gebhart/patrepeval huggingface dataset:
Multiple antioxidants in the prevention and treatment of neurodegenerative disease: analysis of biologic rationale (1999)

Parkinson's disease and Alzheimer's disease are major progressive neurologic disorders, the risk of which increases with advancing age (65 years and over). In familial cases, however, early onset of disease (35-65 years) is observed. In spite of extensive basic and chemical research on Parkinson's disease and Alzheimer's disease, no preventive or long-term effective treatment strategies are available. The analysis of existing literature suggests that oxidative stress is a major intermediary risk factor for the action of diverse groups of neurotoxins that are involved in these neurodegenerative diseases. In this review, it is proposed that the epigenetic components (mitochondria, other organelles, membranes, protein modification) rather than nuclear genes of neurons are the primary targets for the action of neurotoxins, including free radicals. In addition, a scientific rationale for using multiple antioxidants in clinical trials for the prevention of Parkinson's disease and Alzheimer's disease among high-risk populations, and as an adjunct to standard therapy in the treatment of these diseases is presented.
Comparison of Plasma Concentrations of Aerosolized Pentamidine in Nonventilated and Ventilated Patients with Pneumocystosis (1989)

Pentamidine concentrations were determined in plasma after a single aerosolization of 4 mg/kg pentamidine base on 18 patients breathing spontaneously (Group I) and in eight patients receiving mechanical ventilation (Group II). All the patients had documented pneumocystosis. Large interindividual variations in concentrations appeared, especially in Group I. Low concentrations were observed in Group I: Cmax = 65.6 +/- 9.4 micrograms/L (mean +/- SEM), contrasting with high levels in Group II: Cmax = 215.8 +/- 49.8 micrograms/L (mean +/- SEM). Consequently, the mean area under the curve from zero to 4 h was 2.6-fold higher in Group II than in Group I. These findings underline the risk of dose-related pentamidine toxicity in ventilated patients treated with aerosolized pentamidine and the interest of plasma pentamidine monitoring.
Intravital Microscopy of the Peripheral Lymph Node Microcirculation in Mice (1996)

The present study develops a new intravital microscopy model for in vivo visualization of leukocyte interactions with microvessels in murine LN. The preparation permitted an analysis of biophysical and molecular mechanisms of leukocyte adhesion to high endothelial cells. The data support the concept that L-selectin and PNAd are the predominant receptor/ligand pair responsible for lymphocyte rolling in HEV. The model will be useful for high-resolution analysis of intra- and extravascular events in living LN.
phnE and glpT Genes Enhance Utilization of Organophosphates in Escherichia coli K-12 (1998)

Wild-type Escherichia coli K-12 strain JA221 grows poorly on low concentrations (< or = 1 mM) of diisopropyl fluorophosphate and its hydrolysis product, diisopropyl phosphate (DIPP), as sole phosphorus sources. Spontaneous organophosphate utilization (OPU) mutants were isolated that efficiently utilized these alternate sources of phosphate. A genomic library was constructed from one such OPU mutant, and two genes were isolated that conferred the OPU phenotype to strain JA221 upon transformation. These genes were identified as phnE and glpT. The original OPU mutation represented phnE gene activation and corresponded to the same 8-bp unit deletion from the cryptic wild-type E. coli K-12 phnE gene that has been shown previously to result in phnE activation. In comparison, sequence analysis revealed that the observed OPU phenotype conferred by the glpT gene was not the result of a mutation. PCR clones of glpT from both the mutant and the wild type were found to confer the OPU phenotype to JA221 when they were present on the high-copy-number pUC19 plasmid but not when they were present on the low-copy-number pWSK29 plasmid. This suggests that the OPU phenotype associated with the glpT gene is the result of amplification and overproduction of the glpT gene product. Both the active phnE and multicopy glpT genes facilitated effective metabolism of low concentrations of DIPP, whereas only the active phnE gene could confer the ability to break down a chromogenic substrate, 5-bromo-4-chloro-3-indoxyl phosphate-p-toluidine (X-Pi). This result indicates that in E. coli, X-Pi is transported exclusively by the Phn system, whereas DIPP (or its metabolite) may be transported by both Phn and Glp systems.
Methods in gene biotechnology (1997)

Approaches to Novel Research Rapid Isolation of Specific cDNAs or Genes by PCR Construction and Screening of Subtracted and Complete Expression cDNA Libraries Subcloning of Genes or DNA Fragments Nonisotopic and Isotopic DNA or RNA Sequencing Information Superhighway and Computer Databases of Nucleic Acids and Proteins Characterization of DNA or Genes by Southern Blot Hybridization Gene Overexpression by Sense RNA in Mammalian Systems Gene Underexpression in Cultured Cells and Animals by Antisense DNA and RNA Strategies Analysis of Gene Expression at the RNA Level Analysis of Gene Expression at the Protein Level Analysis of Cellular DNA or Abundance mRNA by Radioactive In Situ Hybridization (RISH) Localization of DNA or Abundance of mRNA by Fluorescence In Situ Hybridization (FISH) In Situ PCR Hybridization of Low Copy Genes and In Situ RT-PCR Detection of Low Abundance mRNAs Isolation and Characterization of Genes from Genomic DNA Libraries Culture of Mouse Embry onic Stem Cells as a Model Mammalian Cell Line for Gene Expression New Strategies for Gene Knockout Large Scale Expression and Purification of Recombinant Proteins in Cultured Cells Index All chapters contain Troubleshooting Guides and References
Widespread occurrence of a highly conserved RING‐H2 zinc finger motif in the model plant Arabidopsis thaliana (1998)

Several novel Arabidopsis thaliana proteins containing a RING-H2 zinc finger motif were predicted after database searches. Alignment of 29 RING-H2 finger sequences shows that the motif is strikingly conserved in otherwise unrelated proteins. Only short, non-conserved polar/charged sequences distinguish these domains. The RING-H2 domain is most often present in multi-domain structures, a number of which are likely to contain a membrane-spanning region or an additional zinc finger. However, there are several small (126-200 residues) proteins consisting of an N-terminal domain, rich in aliphatic residues, and a C-terminal RING-H2 domain. Reverse-transcription PCR suggests that the RING-H2 genes are widely expressed at low levels.
Hemoglobin Nigeria (alpha-81 Ser replaced by Cys):a new variant associated with alpha-thalassemia (1980)

Hematologic evaluation of a Nigerian obstetrical patient disclosed the presence of sickle-cell trait as well as evidence of a hemoglobin alpha-chain abnormality. Hemoglobins containing the variant alpha-chain were isolated by DEAE-cellulose column chromatography, and analysis of the purified alpha-chain demonstrated a ser replaced by cys substitution at alpha-81. The abnormal alpha-chain represented approximately 45% of the total, and hemoglobins containing this alpha-chain appeared to have normal stability and functional properties. In addition to the abnormal hemoglobins that were identified in this patient, she also was found to have persistent microcytosis in the absence of iron deficiency, and the percentage of HbS in her erythrocytes was less than that usually present in individuals with sickle cell trait. These findings, together with a reduced alpha/beta globin synthesis ratio from her peripheral blood reticulocytes, indicated that the presence of alpha-thalassemia trait. Hematologic findings from members of the patients's family suggest that an alpha-thalassemia gene may be linked to that of the structurally abnormal alpha-chain.
Signal Duration and Signal Frequency in Relation to Auditory Sensitivity (1969)

Levels of monaural signals at behavioral threshold were determined by a psychophysical method of adjustment for seven highly trained listeners. Thresholds were studied as a function of signal frequency (octave steps, from 0.125 to 8 kHz) and of signal duration (logarithmic steps, from 16 to 1024 msec). Measurements were made in the presence of a contralateral broad-band masking noise with a spectrum level of 30 dB SPL. The time constant, τ estimated from at least 12 replications of each measurement, was found to range systematically from values considered normal (125–175 msec) by some earlier investigators, at low frequencies, to much lower values (30–70 msec) at high frequencies. Comparison between the performance of listeners with normal audiograms and those with high-frequency hearing loss shows this interaction between frequency and the time constant to be similar for both samples. The data are also compared to the results of a second experiment that employed a two-alternative forced-choice psychophysical method.
Web server technology : the advanced guide for World Wide Web information providers (1996)

Chapter 1 Introduction Chapter 2 Web Server Technology Chapter 3 Web Scripts, Gateways, and Forms Chapter 4 Architecture, Configuration, and Performance of Web Servers Chapter 5 Web Document Distribution and Caching Chapter 6 Searching for Information on the Web Chapter 7 Secure Web Services Chapter 8 Digital Commerce: Risks, Requirements, and Technologies
Potential role of apolipoprotein-E in fibrillogenesis. (1994)

Immunohistochemical and biochemical studies have demonstrated several different proteins in amyloid deposits that are not intrinsic components of the fibril itself but may play a role in their deposition and fibril formation. We compared the distribution of several amyloid-associated proteins, ie, amyloid P component, apolipoprotein-E, apolipoprotein-J, and vitronectin, in the deposits of several different amyloids, in particular light chain amyloid, with those in the deposits of nonamyloid monoclonal immunoglobulin, which may be considered a form of preamyloid disease. Although 100% of amyloid specimens (7 amyloid A, 15 immunoglobulin light chain, and 1 transthyretin) had amyloid P component and 100% had apolipoprotein-E (2 amyloid A, 10 immunoglobulin light chain, and 1 transthyretin) co-localized with the primary amyloid protein, none of the monoclonal nonamyloid cases (14 light chain deposition disease and 6 light and heavy chain deposition disease) had amyloid P component and only 1 of 11 had apolipoprotein-E. On the other hand, staining for apolipoprotein-J and vitronectin was positive in 100% of cases of amyloid and nonamyloid monoclonal deposits. The association between the presence of apolipoprotein-E and amyloid P component in the fibrillar form of monoclonal light chain deposits and their absence in the nonfibrillar form of deposits suggest a role for these proteins in the process of fibrillogenesis. This lends support for the previously proposed concept that apolipoprotein-E functions as a pathological chaperone by altering the conformation of amyloidogenic proteins.
The Role of Selective Heating in the Microwave Activation of Heterogeneous Catmnsis Reactions Using a Continuous Microwave Reactor (1998)

This paper deals with the contribution of microwave heating to organic synthesis, especially to estenfication. When the reaction is conducted in a heterogeneous medium and under microwave heating, the reaction rate increases compared to classical heating under the same conditions. This is due to selective heating of the catalyst particles creating hot spots, resulting in an increased reaction rate. The temperature of the reactive site was calculated to be 9–18 K above the bulk temperature. A new continuous flow microwave reactor has been tested in order to show the role of selective heating of the catalyst in the activation of organic reactions under microwave heating.
Muscle LIM protein: expressed in slow muscle and induced in fast muscle by enhanced contractile activity (1999)

To identify early changes in gene expression during the fast-to-slow transition induced by chronic low-frequency stimulation, total RNA was extracted from 12-h-stimulated tibialis anterior (TA) muscles of rats and amplified by differential display RT-PCR. Among the signals of differentially expressed mRNAs, a cDNA approximately 300 bp in length, which was almost undetectable in control TA muscles but prominent in stimulated TA and normal soleus muscles, was identified. This cDNA was cloned and identified as corresponding to the mRNA of the muscle LIM protein (MLP). Its differential expression in control, stimulated TA, and soleus muscles was verified by Northern blotting. Antibodies against MLP were used to identify by immunoblot analysis a protein of 22 kDa, the predicted molecular mass of MLP. Immunohistochemistry revealed strong reactivity for MLP in all fibers of normal soleus muscle and faint staining of some type IIA and type I fibers in control TA muscle. These fibers increased in number and staining intensity in 4-day-stimulated TA muscle. MLP thus seems to play an essential role during the rearrangement of cytoskeletal and/or myofibrillar structures in transforming adult muscle fibers.
TLR3 Deletion Limits Mortality and Disease Severity due to Phlebovirus Infection (2006)

TLR3 was the first member of the TLR family of pattern recognition receptors found to detect a conserved viral molecular pattern, dsRNA, yet supporting evidence for a major role in host defense against viral pathogens is limited. Punta Toro virus (PTV) has been shown to produce severe infection in mice, modeling disease caused by the related highly pathogenic Rift Valley fever phlebovirus in humans and domesticated ungulates. Using TLR3-deficient mice, we investigated the involvement of TLR3 in host defense against PTV infection. Compared with wild-type, TLR3(-/-) mice demonstrate increased resistance to lethal infection and have reduced liver disease associated with hepatotropic PTV infection. Infectious challenge produced comparable peak liver and serum viral loads; however, TLR3(-/-) mice were able to clear systemic virus at a slightly faster rate. Cytokine profiling suggests that TLR3 plays an important role in PTV pathogenesis through the overproduction of inflammatory mediators, which may be central to the observed differences in survival and disease severity. Compared with TLR3-deficient mice, IL-6, MCP-1, IFN-gamma, and RANTES were all present at higher levels in wild-type animals. Most dramatic was the exaggerated levels of IL-6 found systemically and in liver tissue of infected wild-type mice; however, IL-6-deficient animals were found to be more susceptible to lethal PTV infection. Taken together, we conclude that the TLR3-mediated response to PTV infection is detrimental to disease outcome and propose that IL-6, although critical to establishing antiviral defense, contributes to pathogenesis when released in excess, necessitating its controlled production as is seen with TLR3(-/-) mice.
Extension of Life-Span by Loss of CHICO, a Drosophila Insulin Receptor Substrate Protein (2001)

The Drosophila melanogaster gene chico encodes an insulin receptor substrate that functions in an insulin/insulin-like growth factor (IGF) signaling pathway. In the nematode Caenorhabditis elegans, insulin/IGF signaling regulates adult longevity. We found that mutation of chico extends fruit fly median life-span by up to 48% in homozygotes and 36% in heterozygotes. Extension of life-span was not a result of impaired oogenesis in chico females, nor was it consistently correlated with increased stress resistance. The dwarf phenotype of chico homozygotes was also unnecessary for extension of life-span. The role of insulin/IGF signaling in regulating animal aging is therefore evolutionarily conserved.
Controlling the surface enhanced Raman effect via the nanoshell geometry (2003)

Systematic variation of the internal geometry of a dielectric core-metal shell nanoparticle allows the local electromagnetic field at the nanoparticle surface to be precisely controlled. The strength of the field as a function of core and shell dimension is measured by monitoring the surface enhanced Raman scattering (SERS) response of nonresonant molecular adsorbates (para-mercaptoaniline) bound to the nanoparticle surface. The SERS enhancement appears to be directly and exclusively due to nanoparticle geometry. Effective SERS enhancements of 106 are observable in aqueous solution, which correspond to absolute enhancements of 1012 when reabsorption of Raman emission by nearby nanoparticles is taken into account.
Interactions of CD80 and CD86 with CD28 and CTLA4 (1996)

CD80 and CD86 are cell surface glycoproteins expressed on a variety of professional APCs. They have attracted much attention due to their function as potent costimulators of T lymphocyte function through their interaction with CD28 and possibly CTLA4. Because inhibitors of this interaction may have therapeutic relevance in human autoimmune disease, we investigated the properties of linear peptides derived from conserved regions of CTLA4 and CD80 known to be essential for binding. None of these peptides were sufficient to bind ligand, nor did they act as potent competitive inhibitors. Conformationally constrained versions of the CTLA4 motif were also inactive. These results suggested that other parts of the proteins are important in determining binding, so a series of modified CD80 and CD86 molecules were constructed in an attempt to identify other binding determinants. Insertion of two residues between the two Ig domains of CD80 resulted in decreased affinity for CTLA4, but a similar mutation in CD86 was without effect. We also identified another asymmetry between CD80 and CD86 in that the V domain of CD86 but not that of CD80 is sufficient for CTLA4 binding. The CD86-V domain appears to have CTLA4 binding properties equivalent to that of intact CD86. These data illustrate a fundamental difference between these costimulatory molecules and suggest a mechanism by which they may be differentially recognized by receptors on the T cell surface.
A Speech Coder Post-Processor Controlled By Side-Information (2006)

Speech coders provide high speech quality at low rates. However they perform poorly when encoding non-speech signals. This paper proposes a new enhancement algorithm requiring minimum side information to reduce the effect of this shortcoming. The enhancement algorithm consists of post-processing the speech decoder output in the spectral domain. Specifically, some frequency components are reduced or forced to zero when the corresponding frequency content is poorly described by the speech coder. The choice of modifying spectral components is determined at the encoder, thus requiring us to transmit the decision information. Experiments combining the AMR-WB speech codec and the proposed audio enhancement show that the quality for music signals is improved significantly while not affecting the quality for speech inputs.
A New Molecular Target of Insulin Action: Regulating the Pivotal PDK1 (2001)

Over the last several years, a great level of interest has rallied behind understanding how the pivotal kinase, 3'-phosphoinositide dependent kinase 1 (PDK1) is regulated. PDK1 phosphorylates and activates members of the AGC kinase family shown to be activated downstream of phosphoinositide 3-kinase (P13K); however, the functional dependency of PDK1 on P13K for activation of its targets is less clear. The P13K signaling pathway mediates numerous cellular responses upon growth factor and hormone stimulation. Specifically, P13K signaling influences many of the metabolic and mitogenic functions of the anabolic hormone, insulin. Thus, the regulation of P13K and its downstream targets by insulin has become an important topic for investigation. Given its central role as the kinase upstream of those signaling pathways linked to P13K, the regulation of PDK1 by insulin and other factors is at the height of many of these investigations. Current theories on PDK1 regulation propose substrate conformation and subcellular localization as the primary mediators of PDK1 function. The array of PDK1 substrates suggests, however, that in cells PDK1 may be more tightly regulated. Recent data support phosphorylation as a potential regulatory mechanism that may play an additional role in directing the specificity of PDK1 towards its physiological substrates. The combination of these regulatory mechanisms along with the potential for multiple PDK1 isoforms with select tissue distribution may contribute to the diversified actions of insulin signaling. The targeting of these various aspects of PDK1 regulation may provide for novel therapeutic treatments for diseases such as diabetes and cancer.
Cancer associated fibroblasts: the dark side of the coin. (2011)

Valid experimental evidence has recently shown that progression of malignant tumors does not depend exclusively on cell-autonomous properties of the cancer cells, but is also deeply influenced by tumor stroma reactivity and undergoes a strict microenvironmental control. Beside structural environmental components as extracellular matrix (ECM) or hypoxia, stromal cells as macrophages, endothelial cells, and cancer-associated fibroblasts (CAFs) play a definite role in cancer progression. This review summarizes our current knowledge on the role of CAFs in tumor progression towards an aggressive phenotype, with particular emphasis on invasiveness, stemness, and preparation of metastatic niche. The controversial origins of CAFs as well as the therapeutical implications of targeting CAFs for anticancer therapy are discussed.
The method of axial drift compensation of laser differential confocal microscopy based on zero-tracking (2015)

Laser differential confocal microscopy (DCM) has advantages of high axial resolution and strong ability of focus identification. However, the imaging mechanism of point scanning needs long measurement time, in the process due to itself mechanical instability and the influence of environment vibration the axial drift of object position is inevitable, which will reduce lateral resolution of the DCM. To ensure the lateral resolution we propose an axial drift compensation method based on zero-tracking in this paper. The method takes advantage of the linear region of differential confocal axial response curve, gets axial drift by detecting the laser intensity; uses grating sensor to monitor the real-time axial drift of lifting stage and realizes closed-loop control; uses capacitive sensor of objective driver to measure its position. After getting the axial drift of object, the lifting stage and objective driver will be driven to compensate position according to the axial drift. This method is realized by using Visual Studio 2010, and the experiment demonstrates that the compensation precision of the proposed method can reach 6 nm. It is not only easy to implement, but also can compensate the axial drift actively and real-timely. Above all, this method improves the system stability of DCM effectively.