gebhart/patrepeval huggingface dataset:
Origin of Murine B Cell Lineages (1993)

Until recently, the hematopoietic stem cells (HSC) that appear early in ontogeny were thought to constitute a homogeneous, self-replenishing population whose developmental potential remains constant throughout the life of the animal. Studies reviewed here, however, demonstrated clear differences in the developmental potential of fetal and adult progenitor populations (including FACS-sorted HSC). These studies, which chart the ability of various progenitor sources to reconstitute functionally distinct B cell populations, define three B cell lineages: B-1a cells (CD5 B cells), derived from progenitors that are present in fetal omentum and fetal liver but are largely absent from adult bone marrow; B-1b cells ("sister" population), derived from progenitors that are present in fetal omentum, fetal liver, and also in adult bone marrow; and conventional B cells, whose progenitors are missing from fetal omentum but are found in fetal liver and adult bone marrow. B-1a and B-1b cells share many properties, including self-replenishment and feedback regulation of development. These B cell studies, in conjunction with evidence for a similar developmental switch for T cells and erythrocytes, suggest that evolution has created a "layered" immune system in which successive progenitors (HSC) reach predominance during development and give rise to differentiated cells (B, T, etc) responsible for progressively more complex immune functions.
Targeted Skipping of Human Dystrophin Exons in Transgenic Mouse Model Systemically for Antisense Drug Development (2011)

Antisense therapy has recently been demonstrated with great potential for targeted exon skipping and restoration of dystrophin production in cultured muscle cells and in muscles of Duchenne Muscular Dystrophy (DMD) patients. Therapeutic values of exon skipping critically depend on efficacy of the drugs, antisense oligomers (AOs). However, no animal model has been established to test AO targeting human dystrophin exon in vivo systemically. In this study, we applied Vivo-Morpholino to the hDMD mouse, a transgenic model carrying the full-length human dystrophin gene, and achieved for the first time more than 70% efficiency of targeted human dystrophin exon skipping in vivo systemically. We also established a GFP-reporter myoblast culture to screen AOs targeting human dystrophin exon 50. Antisense efficiency for most AOs is consistent between the reporter cells, human myoblasts and in the hDMD mice in vivo. However, variation in efficiency was also clearly observed. A combination of in vitro cell culture and a Vivo-Morpholino based evaluation in vivo systemically in the hDMD mice therefore may represent a prudent approach for selecting AO drug and to meet the regulatory requirement.
Psychometric properties of an instrument for assessing the experience of patients treated with inhaled insulin: the Inhaled Insulin Treatment Questionnaire (IITQ) (2010)

IITQ subscales had acceptable reliability (alpha = 0.68-0.87, median 0.83) and test-retest correlations (intra-class correlation coefficient = 0.67-0.90, median 0.82); floor effects (0.2-2.8%) and ceiling effects (0-9.3%) were minimal. Reliabilities for inhaler performance measures were acceptable (alpha = 0.73-0.90, median 0.85); there were no floor effects (0.0%) and ceiling effects (4.9-39.0%) were moderate. There were several modest associations between IITQ scores and measures of health status. Diabetes worries were lower for participants who had better mental health (type 2) and for those with higher BMI; perceptions of insulin therapy were more favorable for participants who had better physical and mental health; treatment satisfaction was higher for patients who had lower BMI (type 2), lower A1c levels, and better physical health (type 2); treatment preference was higher for patients with lower BMI (type 2) and better mental health (type 1). CONCLUSIONS -: Preliminary findings suggest that the IITQ is a comprehensive, reliable measure of the experience of patients treated with inhaled insulin.
MMM: a sequence-to-structure alignment protocol (2006)

Abstract Motivation: Accurate alignment of a target sequence to a template structure continues to be a bottleneck in producing good quality comparative protein structure models. Results: Multiple Mapping Method (MMM) is a comparative protein structure modeling server with an emphasis on a novel alignment optimization protocol. MMM takes inputs from five profile-to-profile based alignment methods. The alternatively aligned regions from the input alignment set are combined according to their fit in the structural environment of the template structure. The resulting, optimally spliced MMM alignment is used as input to an automated comparative modeling module to produce a full atom model. Availability: The MMM server is freely accessible at Contact: andras@fiserlab.org
Signaling to NF-κB (2004)

The transcription factor NF-kappaB has been the focus of intense investigation for nearly two decades. Over this period, considerable progress has been made in determining the function and regulation of NF-kappaB, although there are nuances in this important signaling pathway that still remain to be understood. The challenge now is to reconcile the regulatory complexity in this pathway with the complexity of responses in which NF-kappaB family members play important roles. In this review, we provide an overview of established NF-kappaB signaling pathways with focus on the current state of research into the mechanisms that regulate IKK activation and NF-kappaB transcriptional activity.
Stereospecificity of horseradish peroxidase (2004)

We report here on the stereospecificity observed in the action of horseradish peroxidase (HRPC) on monophenol and diphenol substrates. Several enantiomers of monophenols and o-diphenols were assayed: L-tyrosinol, D-tyrosinol, L-tyrosine, DL-tyrosine, D-tyrosine, L-dopa, DL-dopa, D-dopa, L-alpha-methyldopa, DL-alpha-methyldopa, DL-adrenaline, D-adrenaline, L-isoproterenol, DL-isoproterenol and D-isoproterenol. The electronic density at the carbon atoms in the C-1 and C-2 positions of the benzene ring were determined by NMR assays (delta1 and delta2). This value is related to the nucleophilic power of the oxygen atom of the hydroxyl groups and to its oxidation-reduction capacity. The spatial orientation of the ring substituents resulted in lower Km values for L- than for D-isomers. The kcat values for substrates capable of saturating the enzyme were lower for D- than for L-isomers, although both have the same delta1 and delta2 NMR values for carbons C-1 and C-2, and therefore the same oxidation-reduction potential. In the case of substrates that cannot saturate the enzyme, the values of the binding constant for compound II (an intermediate in the catalytic cycle) followed the order: L-isomer>DL-isomer>D-isomer. Therefore, horseradish peroxidase showed stereospecificity in its affinity toward its substrates (K m) and in their transformation reaction rates (k cat).
Measurement of thermal conductivity of bovine cortical bone (2000)

The thermal conductivity of cortical bone was characterized experimentally. Specimens were taken from the mid-diaphysis of bovine femora, and the rate of heat transfer was measured in three orthogonal directions. The conductivity was found to be 0.58+/-0.018 W/mK in the longitudinal direction, 0.53+/-0.030 W/mK in the circumferential direction, and 0.54+/-0.020 W/mK in the radial direction. Because the directional differences are small, it is concluded that bovine cortical bone can be treated as thermally isotropic.
Evaluating Formation and Growth Mechanisms of Silica Particles Using Fluorescence Anisotropy Decay Analysis (2004)

At present, there is no direct experimental evidence that primary silica particles, which exist only transiently for a few seconds during the Stöber silica synthesis, can be stable in aqueous solutions. In the present work, we show that primary silica particles are formed spontaneously after the dissolution of diglycerylsilane (DGS) in aqueous solutions and remain stable for prolonged periods of time. By using time-resolved fluorescence anisotropy (TRFA), we demonstrate that this unique property of DGS is ascribed to the slow kinetics of silica particle growth in diluted sols at pH approximately 9.0. The anisotropy decay of the cationic dye rhodamine 6G (R6G), which strongly adsorbs to silica oligomers and nanoparticles in DGS sols, could be fit to three components: a fast (picosecond) scale component associated with free R6G, a slower (nanosecond) rotational component associated with R6G bound to primary silica particles, and a residual (nondecaying) anisotropy component associated with R6G that was bound to secondary or larger particles that were unable to rotate on the time scale of the R6G emission lifetime (4 ns). The data show that, under conditions where fast hydrolysis is obtained, the initial size of the nuclei depends on the silica concentration, with larger nuclei being present in more concentrated sols, while the rate of growth of primary particles depends on both silica concentration and solution pH. At low silica concentrations and high pHs, it was possible to observe the growth of stable, nonaggregating primary silica particles by a mechanism involving rapid nucleation followed by monomer addition. The presence of stable primary particles was confirmed by atomic force microscopy (AFM) imaging. At higher silica concentrations and lower pHs, there was an increase in the initial size of the nuclei formed, which subsequently grew to a larger radius (> 4.5 nm) or aggregated with time, and in such cases, nucleation and aggregation occurred simultaneously in the early stage of silica formation. The data clearly show the power of time-resolved fluorescence anisotropy decay measurements for probing the growth of silica colloids and show that this method is useful for elucidating the mechanism of particle formation and growth in situ.
Reduced expression of CD20 antigen as a characteristic marker for chronic lymphocytic leukemia (1992)

The surface antigens expressed by the cells of chronic lymphocytic leukemia (CLL) are well known. Most CLL are monoclonal B-cell lymphoproliferative disorders characterized by the coexpression of B-cell antigens and CD5, an antigen present predominantly on T cells. Very little attention, however, has been paid to the quantitative characteristics of the expression of B-cell antigens in CLL. In this study, we used flow cytometry to analyze the expression of CD20, a well-known B-cell-associated antigen, in lymphocytes from 42 cases of CLL and its tissue counterpart, small lymphocytic lymphoma (SLL), and compared the results with results obtained from the analysis of 21 follicular lymphomas, 20 hyperplastic reactive nodes, and 26 samples of normal peripheral blood. The intensity of CD20 expression in the CLL/SLL cells was significantly lower than that of B cells in the other categories. This antigen expression abnormality does not appear to be a universal phenomenon in CLL/SLL, since CD19, another pan-B antigen, was expressed in CLL/SLL at levels higher than those in follicular lymphomas and comparable to those in reactive lymph nodes. These results indicate that the low CD20 expression can be used as a marker for CLL/SLL. The few cases exhibiting intense CD20 expression may represent a biologically different disease. CLL/SLL cells faintly expressing CD20 also show concomitant low CD5 expression in a manner not observed in normal CD5-expressing B cells.
The Concept of Weaning: Definitions and Their Implications (1996)

"Weaning" is usually said to refer to the entire process during which the infant changes from full dependence on breast milk to complete independence from it. However, "wean" is sometimes used to refer to provision of an "educational diet" during the first six months when exclusive breastfeeding is the ideal; to complementary feeding; to replacement of breastmilk; or to the cessation of breastfeeding. The processes involved are illustrated by a graph that theoretically compares the infant's nutritional needs with the proportion of those needs that can come from breastmilk under ideal circumstances. The development of consistent, relevant research, policies and programs on young child feeding may be particularly hindered by the failure to discriminate between complementation and replacement.
Effects of the D-1 Agonist SKF-38393 Combined With Haloperidol in Schizophrenic Patients (1990)

<h3>To the Editor.—</h3> The original dopamine (DA) hypothesis of schizophrenia suggested that D-2 receptor densities are augmented in subcortical brain areas and that the therapeutic effects of antipsychotic drugs are mediated by the antidopaminergic properties of these drugs. However, the notion that augmented dopaminergic activity is a consistent and pervasive phenomenon in schizophrenic patients is probably too simplistic. More recent elaboration of the DA hypothesis suggests that, depending on the brain area, dopaminergic activity could be increased or decreased.<sup>1</sup>In fact, clinical observations attribute some schizophrenic symptoms to frontal cortical dopaminergic deficits, and cerebral blood flow studies in schizophrenic patients indicate that frontal DA activity is reduced rather than augmented.<sup>2</sup> Animal experiments support the notion that reduced dopaminergic activity in cortical brain regions can coexist with, or even be the cause of, increased dopaminergic activity in subcortical areas. Lesions of dopaminergic innervation of the medial prefrontal cortex
Packaging capacity and stability of human adenovirus type 5 vectors (1993)

Adenovirus vectors are extensively used for high-level expression of proteins in mammalian cells and are receiving increasing attention for their potential use as live recombinant vaccines and as transducing viruses for use in gene therapy. Although it is commonly argued that one of the chief advantages of adenovirus vectors is their relative stability, this has not been thoroughly investigated. To examine the genetic stability of adenovirus type 5 vectors and in particular to examine the relationship between genetic stability and genome size, adenovirus vectors were constructed with inserts of 4.88 (herpes simplex virus type 1 gB), 4.10 (herpes simplex virus type 1 gB), or 3.82 (LacZ) kb combined with a 1.88-kb E3 deletion or with a newly generated 2.69-kb E3 deletion. The net excess of DNA over the wild-type (wt) genome size ranged from 1.13 to 3.00 kb or 3.1 to 8.3%. Analysis of these vectors during serial passage in tissue culture revealed that when the size exceeded 105% of the wt genome length by approximately 1.2 kb (4.88-kb insert combined with a 1.88-kb deletion), the resulting vector grew very poorly and underwent rapid rearrangement, resulting in loss of the insert after only a few passages. In contrast, vectors with inserts resulting in viral DNA close to or less than a net genome size of 105% of that of the wt grew well and were relatively stable. In general, viruses with genomes only slightly above 105% of that of the wt were unstable and the rapidity with which rearrangement occurred correlated with the size of the insert. These findings suggest that there is a relatively tight constraint on the amount of DNA which can be packaged into virions and that exceeding the limit results in a sharply decreased rate of virus growth. The resultant strong selection for variants which have undergone rearrangement, generating smaller genomes, is manifested as genetic instability of the virus population.
Tumor Cell Cytotoxicity of a Novel Metal Chelator (1998)

We have synthesized a novel six-coordinate metal chelator from the triamine cis-1,3,5-triaminocyclohexane by the addition of a 2-pyridylmethyl pendant arm on each nitrogen, which we term tachpyr. The experiments described here were designed to explore whether this compound exhibits potential antitumor activity. When added to MBT2 or T24 cultured bladder cancer cells, tachpyr was profoundly cytotoxic, with an IC50 of approximately 4.6 micromol/L compared with 70 micromol/L for desferioxamine. To explore the mode of action of tachpyr, several metal complexes were prepared, including Fe(II), Ca(II), Mn(II), Mg(II), Cu(II), and Zn(II) tachpyr complexes. Of these, the Zn(II), Cu(II), and Fe(II) complexes were without toxic effect, whereas the Ca(II), Mn(II), and Mg(II) complexes remained cytotoxic. To further probe the role of Zn(II) and Cu(II) chelation in the cytotoxicity of tachpyr, sterically hindered tachpyr derivatives were prepared through N-alkylation of tachpyr. These derivatives were unable to strongly bind Fe(III) or Fe(II) but were able to bind Zn(II) and Cu(II). When added to cells, these sterically hindered tachpyr derivatives were nontoxic, consistent with a role of iron depletion in the cytotoxic mechanism of tachpyr. Further, the addition of tachpyr to proliferating cultures resulted in an early and selective inhibition of ferritin synthesis, an iron storage protein whose translation is critically dependent on intracellular iron pools. Taken together, these experiments suggest that tachpyr is a cytotoxic metal chelator that targets intracellular iron, and that the use of tachpyr in cancer therapy deserves further exploration.
Human Hypertension Caused by Mutations in WNK Kinases (2001)

Hypertension is a major public health problem of largely unknown cause. Here, we identify two genes causing pseudohypoaldosteronism type II, a Mendelian trait featuring hypertension, increased renal salt reabsorption, and impaired K+ and H+ excretion. Both genes encode members of the WNK family of serine-threonine kinases. Disease-causing mutations in WNK1 are large intronic deletions that increase WNK1 expression. The mutations in WNK4 are missense, which cluster in a short, highly conserved segment of the encoded protein. Both proteins localize to the distal nephron, a kidney segment involved in salt, K+, and pH homeostasis. WNK1 is cytoplasmic, whereas WNK4 localizes to tight junctions. The WNK kinases and their associated signaling pathway(s) may offer new targets for the development of antihypertensive drugs.
Determination of lead in microliter amounts of whole blood by stripping potentiometry (1994)

Abstract Lead in whole blood is determined using a commercial potentiometric stripping analyzer in combination with a portable personal computer and a new electrode design permitting rotation of the sample. A 70 μL blood sample is added to 200 μL distilled water contained in a disposable test tube. After mixing, 400 μL of a matrix‐modifying solution containing hydrochloric acid, mercury (II) ions, Triton X‐100, and bismuth (III) as an internal standard, is added to the sample which is then transferred to the sample holder. Lead amalgam is deposited on the glassy carbon electrode by means of a pulsed potential cycle for 3 minutes after which lead is reoxidized by means of a constant current. The complete electroanalytical procedure, including result evaluation by means of the internal standard, and graphical display is under computer control. For ca. every 15th sample, the instrument is recalibrated, if necessary, using two whole blood standards. The relative precision is ca. 10% and the detection limit 3.5 μg/L. The stripping potentiometry results agree well with the results obtained by inductively coupled plasma mass spectrometry in the analysis of whole blood from individuals occupationally exposed to lead and with the results obtained by graphite‐furnace atomic spectroscopy in the analysis of whole blood from 141 school children.
Effect of Anti-CD25 Antibody Daclizumab in the Inhibition of Inflammation and Stabilization of Disease Progression in Multiple Sclerosis (2009)

clinicaltrials.gov Identifier: NCT00001934.
Interaction of Cartilage Matrix Protein with Aggrecan (1996)

Cartilage matrix protein (CMP) is a trimeric protein present in many types of cartilage extracellular matrix. It has recently been purified under native conditions that allowed the proposal of a structural model (Hauser, N., and Paulsson, M. (1994) J. Biol. Chem. 269, 25747-25753). To examine the functional properties of CMP we studied its interaction with aggrecan within cartilage extracellular matrix. Aggrecan-enriched fractions were purified from bovine tracheal cartilage of different ages under nondenaturing and denaturing conditions, respectively, and characterized by a combination of biochemical methods and electron microscopy. The fractions contained a pool of CMP noncovalently associated with aggrecan as well as a pool of CMP that appears covalently cross-linked to the aggrecan core protein. Only about two thirds of the CMP subunits could be released even upon reduction under denaturing conditions. It appears that CMP is attached by a nonreducible covalent interaction of one of its subunits with the protein core. The amount of CMP strongly bound to aggrecan increases with age. Electron microscopy revealed interaction sites for CMP in the extended chondroitin-sulfate attachment domain E2. In old tissue five distinct binding sites for CMP were found while in young cartilage only three of these were occupied. The extent of decoration of E2 with CMP increases with age.
The Sand Rat Model for Disc Degeneration: Radiologic Characterization of Age-Related Changes (2002)

Radiographic signs of degeneration were evident by age 2 months; wedging, narrowing, irregular disc margins, and endplate calcification were the most common degenerative changes in older animals. These data show that the sand rat provides a reliable, useful model of spontaneous disc degeneration.
Dendritic Spines: Cellular Specializations Imparting Both Stability and Flexibility to Synaptic Function (1994)

Dendritic spines, the tiny protrusions that stud the surface of many neurons, are the location of over 90% of all excitatory synapses that occur in the CNS. Their small size has, in large part, made them refractory to conventional experimental approaches. Yet their widespread occurrence and likely involvement in learning and memory has motivated extensive efforts to obtain quantitative descriptions of spines in both steady state and dynamic onditions. Since the seminal mathematical analyses of D’Arcy Thompson (1992), the power of quantitatively establishing key parameters of structure has become recognized as a foundation of successful biological inquiry. For dendritic spines, highly precise determinations of structure and its variation are again proving to be essential for establishing a valid concept of function. The recent conjunction of high quality information about the structure, function, and theoretical implications of dendritic spines has, in fact, produced a flurry of