravity is altered. The patients experience their body as oriented “upright” when the body actually is tilted to the side of the brain lesion (to the ipsilesional side). In contrast, patients with pusher syndrome show no disturbed processing of visual and vestibular inputs determining visual vertical. These new insights have allowed the authors to suggest a new physical therapy approach for patients with pusher syndrome where the visual control of vertical upright orientation, which is undisturbed in these patients, is the central element of intervention.
A travel time based hydraulic tomographic approach
2003-12-01

Hydraulic tomography is a method to identify the three‐dimensional spatial distribution of hydraulic properties in the subsurface. We propose a tomographic approach providing the inversion of travel times of hydraulic or pneumatic tests conducted in a tomographic array. The inversion is based on the relation between the peak time of a recorded transient pressure curve and the diffusivity of the investigated system. The development of a transformation factor enables the inversion of further travel times besides the peak time of a transient curve. As the early travel times of the curve are mainly related to preferential flow features while the inversion based on late travel times are reflecting an integral behavior, it can be assumed that the different inversion results reflect the properties of the overall system. By comparing the different reconstructions the system interpretation therefore becomes more comprehensive and reliable. Furthermore, the similarity of the proposed hydraulic tomographic approach to seismic travel time tomography allows us to apply the inversion algorithms which are used for seismic tomography. We therefore apply the method of staggered grids, which enables to refine the grid resulting in a higher nominal resolution, to data from a set of interference tests arranged in a tomographic array. The tests were conducted in an unsaturated fractured sandstone cylinder in the laboratory. The three‐dimensional reconstructions of the diffusivity distribution are found to be highly reliable and robust. In particular, the mapped fracture of the sandstone cylinder coincides with our reconstructed diffusivity distribution.
Moderate degradation does not preclude microarray analysis of small amounts of RNA
2003-12-01

Gene expression analysis by microarrays using small amounts of RNA is becoming more and more popular against the background of advances and increasing importance of small-sample acquisition methods like laser microdissection techniques. The quality of RNA preparations from such samples constitutes a frequent issue in this context. The aim of this study was to assess the impact of different extents of RNA degradation on the expression profile of the samples. We induced RNA degradation in human tumor and healthy tissue samples by endogeneous ribonucleases. Next, we amplified 20 ng total RNA degraded to different extents by two rounds of in vitro transcription and analyzed them using Affymetrix oligonucleotide microarrays. Expression differences for some genes were independently confirmed by real-time quantitative PCR. Our results suggest that gene expression profiles obtained from partially degraded RNA samples with still visible ribosomal bands exhibit a high degree of similarity compared to intact samples and that RNA samples of suboptimal quality might therefore still lead to meaningful results if used carefully.
Plasma Adiponectin and Endogenous Glucose Production in Humans
2003-12-01

OBJECTIVE—High plasma adiponectin is associated with reduced risk of type 2 diabetes, probably a consequence of its insulin-sensitizing properties. In vivo data in rodents suggest that the insulin-sensitization responsible for improvement of glycemia occurs in muscle and liver. Whereas associations of plasma adiponectin with muscle insulin sensitivity in humans have been examined, this has not been done for the liver. RESEARCH DESIGN AND METHODS—We therefore analyzed the relationship between fasting plasma adiponectin and basal endogenous glucose production [EGP]-basal) and insulin-suppressed EGP (EGP-insulin, isotope dilution technique) in 143 Pima Indians (94 with normal glucose tolerance, 36 with impaired glucose tolerance, and 16 with type 2 diabetes). RESULTS—Fasting plasma adiponectin concentrations were negatively correlated with EGP-basal and EGP-insulin before (P = 0.006 and P &amp;lt; 0.0001, respectively) as well as after adjustment for age, sex, percent body fat, and insulin-stimulated whole-body glucose uptake (P = 0.007 and P = 0.0005, respectively). CONCLUSIONS—These findings are compatible with the hypothesis that adiponectin increases hepatic insulin sensitivity. Consistent with data in animals, adiponectin may have generalized insulin-sensitizing effects in humans.
Cortisol has different effects on human memory for emotional and neutral stimuli
2003-12-01

Adrenal stress hormones are considered to play a role in memory enhancement of emotionally arousing events. To investigate the effects of cortisol on human emotional memory, subjects were administered hydrocortisone (25 mg) or placebo and presented with either an emotionally arousing or a neutral story. Memory for the story was tested 1 week later. In all memory tests, subjects who viewed the emotional story scored better for the emotionally arousing story parts, indicating that arousal enhances memory. In memory of details, cortisol showed an interaction with story valence but no main effect: cortisol enhanced memory for details of the neutral story version, but impaired memory for details of the emotionally arousing version. We thus confirm a non-linear interaction between cortisol and arousal on memory formation.
Identification of an apical Cl-/HCO3-exchanger in gastric surface mucous and duodenal villus cells
2003-12-01

The molecular identity of the apical HCO 3 - -secreting transporter in gastric mucous cells remains unknown despite its essential role in preventing injury and ulcer by gastric acid. Here we report the identification of a Cl - /HCO 3 - exchanger that is located on apical membranes of gastric surface epithelial cells. RT-PCR studies of mouse gastrointestinal tract mRNAs demonstrated that this transporter, known as anion exchanger isoform 4 (AE4), is expressed in both stomach and duodenum. Northern blot analysis of RNA from purified stomach epithelial cells indicated that AE4 is expressed at higher levels in mucous cells than in parietal cells. Immunoblotting experiments identified AE4 as a ∼110- to 120-kDa protein in membranes from stomach epithelium and apical membranes from duodenum. Immunocytochemical staining demonstrated that AE4 is expressed in apical membranes of surface cells in both mouse and rabbit stomach and duodenum. Functional studies in oocytes indicated that AE4 functions as a Cl - /HCO 3 - exchanger. These data show that AE4 is an apical Cl - /HCO 3 - exchanger in gastric mucous cells and duodenal villus cells. On the basis of its function and location, we propose that AE4 may play an important role in mucosal protection.
Influence of Two Wolbachia Strains on Population Structure of East AfricanDrosophila simulans
2003-12-01

Abstract Drosophila simulans is hypothesized to have originated in continental East Africa or Madagascar. In this study, we investigated evolutionary forces operating on mitochondrial DNA (mtDNA) in populations of D. simulans from Zimbabwe, Malawi, Tanzania, and Kenya. Variation in mtDNA may be affected by positive selection, background selection, demographic history, and/or any maternally inherited factor such as the bacterial symbiont Wolbachia. In East Africa, the wRi and wMa Wolbachia strains associate with the siII or siIII mitochondrial haplogroups, respectively. To ask how polymorphism relates to Wolbachia infection status, we sequenced 1776 bp of mitochondrial DNA and 1029 bp of the X-linked per locus from 79 lines. The two southern populations were infected with wRi and exhibited significantly reduced mtDNA variation, while Wolbachia-uninfected siII flies from Tanzania and Kenya showed high levels of mtDNA polymorphism. These are the first known populations of D. simulans that do not exhibit reduced mtDNA variation. We observed no mitochondrial variation in the siIII haplogroup regardless of Wolbachia infection status, suggesting positive or background selection. These populations offer a unique opportunity to monitor evolutionary dynamics in ancestral populations that harbor multiple strains of Wolbachia.
The dermoscopic classification of atypical melanocytic naevi (Clark naevi) is useful to discriminate benign from malignant melanocytic lesions
2003-12-01

The dermoscopic classification of atypical naevi (Clark naevi) is useful to discriminate benign from malignant melanocytic lesions. The three-structure type and eccentric peripheral hyperpigmentation were significantly more frequently found in malignant than in benign melanocytic lesions. The knowledge of these two dermoscopic types should be helpful for the management of patients presenting with multiple melanocytic lesions.
On the Restricted and Combined Use of Rüdenberg’s Approximations in Molecular Orbital Theories of Hartree-Fock Type
2003-12-01

Rüdenberg’s well-known letter of 1951 entitled “On the Three- and Four-Center Integrals in Molecular Quantum Mechanics” explicitly presents two approximation formulas for four-center repulsion integrals, only. When applied to some types of three-center repulsion integrals, however, these two recipes still imply considerable oversimplifications. Using both one-electron and two-electron routes of Rüdenberg’s truncated expansion, on the other hand, such shortcomings can be avoided strictly. Starting from four simple “Unrestricted and Combined” (U&amp;C) approximation schemes introduced elsewhere, an improved “Restricted and Combined” (R&amp;C) approximation picture for Fock-matrix elements now will be outlined, which does not tolerate any unnecessary oversimplifications. Although the simplicity of the U&amp;C scheme is lost in this case, R&amp;C-approximated Fock-matrix elements still can be constructed from one- and two-center integrals alone in an effective way. Moreover, due to their dependence on a single geometric parameter, all types of two-center integrals can be calculated in advance for about one hundred fixed interatomic distances at the desired level of sophistication and stored once and for all. A cubic spline algorithm may be taken to interpolate the actual integral value from each precomputed list.
A Time-symmetric Hubble-like Law: Light Rays Grazing Randomly Moving Galaxies Show Distance-Proportional Redshift
2003-12-01

A new class of dissipative structures is proposed that live in real space rather than phase space. A light ray passing through a soup of randomly moving gravitating masses is a case in point. It suffers a “dynamic path elongation” since the random pushes and pulls have a greater probability of increasing than decreasing its path length. Time reversal then re-shrinks the path in question in a conspirational manner, while a close-by nonselected path gets expanded. This is a new statistical-mechanics phenomenon. The latter at the same time qualitatively reproduces the well-known Hubble phenomenon of distance-proportional light-path expansion in the cosmos. A preliminary quantitative estimate, based on the Birkinshaw equation with an assumed bias factor of three, is also presented.
Effects of Exercise Training on Quality of Life, Psychological Well-Being, Immune Status, and Cardiopulmonary Fitness in an HIV-1 Positive Population
2003-12-01

The present study was designed to examine the effects of a 16-week exercise intervention on several aspects of psychological and physical well-being in a sample of HIV-1 positive individuals. An exercise group ( n = 19) was compared with a control group ( n = 14) prior to and following the intervention on several outcome variables, including health related quality of life, psychological well-being (depression, anxiety, global symptoms), immune parameters, and cardiopulmonary parameters. The exercise group experienced a significant improvement in cardiopulmonary fitness, and health related quality of life improved significantly in that group relative to the control group. Psychological well-being improved similarly in both groups, however, while immune indices did not change in either group. Consistent with earlier studies, it is suggested that a moderate exercise intervention enhanced the health related quality of life in HIV-1 positive individuals.
Potential Role of Tetrahydrobiopterin in the Treatment of Maternal Phenylketonuria
2003-12-01

Objective. To evaluate the clinical relevance of tetrahydrobiopterin (BH4) supplementation for pregnant women with phenylketonuria (PKU)/hyperphenylalaninemia (HPA) and the possibility of treating these patients with BH4 instead of a phenylalanine (Phe)-restricted diet. Methods. Genotyping was performed on 41 patients with PKU/HPA identified by newborn screening. Evaluating the genotype according to their BH4 responsiveness is published. Follow-up of 3 patients with mild PKU treated with BH4 is evaluated. Discussion of the transfer of these experiences to the possibility of treating mothers at risk for maternal PKU is presented. Results. In 41 patients with PKU/HPA, we found 17 (41%) bearing at least 1 allele with a mutation described as being responsive to BH4. In 8 of the patients, BH4 loading had been performed in the newborn period, in 6 of whom the test showed a clear decrease of blood Phe 4 and 8 hours after loading. One of the nonresponders was reinvestigated at 3 years of age, showing a clear response (genotype Y414C/R408W): BH4 supplementation resulted in a much higher Phe tolerance (500 instead of 250 mg/day) with blood Phe levels &amp;lt;200 μmol/L. Two children (genotype E390G/IVS10–11g&amp;gt;a and L48S/L48S, respectively) were treated with BH4 only (15–20 mg/kg body weight/day), one from birth, the other from 2 years of age. Blood Phe decreased from &amp;gt;800 μmol/L to a mean of 321.4 and 331.7 μmol/L, respectively (range: 141–718 μmol/L) under a normal diet (total observation time: 4 years). Development was normal with no adverse reactions. Conclusions. BH4 supplementation seems to be a promising alternative treatment in some patients with mild PKU. Because blood Phe levels in maternal PKU should be maintained at 120 to 360 μmol/L, clinical relevance may be even greater than for treatment of children with PKU/HPA. BH4 supplementation may also be combined with a Phe-restricted diet, allowing higher Phe intake and protecting mothers from high Phe blood peaks. However, additional studies are necessary to prove the safety and economy of such an alternative treatment in patients with PKU/HPA, especially during pregnancy.
Sorption/desorption kinetics of contaminants on mobile particles: Modeling and experimental evidence
2003-12-01

In this study the impact of sorption/desorption kinetics between organic contaminants and mobile particles suspended in subsurface water is analyzed. TCE migration through a granular activated carbon column is investigated at different transport velocities with lignite and activated carbon particles as mobile carriers. The measured breakthrough characteristics of TCE can be reproduced by a reactive transport model simulating sorption/desorption kinetics applying an intraparticle diffusion approach for mobile particles and the packed bed of granular activated carbon. Model predictions are based on independently measured physicochemical parameters, i.e., no calibration of TCE sorption/desorption is required. The close matches of experimental data to predicted data validate the exclusively process‐based model assumptions and indicate that this approach has large predictive capabilities. Extending these findings, a sensitivity study is presented in order to specify under which conditions sorption/desorption of contaminants in mobile particles has to be modeled as a kinetic process. It is found that sorption/desorption kinetics are of major importance for Damköhler numbers between 0.01 and 100.