gebhart/patrepeval huggingface dataset:
PROGRESSION OF SIALADENITIS IN SJÖGREN'S SYNDROME (1993)

An analysis of progression of sialadenitis in patients with primary and secondary SS has been performed. For this purpose patients were prospectively followed and evaluated with respect to stimulated whole salivary secretion and morphology of labial salivary gland biopsies. Twenty-one patients with primary SS and 18 with secondary SS were followed for a mean of 39 +/- 20 months (range 11-112 months). During this observation period the lymphocytic infiltration in minor salivary glands, measured as focus score, increased in 14/21 (67%) patients with primary SS and in 14/18 (78%) patients with secondary SS. Altogether there was a statistically significant increase in focus score in both primary and secondary SS, but no reduction in salivary production. Consequently, no correlation between changes in focus score and stimulated salivary secretion was found in either primary or secondary SS.
[Thalidomide: an eclectic medication in dermatology]. (1990)

The authors review the indications for the use of thalidomide in dermatological conditions. They consider leprotic reaction, prurigo nodularis of Hyde, actinic prurigo, discoid lupus erythematosus, Weber-Christian panniculitis, recurrent mouth aphtosis, Behcet's syndrome, and pyoderma gangrenosum. The dramatic situation created by the use of thalidomide in the sixties not-withstanding, interest in its use is warranted within certain limits due to its wide therapeutic action.
Phenotypical stability of a human hepatoma cell line, HuH-7, in long-term culture with chemically defined medium. (1984)

A chemically defined medium containing selenium was further improved, and the improved medium showed excellent ability to support growth and colony formation of a human hepatoma cell line, HuH-7. The improved defined medium (designated as IS-RPMI) contained small amounts of unsaturated fatty acids, inorganic trace elements including selenium, and HEPES buffer. Many of these additions exert only a small individual effect on the growth of cells, but their cumulative effects were substantial. HuH-7 cells replicated continuously with a doubling time of 47-51 hr in IS-RPMI. A conditioned medium from a semiconfluent population increased the colony-forming ability of HuH-7 cells in IS-RPMI. The addition of insulin to the medium gave good colony growth, thus duplicating the effect of the conditioned medium. Although some alterations of morphological and growth characteristics of HuH-7 cells were observed, the differentiated liver functions, as revealed by production of plasma proteins including high levels of alpha 1-fetoprotein, were maintained for a period of more than 3 years and through 70 passages under the above culture conditions.
Selective retention of oxygen using chromatographic columns containing metal chelate polymers (1985)

Porous polymers containing various metal chelates bonded to nitrogen functionalities on the surface of the polymer have been synthesized and found to bind oxygen reversibly. The stationary phases containing [5,5'-(1,2-ethanediyldinitrilo)-bis(2,2,7-trimethyl-3-octanonato)]cobalt(II) were found to be the most suitable of the phases investigated for separating oxygen for argon, nitrogen, and carbon monoxide. At ambient temperatures, near 25 degrees C, the reversible interaction of molecular oxygen with the transition-metal complex bonded to the stationary phase results in a marked increase in the retention time of oxygen, relative to species that have similar retention times in columns that do not contain the metal chelate. The stationary phase can be used alone to achieve the separation of low molecular weight gases or in series with another column. The metal chelate stationary phase is selective for oxygen and little change in the retention time of oxygen is observed after hundreds of injections over a several-month period, indicating that no appreciable degradation of the stationary phase had taken place under these conditions.
VLSI Design of a High-Throughput Multi-Rate Decoder for Structured LDPC Codes (2005)

Despite recent advances in the microelectronics technology, the implementation of high-throughput decoders for LDPC codes remains a challenging task. This paper aims at summarising the top-down design flow of a decoder for a structured LDPC code compliant with the WWiSE proposal for WLAN. Starting from the system performance analysis with finite-precision arithmetic, a high-throughput architecture is presented as an enhancement of the state-of-the-art solutions, and its VLSI design detailed. The envisaged architecture is also very flexible as it supports several code rates with no significant hardware overhead. The overall decoder, synthesised on 0.18/spl mu/m standard cells CMOS technology, showed remarkable performances: small implementation loss (0.2dB down to BER=10/sup -8/), low latency (less than 6.0/spl mu/s), high useful throughput (up to 940 Mbps) and low complexity (about 375 Kgates).
Biochemical and Biophysical Characterization of Serotonin 5-HT2CReceptor Homodimers on the Plasma Membrane of Living Cells (2004)

While many studies have provided evidence of homodimerization and heterodimerization of G-protein-coupled receptors (GPCRs), few studies have used fluorescence resonance energy transfer (FRET) combined with confocal microscopy to visualize receptor dimerization on the plasma membrane, and there have been no reports demonstrating the expression of serotonin receptor dimers/oligomers on the plasma membrane of living cells. In the study presented here, biochemical and biophysical techniques were used to determine if 5-HT(2C) receptors exist as homodimers on the plasma membrane of living cells. Immunoprecipitation followed by Western blotting revealed the presence of immunoreactive bands the predicted size of 5-HT(2C) receptor monomers and homodimers that were detergent and cross-linker sensitive. Bioluminescence resonance energy transfer (BRET) was assessed in HEK293 cells expressing 5-HT(2C) receptors labeled with Renilla luciferase and yellow fluorescent protein. BRET levels were not altered by pretreatment with serotonin. Confocal microscopy provided direct visualization of FRET on the plasma membrane of live cells expressing 5-HT(2C) receptors labeled with cyan (donor) and yellow (acceptor) fluorescent proteins. FRET, assessed by acceptor photobleaching, was dependent on the donor/acceptor ratio and independent of acceptor expression levels, indicating that FRET resulted from receptor clustering and not from overexpression of randomly distributed receptors, providing evidence for GPCR dimers/oligomers in a clustered distribution on the plasma membrane. The results of this study suggest that 5-HT(2C) receptors exist as constitutive homodimers on the plasma membrane of living cells. In addition, a confocal-based FRET method for monitoring receptor dimerization directly on the plasma membrane of living cells is described.
Immuno-PET for tumor targeting. (2003)

Monoclonal antibodies are approved for use as diagnostics and therapeutics in a broad range of medical indications including transplantation, cardiology, inflammatory diseases, viral infection, and oncology. Each of these indications utilizes the specificity and avidity of monoclonal antibodies for
A unified hot carrier degradation model for integrated lateral and vertical nDMOS transistors (2004)

In this paper, the hot carrier degradation behavior of integrated lateral and vertical DMOS transistors is analyzed. It will be shown that a unified degradation model is applicable to both devices. In the LDMOS, two degradation mechanisms occur: the electron mobility decreases due to increased carrier scattering upon D/sub it/ formation; and hot-hole injection and trapping occurs in the drift region. It will be shown that the second mechanism is absent in the VDMOS. TCAD simulations are used to support the experimental findings.
GAA expansion size and age at onset of Friedreich’s ataxia (2003)

More than 95% of patients with Friedreich ataxia (FA) are homozygous for GAA trinucleotide repeat expansions within intron 1 of the FRDA gene located on chromosome 9q13.1 A clear relation between GAA expansion size and phenotype variability has been found, and the size of the smaller GAA expansion (GAA1 allele) is the major determining factor for the variability in age at onset and rate of disease progression.2-7⇓⇓⇓⇓⇓ Conversely, the role of the larger GAA expansion (GAA2 allele) in age at onset has not been well established. We have assessed the predictive value of GAA1 and GAA2 sizes in regard to age at onset of the disease.

We selected a group of 40 patients homozygous for GAA expansion on the first intron of the FRDA gene, which was determined as described previously.1 Age at onset was defined as the age at which the first neurologic symptom was …
A survey of diagnosis, management, and grading of chronic GVHD (2002)

Chronic GVHD (cGVHD) is a potentially devastating late complication of allogeneic stem cell transplantation. To better understand current diagnostic and treatment practices regarding this complication, we mailed a self-administered survey to 188 adult and pediatric transplantation programs. The survey collected data on experience with therapies for cGVHD and presented 6 vignettes to assess agreement about the diagnosis, clinical management, grading, and prognosis of patients with symptoms of cGVHD. Response rate to the survey was 51%. Of the respondents, 28% felt they had "great success" in treating patients with systemic corticosteroids, and 13% had similar success with cyclosporine or mycophenolate mofetil; less success and experience were reported with other agents. Respondents estimated an average 3-year, nonrelapse mortality of 16% (95% CI, 14%-19%) for patients assessed to have limited disease and 39% (95% CI, 36%-43%) for extensive disease. Analysis of responses to the 6 vignettes showed that agreement was greatest for supportive care issues, willingness to enroll patients in clinical trials, and use of systemic immunosuppression for symptomatic cGVHD. Less agreement was seen for diagnosis and management when cGVHD manifestations were atypical or less severe, the decision of whether to taper immunosuppression in the face of stable symptoms, and for assignment of mild, moderate, or severe cGVHD grades. Most respondents were willing to use systemic immunosuppression to treat symptoms that they believed to be caused by cGVHD, but differences of opinion about cGVHD diagnosis and disease activity resulted in significant practice variation. Low estimates of treatment success were noted and reflected an overall pessimism about the success of therapy for cGVHD. We conclude that studies defining appropriate diagnostic pathways, criteria for disease activity, and prognosis could help standardize management of cGVHD. There is an urgent need to develop and test new approaches to treat cGVHD.
Expression of major histocompatibility complex class I antigens in normal and transformed rat thyroid epithelial cell lines. (1987)

Recent evidence suggests that the expression of abnormally high amounts of major histocompatibility complex (MHC) class I molecules may be a feature of at least some kinds of transformed cells. To investigate this aspect of neoplastic transformation we studied the expression of MHC class I antigens in an experimental model of normal, tumor-derived, and virus-transformed thyroid epithelial cell lines. The expression of MHC class I antigens has been studied by means of several monoclonal antibodies directed against either monomorphic or polymorphic epitopes and quantified by flow cytometry. Class I specific mRNA transcripts have been also analyzed by Northern blot hybridization, using a mouse genomic H-2 DNA probe. Our results indicate a modulation of MHC class I expression associated with loss of the differentiated phenotype and with transformation of thyroid epithelial cell lines. Undifferentiated cells in fact show a small quantity of these antigens, because acquisition of a fully differentiated phenotype is associated with an increase in their expression. Cell lines derived from thyroid tumors show reduced expression of MHC class I antigens, as compared to differentiated cells. Conversely, cells transformed in vitro by a retrovirus carrying the v-raski oncogene exhibit an increase in these antigens in comparison to their normal differentiated counterparts. Cells infected with a mutant virus able to transform cells only at the permissive temperature of 33 degrees C show a similar increased expression. After a shift to the nonpermissive temperature of 39 degrees C, infected cells, even those losing the transformed phenotype retain the same increased amount of MHC class I antigens. Our data suggest that the modulation of MHC class I antigen expression is strongly associated with transformation in thyroid epithelial cells.
Exogenously Regulated Stem Cell-Mediated Gene Therapy for Bone Regeneration (2001)

Regulated expression of transgene production and function is of great importance for gene therapy. Such regulation can potentially be used to monitor and control complex biological processes. We report here a regulated stem cell-based system for controlling bone regeneration, utilizing genetically engineered mesenchymal stem cells (MSCs) harboring a tetracycline-regulated expression vector encoding the osteogenic growth factor human BMP-2. We show that doxycycline (a tetracycline analogue) is able to control hBMP-2 expression and thus control MSC osteogenic differentiation both in vitro and in vivo. Following in vivo transplantation of genetically engineered MSCs, doxycycline administration controlled both bone formation and bone regeneration. Moreover, our findings showed increased angiogenesis accompanied by bone formation whenever genetically engineered MSCs were induced to express hBMP-2 in vivo. Thus, our results demonstrate that regulated gene expression in mesenchymal stem cells can be used as a means to control bone healing.
Some Agronomic Factors Affecting N-Dimethyl-nitrosamine Content in Cigarette Smoke (1975)

Abstract ExperimentaI cigarettes from tobaccos varying in genotype, nitrogen nutrition, stalk position, suckering practice, and curing methods were used to examine the Ievels of N-dimethylnitrosamine (DMN) in smoke. Measurable amounts of DMN were found in all experimental samples, ranging from 1.7 to 115 ng per gram of tobacco burned. DMN content in smoke generally increased as rate of N fertilization increased. However, there were wide seasonal, cultural, and varietal effects. Burley-type tobacco produced a much higher level of DMN than the bright-type tobacco. DMN content in smoke was significantly and positively related to Ieaf total N, totaI alkaloids, nicotine, nornicotine, total volatile bases and nitrate N, but negatively related to reducing sugars. Reconstituted sheet tobaccos made with homogenized-leaf-curing samples produced much lower amounts of DMN than conventionally cured leaf. Additional information is needed to elucidate the primary leaf constituents that serve as precursors of DMN.
Coexistence of Ultra-Wideband Systems with IEEE-802.11a Wireless LANs (2004)

In this study we provide a physical layer based analysis of the coexistence issues of ultra-wideband (UWB) with other devices in the same spectrum. Specifically, we have focused on the UWB interference to and from devices using the wireless local area network (WLAN) standard IEEE 802.11a. Our results indicate that a UWB interferer operating at the peak allowable power density induces minimal interference into such WLAN devices in line-of sight (LOS) scenarios, even at close range. However, in the non-LOS (NLOS) case, a UWB interferer can severely affect the data-rate sustainable by 802.11a systems. Moreover, 802.11a interference into UWB systems is shown to reduce the signal-to-interference ratio (SIR) by as much as 36 dB when the interferer is within LOS of the UWB receiver.
Genetic factors that influence moenomycin production in streptomycetes (2010)

Moenomycin, a natural phosphoglycolipid product that has a long history of use in animal nutrition, is currently considered an attractive starting point for the development of novel antibiotics. We recently reconstituted the biosynthesis of this natural product in a heterologous host, Streptomyces lividans TK24, but production levels were too low to be useful. We have examined several other streptomycetes strains as hosts and have also explored the overexpression of two pleiotropic regulatory genes, afsS and relA, on moenomycin production. A moenomycin-resistant derivative of S. albus J1074 was found to give the highest titers of moenomycin, and production was improved by overexpressing relA. Partial duplication of the moe cluster 1 in S. ghanaensis also increased average moenomycin production. The results reported here suggest that rational manipulation of global regulators combined with increased moe gene dosage could be a useful technique for improvement of moenomycin biosynthesis.
C5a Receptor Activation (1999)

Hormones and sensory stimuli activate serpentine receptors, transmembrane switches that relay signals to heterotrimeric guanine nucleotide-binding proteins (G proteins). To understand the switch mechanism, we subjected 93 amino acids in transmembrane helices III, V, VI, and VII of the human chemoattractant C5a receptor to random saturation mutagenesis. A yeast selection identified 121 functioning mutant receptors, containing a total of 523 amino acid substitutions. Conserved hydrophobic residues are located on helix surfaces that face other helices in a modeled seven-helix bundle (Baldwin, J. M., Schertler, G. F., and Unger, V. M. (1997) J. Mol. Biol. 272, 144-164), whereas surfaces predicted to contact the surrounding lipid tolerate many substitutions. Our analysis identified 25 amino acid positions resistant to nonconservative substitutions. These appear to comprise two distinct components of the receptor switch, a surface at or near the extracellular membrane interface and a core cluster in the cytoplasmic half of the bundle. Twenty-one of the 121 mutant receptors exhibit constitutive activity. Amino acids substitutions in these activated receptors predominate in helices III and VI; other activating mutations truncate the receptor near the extracellular end of helix VI. These results identify key elements of a general mechanism for the serpentine receptor switch.
Photoacoustic tomography: fundamentals, advances and prospects (2011)

Optical microscopy has been contributing to the development of life science for more than three centuries. However, due to strong optical scattering in tissue, its in vivo imaging ability has been restricted to studies at superficial depths. Advances in photoacoustic tomography (PAT) now allow multiscale imaging at depths from sub-millimeter to several centimeters, with spatial resolutions from sub-micrometer to sub-millimeter. Because of this high scalability and its unique optical absorption contrast, PAT is capable of performing anatomical, functional, molecular and fluid-dynamic imaging at various system levels, and is playing an increasingly important role in fundamental biological research and clinical practice. This review discusses recent technical progress in PAT and presents corresponding applications. It ends with a discussion of several prospects and their technical challenges.
Stabilization of Femtosecond Lasers for Optical Frequency Metrology and Direct Optical to Radio Frequency Synthesis (2001)

We have actively stabilized the comb of frequencies from a mode-locked femtosecond laser using a Fabry-Perot reference cavity. This technique offers the ability to synthesize a comb of highly stable radio frequencies directly from optical transitions. The measured fractional frequency instability of the components of the frequency comb relative to the reference cavity was <5x10(-13) in 0.1 sec. The variation of the optical mode spacing versus frequency of the reference cavity was also directly measured using this technique.
Structural Model for the Interaction of a Designed Ankyrin Repeat Protein with the Human Epidermal Growth Factor Receptor 2 (2013)

Designed Ankyrin Repeat Proteins are a class of novel binding proteins that can be selected and evolved to bind to targets with high affinity and specificity. We are interested in the DARPin H10-2-G3, which has been evolved to bind with very high affinity to the human epidermal growth factor receptor 2 (HER2). HER2 is found to be over-expressed in 30% of breast cancers, and is the target for the FDA-approved therapeutic monoclonal antibodies trastuzumab and pertuzumab and small molecule tyrosine kinase inhibitors. Here, we use computational macromolecular docking, coupled with several interface metrics such as shape complementarity, interaction energy, and electrostatic complementarity, to model the structure of the complex between the DARPin H10-2-G3 and HER2. We analyzed the interface between the two proteins and then validated the structural model by showing that selected HER2 point mutations at the putative interface with H10-2-G3 reduce the affinity of binding up to 100-fold without affecting the binding of trastuzumab. Comparisons made with a subsequently solved X-ray crystal structure of the complex yielded a backbone atom root mean square deviation of 0.84-1.14 Ångstroms. The study presented here demonstrates the capability of the computational techniques of structural bioinformatics in generating useful structural models of protein-protein interactions.
Constitutively Active ALK2 Receptor Mutants Require Type II Receptor Cooperation (2013)

Constitutively activating mutations in receptor kinases recruit downstream effector pathways independently of upstream signaling, with consequences ranging from developmental syndromes to cancer. Classic fibrodysplasia ossificans progressiva (FOP) is a congenital syndrome resulting from highly conserved activating mutations of the glycine-serine-rich (GS) regulatory domain of ACVR1, encoding bone morphogenetic protein (BMP) type I receptor ALK2, which lead to inappropriate signaling and heterotopic ossification of soft tissues. It is unclear if constitutively active mutant ALK2 receptors (caALK2) can function independently of signaling complexes with type II receptors and ligands. We found that ablation of BmpRII and ActRIIa abrogated BMP ligand-mediated and caALK2-mediated signaling and transcription in cells and disrupted caALK2-induced heterotopic ossification in mice. Signaling via GS domain ALK2 mutants could be restored by the expression of either BMP type II receptor. The contribution of BMP type II receptors was independent of their ligand-binding or kinase function but was dependent upon an intact cytoplasmic domain. These data demonstrate that GS domain ALK2 mutants act independently of upstream signaling but may require a nonenzymatic scaffolding function provided by type II receptors to form functional, apparently ligand-independent signaling complexes. These findings define the minimal requirements for signaling of GS domain ALK2 mutants, with implications for the therapeutic targeting of their activity in disease.