gebhart/patrepeval huggingface dataset:
Time‐Resolved Fluorescence Measurements (2000)

This unit provides a detailed review and technical discussion of the principles of time-resolved fluorescence. The unique feature of this particular unit is that the principles are directly tied to the use of flow cytometry. There are a number of advantages in being able to discriminate between fluorochromes based upon their lifetimes as opposed to their emission wavelengths. One particularly good application is the determination of bound versus free molecules. The author covers both the theoretical and practical components of measuring fluorescence in the time domain. In addition, the unit provides a listing of the most common fluorescent dyes with comparative data of lifetime and excitation conditions.
Molecular crowding enhances native state stability and refolding rates of globular proteins (2005)

The presence of macromolecules in cells geometrically restricts the available space for poplypeptide chains. To study the effects of macromolecular crowding on folding thermodynamics and kinetics, we used an off-lattice model of the all-beta-sheet WW domain in the presence of large spherical particles whose interaction with the polypeptide chain is purely repulsive. At all volume fractions, phi(c), of the crowding agents the stability of the native state is enhanced. Remarkably, the refolding rates, which are larger than the value at phi(c) = 0, increase nonmonotonically as phi(c) increases, reaching a maximum at phi(c)=phi(c)(*). At high values of phi(c), the depletion-induced intramolecular attraction produces compact structures with considerable structure in the denatured state. Changes in native state stability and folding kinetics at phi(c) can be quantitatively mapped onto confinement in a volume-fraction-dependent spherical pore with radius R(s) approximately (4pi/3phi(c))(1/3) R(c) (R(c) is the radius of the crowding particles) as long as phi(c)< or =phi(c)(*). We show that the extent of native state stabilization at finite phi(c) is comparable with that in a spherical pore. In both situations, rate enhancement is due to destabilization of the denatured states with respect to phi(c) = 0.
Wavelength multiplexer based on SiO/sub 2/-Ta/sub 2/O/sub 5/ arrayed-waveguide grating (1994)

The characteristics of a wavelength multiplexer based on an arrayed-waveguide grating are carefully investigated by using the grating theory and related experiments. A 28-channel multiplexer is designed and fabricated as SiO/sub 2/-Ta/sub 2/O/sub 5/ waveguides on a 1 cm/spl times/2 cm substrate. The designed wavelength channel spacing of 1 nm is obtained. The crosstalk to an adjacent channel is -15 dB. The measured minimum loss is 4.2 dB, which is composed of 3.4 dB excess loss and 0.8 dB grating loss.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mechanisms of Protection against Damage Mediated by the Maillard Reaction in Aging (1991)

In order to prevent or escape the ongoing damage to proteins and DNA resulting from amino-carbonyl reactions, the organism has to have powerful defense mechanisms. If the Maillard reaction played a role in determining longevity among mammalian species, one would expect protective mechanisms to be more developed in long- versus short-lived species. This article summarizes current knowledge in this field, and discusses the concept of anti-Maillard mechanisms as a basis for the genetic regulation of molecular damage by reducing sugars in aging and diabetes.
Synthetic and mechanistic studies on esperamicin A1 and calichemicin .gamma.1. Molecular strain rather than .pi.-bond proximity determines the cycloaromatization rates of bicyclo[7.3.1]enediynes (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic and mechanistic studies on esperamicin A1 and calichemicin .gamma.1. Molecular strain rather than .pi.-bond proximity determines the cycloaromatization rates of bicyclo[7.3.1]enediynesPhilip Magnus, Simon Fortt, Thomas Pitterna, and James P. SnyderCite this: J. Am. Chem. Soc. 1990, 112, 12, 4986–4987Publication Date (Print):June 1, 1990Publication History Published online1 May 2002Published inissue 1 June 1990https://pubs.acs.org/doi/10.1021/ja00168a068https://doi.org/10.1021/ja00168a068research-articleACS PublicationsRequest reuse permissionsArticle Views370Altmetric-Citations87LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Discovery of IL-6 and Development of Anti-IL-6R Antibody (2019)

A series of our studies on IL-6 have revealed that it has a pleiotropic activity in various tissues and cells and its deregulated expression is responsible for several chronic inflammations and hemopoietic malignancies.Humanized antibody against 80kd IL-6R (Tocilizumab) has shown significant therapeutic effect in RA, JIA, Castleman's diseases and several other autoimmune inflammatory diseases, such as, giant cell arteritis, reactive arthritis, polymyalgia rheumatica and adult still's disease. Cytokine storm induced by CAR-T cell therapy has been shown to be controlled by Tocilizumab.Therapeutic effect of Tocilizumab confirmed that over and constitutive-production of IL-6 is responsible for the pathogenesis of autoimmune diseases.Then, the question to be asked is how is IL-6 production regulated. We identified a novel molecule called Arid5a which binds with the 3'-UTR of IL-6 mRNA and protects its degradation by competing with Regnase-1. Interestingly, this molecule is present in nuclei and inflammatory stimulation induced translocation of Arid5a from nuclei into cytoplasm and it competes with Regnase-1 for the protection of mRNA of IL-6.Our study indicates that Arid5a is one of the key molecules for inflammation as well as the development of septic shock.The results also suggest the therapeutic potential of anti-agonistic agents for Arid5a in the prevention of various inflammatory diseases and septic shock.
Dual-color imaging of nascent angiogenesis and its inhibition in liver metastases of pancreatic cancer. (2006)

As previously shown, the stem cell marker nestin is expressed in nascent blood vessels in transgenic nestin-driven green fluorescent protein (ND-GFP) nude mice. This mouse model was recently utilized to evaluate angiogenesis in primary tumors in an orthotopic model of pancreatic cancer. In the present study, nascent angiogenesis of pancreatic cancer liver metastasis in the ND-GFP transgenic nude mice after splenic injection of low-passage xPA-1 human pancreatic cancer cells expressing red fluorescent protein (RFP) was visualized by dual-color fluorescence imaging. ND-GFP was highly expressed in proliferating endothelial cells and nascent blood vessels in the growing liver metastasis. Immunohistochemical staining showed that CD31 co-localized in ND-GFP-expressing nascent blood vessels. The density of nascent blood vessels in the tumor was readily quantitated. Gemcitabine significantly decreased the mean nascent blood vessel density in the pancreatic liver metastases. In conclusion, the dual-color model of the ND-GFP nude mouse with RFP-expressing pancreatic cancer liver metastases, enabled the simultaneous visualization and quantitation of nascent angiogenesis and its response to angiogenesis inhibitors. This model will be useful for understanding the mechanism of angiogenesis of pancreatic cancer liver metastasis and for the discovery of effective new inhibitors of this process.
Statistical analysis of COPD exacerbations (2008)

Bronchoconstriction, after removal of a catecholamine-producing tumour, is physiologically foreseeable owing to the sudden deprivation of catecholamines, as well as deprivation of other tumour-secreted bronchodilator substances, such as adrenomedullin [4], vasoactive intestinal peptide or pituitary adenylate cyclase-activating peptide There are, however, few reports of respiratory problems in patients with pheochromocytoma and all, in contrast to ours, had a history of asthma and/or were being treated with b-blockers Our patient has, since the acute post-operative period, been feeling perfectly well. She is back in the gym on a regular basis, her cardiac frequency is normal and she has not had any further respiratory problems.
Lipocortin-1 is an endogenous inhibitor of ischemic damage in the rat brain. (1991)

Lipocortin-1 (annexin-1) is an endogenous peptide with antiinflammatory properties. We have previously demonstrated lipocortin immunoreactivity in certain glial cells and neurons in the rat brain (Strijbos, P.J.L.M., F.J.H. Tilders, F. Carey, R. Forder, and N.J. Rothwell. 1990. Brain Res. In press.), and have shown that an NH2-terminal fragment (1-188) of lipocortin-1 inhibits the central and peripheral actions of cytokines on fever and thermogenesis in the rat in vivo (Carey, F., R. Forder, M.D. Edge, A.R. Greene, M.A. Horan, P.J.L.M. Strijbos, and N.J. Rothwell. 1990. Am. J. Physiol. 259:R266; and Strijbos, P.J.L.M., J.L. Browning, M. Ward, R. Forder, F. Carey, M.A. Horan, and N.J. Rothwell. 1991. Br. J. Pharmacol. In press.). We now report that intracerebroventricular administration of lipocortin-1 fragment causes marked inhibition of infarct size (60%) and cerebral edema (46%) measured 2 h after cerebral ischemia (middle cerebral artery occlusion) in the rat in vivo. The lipocortin-1 fragment was effective when administered 10 min after induction of ischemia. Ischemia caused increased expression of lipocortin-1 around the area of infarction as demonstrated by immunocytochemistry. Intracerebroventricular injection of neutralizing antilipocortin-1 fragment antiserum increased the size of infarct (53%) and the development of edema (29%). These findings indicate that lipocortin-1 is an endogenous inhibitor of cerebral ischemia with considerable therapeutic potential.
Properties of porous anodic aluminum oxide films as membranes. (1984)

The details of a method of preparing anodic aluminum oxide membranes are presented. The porous oxide layer consists of close-packed cells of oxide, hexagonal in shape, each of which contains a single pore formed perpendicularly to the surface of the aluminum substrate. This special structural feature is essentially important for ultrafiltration and gas separation. The rejection characteristics are examined, using aqueous and nonaqueous solutions of macromolecules. The permeability of gases is also examined at different temperatures. The flow of gases is explained by the Knudsen regime alone.
Helium Detection via Field Ionization from Carbon Nanotubes (2003)

A novel, high-efficiency detector for neutral atoms such as helium is described. The design uses multiwalled carbon nanotubes (MWNTs), grown by chemical vapor deposition on a steel support wire. Application of a positive bias to the MWNTs generates electric fields sufficient to field-ionize passing gas-phase atoms. Under ultrahigh vacuum conditions, the detector was demonstrated to be capable of ionising and detecting even helium gas, the element with the highest ionization potential.
Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. (2003)

Histone acetylation has a central role in the control of gene expression, influencing transcriptional control of many genes, including tumor suppressor genes. PXD101 is a novel hydroxamate-type inhibitor of histone deacetylase activity that inhibits histone deacetylase activity in HeLa cell extracts with an IC(50) of 27 nM and induces a concentration-dependent (0.2-5 micro M) increase in acetylation of histone H4 in tumor cell lines. PXD101 is cytotoxic in vitro in a number of tumor cell lines with IC(50)s in the range 0.2-3.4 micro M as determined by a clonogenic assay and induces apoptosis. Treatment of nude mice bearing human ovarian and colon tumor xenografts with PXD101 (10-40 mg/kg/day i.p.) daily for 7 days causes a significant dose-dependent growth delay with no obvious signs of toxicity to the mice. Growth delay is also observed for xenografts of cisplatin-resistant ovarian tumor cells. A marked increase in acetylation of H4 is detected in blood and tumor of mice 3 h after treatment with PXD101. The inhibition of growth of human tumor xenografts in mice, with no apparent toxicity, suggests that PXD101 has potential as a novel antitumor agent. Furthermore, the ability to measure histone acetylation in blood samples could provide a suitable pharmacodynamic end point to monitor drug activity.
Disassembly of executable code revisited (2003)

Machine code disassembly routines form a fundamental component of software systems that statically analyze or modify executable programs, e.g., reverse engineering systems, static binary translators, and link-time optimizers. The task of disassembly is complicated by indirect jumps and the presence of non-executable data - jump tables, alignment bytes, etc. - in the instruction stream. Existing disassembly algorithms are not always able to cope successfully with executable files containing such features, and they fail silently - i.e., produce incorrect disassemblies without any indication that the results they are producing are incorrect. In this paper we examine two commonly-used disassembly algorithms and illustrate their shortcomings. We propose a hybrid approach that performs better than these algorithms in the sense that it is able to detect situations where the disassembly may be incorrect and limit the extent of such disassembly errors. Experimental results indicate that the algorithm is quite effective: the amount of code flagged as incurring disassembly errors is usually quite small.
Fade: a vehicle detection and tracking system featuring monocular color vision and radar data fusion (2003)

This paper presents Fade, a vehicle detection and tracking system featuring monocular color vision and radar data fusion. Its main originality resides in its low-level fusion system. At each step and for each target, the fusion system fuses the results of four different image processing algorithms and radar information by automatically combining 12 different features and generating many possible target position proposals. It generates a belief network organized in three layers: sources, position proposals, and correlation between proposals. An inference algorithm is then used to find out the actual position of the target, by deducing which observations are wrong. The overall system runs in real time and has been evaluated on a variety of scenarios recorded in a real car using /sup RT/Maps. Fade yields very good detection results in most cases.
Drug Delivery Across the Blood-Brain Barrier (2004)

The brain is protected and isolated from the general circulation by a highly efficient blood-brain barrier. This is characterised by relatively impermeable endothelial cells with tight junctions, enzymatic activity and active efflux transport systems. Consequently the blood-brain barrier is designed to permit selective transport of molecules that are essential for brain function. This creates a considerable challenge for the treatment of central nervous system diseases requiring therapeutic levels of drug to enter the brain. Some small lipophilic drugs diffuse across the blood-brain barrier- sufficiently well to be efficacious. However, many potentially useful drugs are excluded. This review provides an insight into the current research into technologies to target small molecules, peptides and proteins to the brain. A brief review of the nature of the blood-brain barrier and its transport mechanisms is provided. Strategies to target and improve transport across the blood-brain barrier include the prodrug-lipidisation approach, sequential metabolism chemical delivery systems, drug-vectors, liposomes and nanoparticles. Included is the discussion of techniques to minimise clearance from the circulation by the reticuloendothelial system in order to extend circulation residence time and optimise the opportunity for interaction between the drug delivery system and the blood-brain barrier.
Bacillus sporulation gene spo0H codes for sigma 30 (sigma H) (1988)

The DNA sequences of the spo0H genes from Bacillus licheniformis and B. subtilis are described, and the predicted open reading frames code for proteins of 26,097 and 25,447 daltons, respectively. The two spo0H gene products are 91% identical to one another and about 25% identical to most of the procaryotic sigma factors. The predicted proteins have a conserved 14-amino-acid sequence at their amino terminal end, typical of sigma factors. Antibodies raised against the spo0H gene product of B. licheniformis specifically react with RNA polymerase sigma factor protein, sigma 30, purified from B. subtilis. We conclude that the spo0H genes of B. licheniformis and B. subtilis code for sigma 30, now known as sigma H.
Complement and cytokine response in acute Thrombotic Thrombocytopenic Purpura (2013)

Complement dysregulation is key in the pathogenesis of atypical Haemolytic Uraemic Syndrome (aHUS), but no clear role for complement has been identified in Thrombotic Thrombocytopenic Purpura (TTP). We aimed to assess complement activation and cytokine response in acute antibody-mediated TTP. Complement C3a and C5a and cytokines (interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor, interferon-γ and IL-17a) were measured in 20 acute TTP patients and 49 remission cases. Anti-ADAMTS13 immunoglobulin G (IgG) subtypes were measured in acute patients in order to study the association with complement activation. In acute TTP, median C3a and C5a were significantly elevated compared to remission, C3a 63·9 ng/ml vs. 38·2 ng/ml (P < 0·001) and C5a 16·4 ng/ml vs. 9·29 ng/ml (P < 0·001), respectively. Median IL-6 and IL-10 levels were significantly higher in the acute vs. remission groups, IL-6: 8 pg/ml vs. 2 pg/ml (P = 0·003), IL-10: 6 pg/ml vs. 2 pg/ml (P < 0·001). C3a levels correlated with both anti-ADAMTS13 IgG (rs = 0·604, P = 0·017) and IL-10 (rs = 0·692, P = 0·006). No anti-ADAMTS13 IgG subtype was associated with higher complement activation, but patients with the highest C3a levels had 3 or 4 IgG subtypes present. These results suggest complement anaphylatoxin levels are higher in acute TTP cases than in remission, and the complement response seen acutely may relate to anti-ADAMTS13 IgG antibody and IL-10 levels.
Analysis of monoterpenoids in glandular trichomes of the catmint Nepeta racemosa (1997)

Plants within the Lamiaceae are characterized by their production of essential oils, largely composed of monoterpenoids. They also possess on their aerial surfaces different types of trichomes, including relatively large peltate glandular trichomes. Observation of leaves of the catmint Nepeta racemosa , using cryogenic scanning electron microscopy, showed that around 3000 peltate trichomes are present on a single expanded leaf. An approach has been developed for sampling directly from the subcuticular cavity of such trichomes, in order to characterize qualitatively and quantitatively their contents. Gland samples from Nepeta spp. were analysed by combined gas chromatography‐mass spectrometry. These analyses have confirmed that the monoterpenoids characteristic of these species (nepetalactones) accumulate within the subcuticular cavity of peltate glandular trichomes. Qualitative analysis showed that three different nepetalactone stereoisomers were accumulated in different proportions in peltate glands from individual N. racemosa plants. Quantitative analysis showed that individual peltate glands accumulate around 30 ng of nepetalactone by maturity, and that accumulation of nepetalactone probably occurs exclusively within this gland type.
Intrinsic Resistance to MEK Inhibition in KRAS Mutant Lung and Colon Cancer through Transcriptional Induction of ERBB3 (2014)

There are no effective therapies for the ~30% of human malignancies with mutant RAS oncogenes. Using a kinome-centered synthetic lethality screen, we find that suppression of the ERBB3 receptor tyrosine kinase sensitizes KRAS mutant lung and colon cancer cells to MEK inhibitors. We show that MEK inhibition results in MYC-dependent transcriptional upregulation of ERBB3, which is responsible for intrinsic drug resistance. Drugs targeting both EGFR and ERBB2, each capable of forming heterodimers with ERBB3, can reverse unresponsiveness to MEK inhibition by decreasing inhibitory phosphorylation of the proapoptotic proteins BAD and BIM. Moreover, ERBB3 protein level is a biomarker of response to combinatorial treatment. These data suggest a combination strategy for treating KRAS mutant colon and lung cancers and a way to identify the tumors that are most likely to benefit from such combinatorial treatment.
Effect of copy number and mRNA processing and stabilization on transcript and protein levels from an engineered dual‐gene operon (2002)

To study the effect of mRNA stability and DNA copy number on protein production from a dual-gene operon, a synthetic operon containing the reporter genes gfp and lacZ under the control of the araBAD promoter was placed in pMB1-based (approximately 100 copies/cell) and F plasmid-based (approximately 1 copy/cell) vectors. DNA cassettes encoding secondary structures were placed at the 5' and 3' ends of the genes and a putative RNase E site was placed between the two genes. Although the copy number of the pMB1-based vectors was approximately 100-fold greater than the copy number of the F plasmid-based vectors, transcript and protein levels from the pMB1-based vector were not 100-fold greater than from the F plasmid-based vectors. In identical plasmid backbones, different combinations of mRNA control elements were used to alter steady-state levels of transcripts. Control elements that amplified the stability of one coding region relative to another amplified the ratio of protein produced from those transcripts. The effects of mRNA stability control elements were greater at low inducer concentrations, where mRNA levels limit protein production, than at high inducer concentrations. Although we can alter mRNA and protein levels through copy number, induction level, and mRNA stability control elements, some aspect of gene expression remains dependent on inherent characteristics of the coding region.