gebhart/patrepeval huggingface dataset:
Analysis of multilayer radio frequency microcoils for nuclear magnetic resonance spectroscopy (2001)

Although its strength lies in its ability to determine chemical structure completely, nuclear magnetic resonance (NMR) spectroscopy is relatively insensitive compared to other analytical techniques. As a result, significant research has been directed at improving the overall sensitivity of NMR spectroscopy by optimizing radio-frequency (RF) coil design. To investigate volume- and mass-limited samples, RF microcoils have been examined extensively. These solenoidal wire coils take advantage of reduced coil diameter to improve the signal-to-noise ratio (SNR) of microcoils for constrained samples. To study the properties of a multilayer configuration, both theoretical and experimental solutions for conductor thicknesses above the skin depth at the frequency of operation. Experimental data for thicker conductors displays a reduction in SNR with increased layers, supporting the theoretical development. As indicated by analytical theory and as partially confirmed by experimentation, SNR improvements for multilayer microcoils may be realized only when the conductor thickness is on the order of the skin depth. However, the utilization and availability of skin-depth conductors in the fabrication of current microcoil designs are not trivial matters. To take advantage of the SNR benefits of a multilayer microcoil geometry, we suggest a new configuration called the scroll coil. This novel geometry offers additional flexibility in fabrication that may be of great benefit in high-resolution NMR spectroscopy, especially at very small coil dimensions.
Screening Mercury Levels in Fish with a Selective Fluorescent Chemosensor (2005)

Societal concerns over toxic mercury accumulation in humans from fish and other dietary and environmental sources provide motivation to develop new tools and tactics for mercury detection in a wide range of laboratory and field settings. Here we report the synthesis, properties, and application of a selective and sensitive small-molecule chemosensor for fluorescence screening of mercury levels in fish. Mercuryfluor-1 (MF1) is a water-soluble, fluorescein-based reagent that features excellent selectivity for Hg2+ over competing analytes and the largest turn-on fluorescence response to date (>170-fold increase) for reporting this heavy metal ion in aqueous solution. Combining this chemoselective Hg2+ probe with a microwave digestion protocol provides a facile method for assaying mercury levels in fish samples with mercury concentrations spanning 0.1 to 8 ppm, a range well matched with the United States Environmental Protection Agency (U.S. EPA) standard for the maximum safe level of mercury in edible fish (0.55 ppm).
Off-label use and reimbursement of contrast media in MR (1999)

Use of an approved contrast agent for a clinical purpose not contained in the package insert is not in violation of current U.S. Acts providing that it is in the course of routine medical practice, not part of an investigation into safety or effectiveness and not commercialized through advertising. The Food and Drug Administration does not have the authority to regulate the use of approved contrast media in any manner that radiologists believe, in their professional judgment, would best serve the patient. Moreover, the use of an approved contrast agent for a clinical purpose not explicitly contained in the labeling does not expose the radiologist to malpractice liability. Regarding reimbursement, there is no guarantee that any payer will reimburse a provider for use of a contrast agent outside of package insert indications. The best way to influence reimbursement is to provide the payer with detailed information prior to claim submission.
Monitoring Influenza Trends through Mining Social Media. (2009)

Analysis of Google Influenza-like-illness (ILI) search queries has shown a strongly correlated pattern with Center for Disease Control and Prevention seasonal ILI reporting data. Web and social media (WSM) provide another resource to detect increases in ILI. This paper evaluates trends in blog posts that discuss Influenza. The results of the analysis show Influenza-related blogging trends have a significant correlation with the beginning of US Fall 2008 flu season. We also identify WSM Influenza-related communities that share flu-postings which could broker or disseminate information in the case of a severe outbreak or Influenza epidemic.
Vaccines. (1999)

Extensive research with mice has shown that animals can be protected from or cured of Helicobacter infection by immunization. A therapeutic effect has also been demonstrated in ferrets. The possibility of developing a vaccine against H. pylori-associated diseases that will work in humans has been the stimulus for intense research activity. A major subset of lymphocytes involved in immunity against invading pathogens is the CD4+ T-lymphocytes, divided into Th1 and Th2 phenotypes. Th1 cells are involved in cell-mediated immunity and Th2 cells are involved in antibody formation, particularly IgA and IgG, which are most active at mucosal surfaces and thus most likely to be protective against bacteria trying to colonize that surface. H. pylori can exist for the life of its human host, despite the vigorous immune response that is mounted against it. Most infected humans have a Th1 response, which does not eradicate H. pylori. A Th2 response would logically be more effective. Experiments with mice deficient in the cytokines that drive the Th responses are confusing and indicate that a change in the balance of the Th1/Th2 response may have a therapeutic effect In the next 2-5 years, a number of anti-Helicobacter vaccines will be studied in humans and this will open up a completely new approach to the management of gastroduodenal diseases.
Phosphodiesterase 4-targeted treatments for autoimmune diseases (2013)

Advancements in phosphodiesterase (PDE)-targeted therapies have shown promise in recent years for treating patients with a variety of autoimmune diseases. This review summarizes the development of PDE4 inhibitors and the associated literature with a focus on treatments for autoimmune diseases. After the initial investigations of the prototypic PDE inhibitor, rolipram, more selective inhibitors targeting the PDE4 isozyme have been developed. With phase II and phase III clinical trials currently underway to evaluate the safety and efficacy of the latest generation of PDE4 inhibitors, namely apremilast, a new class of treatments may be around the corner for patients suffering from chronic, autoimmune diseases.
A. thaliana TRANSPARENT TESTA 1 is involved in seed coat development and defines the WIP subfamily of plant zinc finger proteins (2002)

Seeds of the Arabidopsis thaliana transparent testa 1 mutant (tt1) appear yellow, due to the lack of condensed tannin pigments in the seed coat. The TT1 gene was isolated by reverse genetics using an En-1 transposon mutagenized A. thaliana population. TT1 gene expression was detected in developing ovules and young seeds only, and the gene was shown to encode a nuclear protein. Mutant seeds displayed altered morphology of the seed endothelium in which brown tannin pigments accumulate in wild-type plants, indicating that TT1 is involved in the differentiation of this cell layer. When overexpressed in transgenic A. thaliana plants, TT1 caused aberrant development and organ morphology. The protein contains a novel combination of two TFIIIA-type zinc finger motifs. Closely related motifs were detected in a number of putative proteins deduced from plant genomic and EST sequences. The new protein domain containing this type of zinc finger motifs was designated WIP, according to three strictly conserved amino acid residues. Our data indicate the existence of a small gene family in A. thaliana which is defined by the occurrence of the WIP domain. WIP genes may play important roles in regulating developmental processes, including the control of endothelium differentiation.
Peak height variations in automated sequencing of PCR products using Taq dye-terminator chemistry. (1995)

Direct sequencing of PCR products using Taq DNA polymerase with dye-labeled dideoxy chain terminators results in traces with uneven peaks. The peak height variations reflect the disproportionate rate of incorporation of deoxynucleotides vs. their analogs, a phenomenon that is highly dependent on the neighboring DNA sequence. Such peak height variations make it difficult to call bases correctly or to interpret whether or not a polymorphism is present. We have systematically examined pairs of sequence-tagged sites that vary at only one nucleotide to determine how a single base change will affect the peak heights of neighboring bases. We have found that the peak height of a particular base can often be predicted from the knowledge of just one or two nucleotides 5'- to the base in question. We have also observed several artifacts that occur consistently in the sequencing traces. These artifacts can be misinterpreted as polymorphisms or can obscure the real peak at that site. The empirically derived trends presented in this report can be utilized profitably when one is editing sequence data or examining them for polymorphisms and mutations.
A framework for uplink power control in cellular radio systems (1995)

In cellular wireless communication systems, transmitted power is regulated to provide each user an acceptable connection by limiting the interference caused by other users. Several models have been considered including: (1) fixed base station assignment where the assignment of users to base stations is fixed, (2) minimum power assignment where a user is iteratively assigned to the base station at which its signal to interference ratio is highest, and (3) diversity reception where a user's signal is combined from several or perhaps all base stations. For the above models, the uplink power control problem can be reduced to finding a vector p of users' transmitter powers satisfying p/spl ges/I(p) where the jth constraint p/sub j//spl ges/I/sub j/(p) describes the interference that user j must overcome to achieve an acceptable connection. This work unifies results found for these systems by identifying common properties of the interference constraints. It is also shown that systems in which transmitter powers are subject to maximum power limitations share these common properties. These properties permit a general proof of the synchronous and totally asynchronous convergence of the iteration p(t+1)=I(p(t)) to a unique fixed point at which total transmitted power is minimized.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Maturation and function of cystic fibrosis transmembrane conductance regulator variants bearing mutations in putative nucleotide-binding domains 1 and 2. (1991)

One feature of the mutations thus far found to be associated with the disease cystic fibrosis (CF) is that many of them are clustered within the first nucleotide-binding domain (NBD) of the CF transmembrane conductance regulator (CFTR). We sought to discover the molecular basis for this clustering by introducing into the two NBDs of CFTR mutations either mimicking amino acid changes associated with CF or altering residues within highly conserved motifs. Synthesis and maturation of the mutant CFTR were studied by transient expression in COS cells. The ability of the altered proteins to generate cyclic AMP-stimulated anion efflux was assessed by using 6-methoxy-N-(sulfopropyl) quinolinium (SPQ) fluorescence measurements in HeLa cells expressing mutated plasmids. The results show that (i) all CF-associated mutants, with one exception, lack functional activity as measured in the SPQ assay, (ii) mutations in NBD1 are more sensitive to the effects of the same amino acid change than are the corresponding mutations in NBD2, (iii) cells transfected with plasmids bearing CF-associated mutations commonly but not exclusively lack mature CFTR, (iv) NBD mutants lacking mature CFTR fail to activate Cl- channels, and (v) the glycosylation of CFTR, per se, is not required for CFTR function. We reason that the structure of NBD1 itself or of the surrounding domains renders it particularly sensitive to mutational changes. As a result, most NBD1 mutants, but only a few NBD2 mutants, fail to mature or lack functional activity. These findings are consistent with the observed uneven distribution of CFTR missense mutations between NBD1 and NBD2 of CF patients.
Molecular Cloning and Expression of a Chloride Ion Channel of Cell Nuclei (1997)

Ion channels are known to be present on the plasma membrane of virtually all cells and have been found on the membranes of various intracellular organelles. However, until recently they were believed not to occur at the nuclear membrane. In this study we describe the molecular cloning and characterization of a nuclear ion channel protein, designated nuclear chloride channel-27 (NCC27), from the human myelomonocytic cell line, U937. NCC27 is a novel chloride ion channel protein that was found to localize principally to the cell nucleus. Its only known homologue is a bovine chloride ion channel protein (p64) believed to localize to internal organelles. NCC27 therefore represents the first human member of a new class of organellar chloride ion channel proteins.
Antigenic and virulence properties of Pasteurella haemolytica leukotoxin mutants (1995)

Antigenic properties of two mutants of Pasteurella haemolytica, strains 59B0071 and 59B0072, that do not produce detectable leukotoxin were investigated. Western blot (immunoblot) analysis with a number of polyclonal sera from animals recovering from pasteurellosis revealed that both mutants secreted a variety of antigens that were also present in cultures of several wild-type strains. These antigens ranged from about 100 to 15 kDa. Mutant strain 59B0071 was found to be totally deficient in leukotoxin, as judged not only by Western blotting but also by cytotoxicity assays with bovine lymphoma (BL-3) cells or bovine polymorphonuclear cells as targets. The mutant strain 59B0071 had normal levels of a secreted sialylglycoprotease, however. When strains were tested for virulence in goat and cattle challenge experiments, a reduction in mortality and lung lesions was observed with the mutant 59B0071 in comparison with results obtained with wild-type strains. These results are consistent with an important role for leukotoxin in P. haemolytica virulence and suggest that leukotoxin-negative mutants may be useful tools in the investigation of other virulence properties involved in P. haemolytica infections.
The dynamics of acentric chromosomes in cancer cells revealed by GFP-based chromosome labeling strategies (2000)

Autonomous replicons, such as viral episomes and oncogene containing double minute chromosomes (DMs), lack centromeres and consequently should be lost rapidly when the nuclear membrane breaks down at mitosis. Surprisingly, they are not. This raises the important question of the mechanisms that enable their efficient transmission to daughter cells. We review recent developments in GFP-based chromosome labeling strategies that enable real time analyses using high resolution light microscopy to provide insights into this issue. The results reveal that episomes and DMs both adhere to host chromosomes, a process referred to as "chromosome tethering". Such association enables acentric molecules to use the chromosomal centromere in trans, thereby achieving efficient transmission to daughter cells. This unique mechanism of mitotic segregation also raises the possibility of developing a new class of anti-cancer drugs that work by selectively eliminating growth enhancing genes from cancer cells. J. Cell. Biochem. Suppl. 35:107-114, 2000.
The role of neuromodulation in the management of urinary urge incontinence (2003)

Sacral nerve stimulation is becoming the standard of care for refractory overactive bladder and retention problems. The potential benefit of neuromodulation should be included in female urology and gynaecology training programmes.
VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown (2009)

Breakdown of the blood-brain barrier (BBB) is an early and significant event in CNS inflammation. Astrocyte-derived VEGF-A has been implicated in this response, but the underlying mechanisms remain unresolved. Here, we identify the endothelial transmembrane tight junction proteins claudin-5 (CLN-5) and occludin (OCLN) as targets of VEGF-A action. Down-regulation of CLN-5 and OCLN accompanied up-regulation of VEGF-A and correlated with BBB breakdown in experimental autoimmune encephalomyelitis, an animal model of CNS inflammatory disease. In cultures of brain microvascular endothelial cells, VEGF-A specifically down-regulated CLN-5 and OCLN protein and mRNA. In mouse cerebral cortex, microinjection of VEGF-A disrupted CLN-5 and OCLN and induced loss of barrier function. Importantly, functional studies revealed that expression of recombinant CLN-5 protected brain microvascular endothelial cell cultures from a VEGF-induced increase in paracellular permeability, whereas recombinant OCLN expressed under the same promoter was not protective. Previous studies have shown CLN-5 to be a key determinant of trans-endothelial resistance at the BBB. Our findings suggest that its down-regulation by VEGF-A constitutes a significant mechanism in BBB breakdown.
Microcirculatory disturbances during the early phase following experimental spinal cord trauma in the rat. (1978)

The early (primary) lesion of the microvasculature and neurons in the gray matter of the rat become mainfest within 0-3 min, long before the development of secondary ischemic-anoxic changes. The central hemorrhagic necrosis of the gray matter, induced by the impact injury, seems to depend primarily on theseverity of trauma. However, since the lesion is limited to the gray matter of one or two segments, these primary changes are not responsible for the irreversible transverse lesion. Additionally, the experimental cord injury in the rat demonstrates that secondary vascular changes (i.e., the pathological permeability of vessels in the white matter) produce a progressive edema that spreads into the necrotic zone and leads to definite transverse lesion. Not least of all, the increased pressure of the spinal tissue may promote the self-destructive process leading to irreversible damage to white matter.
T cell senescence and contraction of T cell repertoire diversity in patients with chronic obstructive pulmonary disease (2009)

Pathogenetic mechanisms leading to chronic obstructive pulmonary disease (COPD) remain poorly understood. Because clonogenic T cells (CD4(+)CD28(null)) were shown to be increased in autoimmune diseases we hypothesized that CD4(+)CD28(null) T cells play a role in COPD. Here we describe that enhanced presence of CD4(+)CD28(null) cells is associated with impaired lung function. Sixty-four patients and controls were included. T cell phenotype was analysed using flow cytometry. Enzyme-linked immunosorbent assays were utilized to determine cytokines. Statistical evaluations were performed using non-parametric group comparisons and correlations. A logistic regression model was used to determine predictive values of CD4(+)CD28(null) in the diagnosis of COPD. Populations of CD4(+) T cells lacking surface co-stimulatory CD28 were enlarged significantly in evaluated patients when compared with controls. Natural killer (NK)-like T cell receptors (CD94, 158) and intracellular perforin, granzyme B were increased in CD4(+)CD28(null) cells. Cytokine production after triggering of peripheral blood mononuclear cells (PBMCs) was elevated in patients at early disease stages. Receiver operating characteristic curve plotting revealed that presence of CD4(+)CD28(null) T cells has a diagnostic value. These CD4(+)CD28(null) T cells show increased expression of NK-like T cell receptors (CD94, 158) and intracellular perforin and granzyme B. Furthermore, triggering of PBMCs obtained from patients with mild COPD led to increased interferon-gamma and tumour necrosis factor-alpha production in vitro compared with controls. Our finding of increased CD4(+)CD28(null) T cells in COPD indicates that chronic antigen exposure, e.g. through contents of smoke, leads to loss of CD28 and up-regulation of NK cell receptors expression on T cells in susceptible patients.
Home literacy experiences of preschoolers who use AAC systems and of their nondisabled peers (1993)

A survey was employed to compare the home literacy experiences of physically disabled preschoolers who use augmentative and alternative communication (AAC) systems to the experiences of their nondisabled (ND) peers. Questionnaires were completed by 15 parents of children in each group. Results of the survey indicated that the general reading and writing environments in the households of the two groups were similar: there were available a range of literacy materials and regular models of others reading and writing. Although both groups of children were reported to be interested in literacy activities, the children in the AAC group had less opportunity to use printed materials or to participate in writing/drawing activities. When engaged in story reading activities, the children in the AAC group seemed to be less involved in initiating and asking questions about the text than the children in the ND group. Parental priorities for their children differed somewhat between the two groups. The parents in the AAC group gave highest priority to communication and then to physical needs such as mobility and feeding. The parents of the ND group gave highest priority to communication and making friends, and then to literacy activities. Results of the study are discussed in light of the literature, and directions for future research are suggested.
Allogeneic HLA-A*02–Restricted WT1-Specific T Cells from Mismatched Donors Are Highly Reactive but Show Off-Target Promiscuity (2011)

T cells recognizing tumor-associated Ags such as Wilms tumor protein (WT1) are thought to exert potent antitumor reactivity. However, no consistent high-avidity T cell responses have been demonstrated in vaccination studies with WT1 as target in cancer immunotherapy. The aim of this study was to investigate the possible role of negative thymic selection on the avidity and specificity of T cells directed against self-antigens. T cell clones directed against the HLA-A*0201-binding WT1(126-134) peptide were generated from both HLA-A*02-positive (self-HLA-restricted) and HLA-A*02-negative [nonself (allogeneic) HLA [allo-HLA]-restricted] individuals by direct ex vivo isolation using tetramers or after in vitro priming and selection. The functional avidity and specificity of these T cell clones was analyzed in-depth. Self-HLA-restricted WT1-specific clones only recognized WT1(126-134) with low avidities. In contrast, allo-HLA-restricted WT1 clones exhibited profound functional reactivity against a multitude of HLA-A*02-positive targets, even in the absence of exogenously loaded WT1 peptide, indicative of Ag-binding promiscuity. To characterize this potential promiscuity, reactivity of the T cell clones against 400 randomly selected HLA-A*0201-binding peptides was investigated. The self-HLA-restricted WT1-specific T cell clones only recognized the WT1 peptide. In contrast, the allo-HLA-restricted WT1-reactive clones recognized besides WT1 various other HLA-A*0201-binding peptides. In conclusion, allogeneic HLA-A*02-restricted WT1-specific T cells isolated from mismatched donors may be more tumor-reactive than their autologous counterparts but can show specific off-target promiscuity of potential clinical importance. As a result of this, administration of WT1-specific T cells generated from HLA-mismatched donors should be performed with appropriate precautions against potential off-target effects.