gebhart/patrepeval huggingface dataset:
Acridine- and cholesterol-derivatized solid supports for improved synthesis of 3'-modified oligonucleotides (1991)

New solid supports are described which allow the direct synthesis of oligonucleotides bearing either cholesterol or acridine at the 3'-terminus. A stereochemically defined amino diol was prepared by reduction of N-Cbz-hydroxy-L-proline. This linker molecule was first acylated with the desired conjugate molecule, then protected as the dimethoxytrityl ether. The remaining secondary hydroxyl group was succinylated and immobilized on a controlled-pore glass support. 3'-Modified oligodeoxynucleotides (ODNs) were prepared from these supports by using standard phosphoramidite coupling and deprotection conditions. A cholesterol-modified support was prepared from cholesterol chloroformate and the amino diol linker. Two types of acridine-modified solid supports were prepared from acridine tetrafluorophenyl esters with linker arms of different length. In an alternative synthesis of 3'-derivatized ODNs, these active esters were also utilized for acylation of a 3'-amine-modified ODN. A thermal denaturation study was done to determine the effect of the different linker arms on hybridization to a complementary ODN target. Facile synthesis and purification of the 3'-modified ODNs makes these functionalized solid supports especially useful for preparation of oligonucleotides bearing these and other modifications.
2,4-Dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), an Active Agent in the Resistance of Maize to the European Corn Borer123 (1967)

Journal Article 2,4-Dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), an Active Agent in the Resistance of Maize to the European Corn Borer Get access J. A. Klun, J. A. Klun Search for other works by this author on: Oxford Academic PubMed Google Scholar C. L. Tipton, C. L. Tipton Search for other works by this author on: Oxford Academic PubMed Google Scholar T. A. Brindley T. A. Brindley Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Economic Entomology, Volume 60, Issue 6, 1 December 1967, Pages 1529–1533, https://doi.org/10.1093/jee/60.6.1529 Published: 01 December 1967 Article history Accepted: 01 July 1967 Published: 01 December 1967
Susceptibility of Treatment-Naive Hepatitis C Virus (HCV) Clinical Isolates to HCV Protease Inhibitors (2010)

In order to assess the natural variation in susceptibility to hepatitis C virus (HCV) NS3 protease inhibitors (PIs) among untreated HCV patient samples, the susceptibilities of 39 baseline clinical isolates were determined using a transient-replication assay on a panel of HCV PIs, including two α-ketoamides (VX-950 and SCH-503034) and three macrocyclic inhibitors (MK-7009, ITMN-191, and TMC-435350). Some natural variation in susceptibility to all HCV PIs tested was observed among the baseline clinical isolates. The susceptibility to VX-950 correlated strongly with the susceptibility to SCH-503034. A moderate correlation was observed between the susceptibilities to ITMN-191 and MK-7009. In contrast, the phenotypic correlations between the α-ketoamides and macrocyclic inhibitors were significantly lower. This difference is partly attributable to reduced susceptibility of the HCV variants containing the NS3 polymorphism Q80K (existing in 47% of genotype 1a isolates) to the macrocyclic compounds but no change in the sensitivity of the same variants to the α-ketoamides tested. Our results suggest that the natural variation in baseline susceptibility may contribute to different degrees of antiviral response among patients in vivo, particularly at lower doses.
Low Rate Sampling Schemes for Time Delay Estimation (2009)

Time delay estimation arises in many applications in which a multipath medium has to be identified from pulses transmitted through the channel. Various approaches have been proposed in the literature to identify time delays introduced by multipath environments. However, these methods either operate on the analog received signal, or require high sampling rates in order to achieve reasonable time resolution. In this paper, our goal is to develop a unified approach to time delay estimation from low rate samples of the output of a multipath channel. Our methods result in perfect recovery of the multipath delays from samples of the channel output at the lowest possible rate, even in the presence of overlapping transmitted pulses. This rate depends only on the number of multipath components and the transmission rate, but not on the bandwidth of the probing signal. In addition, our development allows for a variety of different sampling methods. By properly manipulating the lowrate samples, we show that the time delays can be recovered using the well-known ESPRIT algorithm. Combining results from sampling theory with those obtained in the context of direction of arrival estimation methods, we develop necessary and sufficient conditions on the transmitted pulse and the sampling functions in order to ensure perfect recovery of the channel parameters at the minimal possible rate.
SPECTRAL PERTURBATIONS OF THE AEQUOREA GREEN‐FLUORESCENT PROTEIN (1982)

Abstract— In the jellyfish Aequorea, the green‐fluorescent protein (GFP) functions as the in vivo bio‐luminescence emitter via energy transfer from the photoprotein aequorin. Accumulated evidence has indicated that the Aequorea GFP is a relatively inflexible protein. Present evidence, however, indicates that the chromophore environment is readily accessible to a variety of external perturbants. Native Aequorea GFP has an absorbance maximum at 395 nm and a shoulder at 470 nm. In low ionic strength buffer at neutral pH and room temperature the 395/470 nm absorbance ratio is about 2.0. We show that this ratio is highly variable depending upon temperature, ionic strength, protein concentration, and pH. A maximum ratio of 6.5 (at a protein concentration of 18.6 mg/m/) and minimum of 0.42 (at a pH of 12.2) have been measured. In the latter case, the resulting absorption and excitation spectra resemble those of Renilla GFP in spectral shape (but not wavelength maximum). In all cases as the perturbant is varied the resulting spectra pass through a sharp isosbestic point, suggesting a relatively simple two‐state mechanism. These spectral perturbations are fully reversible. On the basis of these results, we suggest that the chromophore binding site is conformationally flexible. pH‐Dependent changes in the near‐UV and visible circular dichroism spectra plus spectrophotometric titration of tyrosine residues lend additional support to this hypothesis.
αvβ6 Integrin-A Marker for the Malignant Potential of Epithelial Ovarian Cancer (2002)

The mechanism(s) responsible for the progression of non-metastatic or borderline ovarian cancer to invasive Grade I/III ovarian cancer is still unknown. An epithelium-restricted integrin, alpha(v)beta(6), is present in malignant epithelia but not in normal epithelia. We studied the relative expression and distribution of alpha(v)beta(6) integrin in early and late-stage invasive (Grade I and Grade III) and non-invasive (benign and borderline) ovarian tumors of serous, mucinous, endometrioid, and clear-cell carcinoma subtypes, to assess its potential as a marker for epithelial ovarian cancer progression. Sixty-six specimens, including eight normal, 13 benign, 14 borderline, 13 Grade I, and 18 Grade III tumors were evaluated by immunohistochemistry (IHC) using a monoclonal antibody (MAb) against alpha(v)beta(6) integrin. Normal ovarian surface epithelium was negative for alpha(v)beta(6) integrin expression. All 45 carcinomas studied were positive, and the staining intensity significantly correlated with the grade of the tumor. The Grade III carcinomas of all types showed strong staining intensity. Only mucinous benign tissues were positive, and no reactivity was observed in benign serous neoplasms. On the basis of these observations, we hypothesize that the expression of alpha(v)beta(6) integrin is associated with epithelial ovarian cancer and that a gradual increase in the expression of the molecule may be a correlative index of the progression of this disease.
Intramolecular Disulfide Bonds Enhance the Antimicrobial and Lytic Activities of Protegrins at Physiological Sodium Chloride Concentrations (1996)

Protegrins are 2-kDa antimicrobial peptides that contain 16-18 amino acid residues and two intramolecular disulfide bonds. We studied the contribution of these disulfide bonds to the bactericidal activity of protegrins in physiological concentrations of NaCl by comparing protegrin PG-1 with variants that lacked one or both cysteine disulfides. Whereas the bactericidal and liposome-lytic properties of protegrin PG-1 were enhanced by adding 100 mM NaCl to the phosphate-buffered medium, NaCl addition strongly inhibited the effects of its linearized, disulfide-free variant, [A6, A8, A13, A15]protegrin-1. Whereas protegrin PG-1 manifested beta-sheet structure by CD (circular dichroism) and ATR-FTIR (attenuated-total-reflectance-Fourier-transform-infrared) spectroscopy in buffer or membrane-mimetic environments, [A6, A8, A13, A15]protegrin-1 manifested disordered structure in phosphate buffer and alpha-helical characteristics in membrane-mimetic environments. Both single-disulfide protegrin variants, [A8, A13]protegrin-1 and [A6, A15]protegrin-1, assumed beta-sheet conformations with liposomes that simulated bacterial membranes, and both retained substantial bactericidal activity when 100 mM NaCl was present. These findings demonstrate that the intramolecular disulfide bonds of protegrins are required for their antiparallel beta-sheet conformation in membrane-mimetic environments and for their potent antimicrobial activity in media containing NaCl concentrations comparable to those found in serum and extracellular fluids.
All-trans retinol, vitamin D and other hydrophobic compounds bind in the axial pore of the five-stranded coiled-coil domain of cartilage oligomeric matrix protein (1998)

The potential storage and delivery function of cartilage oligomeric matrix protein (COMP) for cell signaling molecules was explored by binding hydrophobic compounds to the recombinant five-stranded coiled-coil domain of COMP. Complex formation with benzene, cyclohexane, vitamin D3 and elaidic acid was demonstrated through increases in denaturation temperatures of 2-10 degreesC. For all-trans retinol and all-trans retinoic acid, an equilibrium dissociation constant KD = 0.6 microM was evaluated by fluorescence titration. Binding of benzene and all-trans retinol into the hydrophobic axial pore of the COMP coiled-coil domain was proven by the X-ray crystal structures of the corresponding complexes at 0.25 and 0.27 nm resolution, respectively. Benzene binds with its plane perpendicular to the pore axis. The binding site is between the two internal rings formed by Leu37 and Thr40 pointing into the pore of the COMP coiled-coil domain. The retinol beta-ionone ring is positioned in a hydrophobic environment near Thr40, and the 1.1 nm long isoprene tail follows a completely hydrophobic region of the pore. Its terminal hydroxyl group complexes with a ring of the five side chains of Gln54. A mutant in which Gln54 is replaced by Ile binds all-trans retinol with affinity similar to the wild-type, demonstrating that hydrophobic interactions are predominant.
Cytometry in cell necrobiology: Analysis of apoptosis and accidental cell death (necrosis) (1997)

The term cell necrobiology is introduced to comprise the life processes associated with morphological, biochemical, and molecular changes which predispose, precede, and accompany cell death, as well as the consequences and tissue response to cell death. Two alternative modes of cell death can be distinguished, apoptosis and accidental cell death, generally defined as necrosis. The wide interest in necrobiology in many disciplines stems from the realization that apoptosis, whether it occurs physiologically or as a manifestation of a pathological state, is an active mode of cell death and a subject of complex regulatory processes. A possibility exists, therefore, to interact with the regulatory machinery and thereby modulate the cell's propensity to die in response to intrinsic or exogenous signals. Flow cytometry appears to be the methodology of choice to study various aspects of necrobiology. It offers all the advantages of rapid, multiparameter analysis of large populations of individual cells to investigate the biological processes associated with cell death. Numerous methods have been developed to identify apoptotic and necrotic cells and are widely used in various disciplines, in particular in oncology and immunology. The methods based on changes in cell morphology, plasma membrane structure and transport function, function of cell organelles, DNA stability to denaturation, and endonucleolytic DNA degradation are reviewed and their applicability in the research laboratory and in the clinical setting is discussed. Improper use of flow cytometry in analysis of cell death and in data interpretation also is discussed. The most severe errors are due to i) misclassification of nuclear fragments and individual apoptotic bodies as single apoptotic cells, ii) assumption that the apoptotic index represents the rate of cell death, and iii) failure to confirm by microscopy that the cells classified by flow cytometry as apoptotic or necrotic do indeed show morphology consistent with this classification. It is expected that flow cytometry will be the dominant methodology for necrobiology.
SqueezeDet: Unified, Small, Low Power Fully Convolutional Neural Networks for Real-Time Object Detection for Autonomous Driving (2016)

Object detection is a crucial task for autonomous driving. In addition to requiring high accuracy to ensure safety, object detection for autonomous driving also requires real-time inference speed to guarantee prompt vehicle control, as well as small model size and energy efficiency to enable embedded system deployment. In this work, we propose SqueezeDet, a fully convolutional neural network for object detection that aims to simultaneously satisfy all of the above constraints. In our network, we use convolutional layers not only to extract feature maps but also as the output layer to compute bounding boxes and class probabilities. The detection pipeline of our model only contains a single forward pass of a neural network, thus it is extremely fast. Our model is fully-convolutional, which leads to a small model size and better energy efficiency. While achieving the same accuracy as previous baselines, our model is 30.4x smaller, 19.7x faster, and consumes 35.2x lower energy. The code is open-sourced at \url{https://github.com/BichenWuUCB/squeezeDet}.
Determination of the Structural Features of Distinct Amines Important for the Absorption of CO2 and Regeneration in Aqueous Solution (2003)

A study of carbon dioxide (CO2) absorption/desorption has been carried out to estimate the influence of the structural features of distinct amines on their CO2 absorption and regeneration. The absorption has been made at two different CO2 flow rates with a series of aqueous 5 wt % ammonia, monoethanolamine (MEA), triethanolamine (TEA), triethylamine, pyridine, pyrrolidine, 2-(2-aminoethylamino)ethanol (AEE), and N-(2-aminoethyl)-1,3-propanediamine (AEPDNH2) solutions, while the CO2 desorption has been performed by heating these solutions. The presence of two or three amino groups in AEE and AEPDNH2, the structure of tertiary amine and alkanolamine, and a nonaromatic ring of pyrrolidine might favor the CO2 absorption, while the structural features of ammonia and pyridine seem to be unfavorable. The tertiary alkanolamine is the most easy to regenerate and looses less of its CO2 loading after regeneration. It appears that AEE and AEPDNH2 would represent interesting compounds which could be used as CO2 absorbents in industrial technologies to prevent CO2 release into the atmosphere.
Long-term results of hysteroscopic myomectomy for abnormal uterine bleeding (1999)

Transcervical resection of submucous myomas is a safe and effective treatment for patients with a normal sized uterus and not more than two myomas. It is an acceptable alternative for selected other patients. The need for a combined endometrial ablation is questionable. Transcervical resection of submucous myomas will give patients a high chance of averting further surgery and should modify the way patients are counseled.
Branched Coordination Multilayers on Gold (2005)

A C3-symmetric tridentate hexahydroxamate ligand molecule was specially synthesized and used for coordination self-assembly of branched multilayers on Au surfaces precoated with a self-assembled monolayer (SAM) of ligand anchors. Layer-by-layer (LbL) growth of multilayers via metal-organic coordination using Zr4+ ions proceeds with high regularity, adding one molecular layer in each step, as shown by ellipsometry, wettability, UV-vis spectroscopy, and atomic force microscopy (AFM). The branched multilayer films display improved stiffness, as well as a unique defect self-repair capability, attributed to cross-linking in the layers and lateral expansion over defects during multilayer growth. Transmetalation, i.e., exposure of Zr4+-based assemblies to Hf4+ ions, was used to evaluate the cross-linking. Conductive atomic force microscopy (AFM) was used to probe the electrical properties of the multilayers, revealing excellent dielectric behavior. The special properties of the branched layers were emphasized by comparison with analogous multilayers prepared similarly using linear (tetrahydroxamate) ligand molecules. The process of defect annihilation by bridging over defective areas, attributed to lateral expansion via the excess bishydroxamate groups, was demonstrated by introduction of artificial defects in the anchor monolayer, followed by assembly of two layers of either the linear or the branched molecule. Analysis of selective binding of Au nanoparticles (NPs) to unblocked defects emphasized the superior repair mechanism in the branched layers with respect to the linear ones.
Antisense and RNAi: powerful tools in drug target discovery and validation. (2003)

Drug target discovery and validation are complex processes that require significant resource investments and impose a substantial economic burden on the pharmaceutical industry. Technologies that accelerate or enhance the precision of target selection are, therefore, in high demand. Traditional antisense and RNA interference (RNAi) technologies are powerful tools with applications in multiple phases of drug target discovery and validation. These approaches elicit potent and highly selective cleavage of a target mRNA, permitting evaluation of the role of the corresponding protein based on a loss-of-function phenotype. Incorporation of these technologies into high-throughput screens, in vitro biological assays and in vivo disease models provides valuable insight into gene function. Efforts are also underway to develop these agents as drugs. This review presents recent studies involving antisense and RNAi, and discusses how these technologies are facilitating target selection at various stages of the drug development process.
Isolation of Positional Isomers of Mono-poly(ethylene glycol)ylated Interferon/α-2a and the Determination of Their Biochemical and Biological Characteristics (1997)

MonoPEGylated interferon α-2a (monoPEG-IFN) is produced by conjugating interferon α-2a to a chemically reactive form of polyethylene glycol-5000 in 1:1 ratio, via a urea linkage. Potentially, all 11 lysine residues and the N-terminal amino group in interferon α-2a are available for PEGylation. Thus monoPEG-IFN is a mixture of individual species, each having a unique site of PEGylation. A method involving sulfopropyl-high performance liquid chromatography (SP-HPLC) which exploits the minute local charge differences between the individual monoPEG-IFN α-2a species (positional isomers) is used to separate them. Eleven positional isomers were isolated by this method, each having a specific lysine as their PEGylation site indicating all eleven lysines of interferon α-2a were PEGylated. However, N-terminal amino group was not derivatized. All isolated species exhibit antiviral and antiproliferative activities.
“B27 Disease” Is a New Autoimmune Disease That Affects Millions of People (2007)

"B27 disease" is a new autoimmune disease that afflicts millions of people throughout the world. "B27 disease" occurs in individuals who have ankylosing spondylitis (AS) or preankylosing spondylitis and/or uveitis and are also positive for HLA-B27. Molecular mimicry between the bowel microbe Klebsiella and the HLA-B27 molecule, as well as the spinal collagens types I, III, and IV, indicates a pathological mechanism involving autoimmunity. Antibodies to Klebsiella microbes have been reported in AS patients from 18 different countries. Sera from patients with AS show complement-dependent cytopathic activity against sheep red cells coated with HLA-B27 peptide antigens. Diagnosis of B27 disease can lead to early treatment, involving low-starch diet, sulfasalazine, and immunosuppressive and biological agents so as to prevent the irreversible bony changes of established classical AS. The concept of B27 disease provides a new approach to the study and treatment of these disorders and needs to be evaluated in prospective studies by the world rheumatological community.
Viral Wasting Syndrome of Swine: Experimental Reproduction of Postweaning Multisystemic Wasting Syndrome in Gnotobiotic Swine by Coinfection with Porcine Circovirus 2 and Porcine Parvovirus (2000)

One-day-old gnotobiotic piglets were inoculated intranasally with in vitro passaged porcine circovirus 1 (PCV-1), PCV-2, and porcine parvovirus (PPV) alone or in combination (PCV-1/PCV-2, PCV-1/PPV, and PCV-2/PPV). Piglets were evaluated for 1) the development of porcine postweaning multisystemic wasting syndrome (PMWS), 2) distribution of viral antigens by immunochemistry, and 3) viremia and the presence of viral DNA in nasal and ocular secretions and feces. All single agent-infected piglets and piglets infected with PCV-1/PCV-2 or PCV-1/PPV were clinically asymptomatic. They were transiently viremic and seroconverted to homologous virus(es). At termination of the study on postinfection day (PID) 35, microscopic lesions were restricted to focal inflammatory cell infiltrates in livers and myocardia. One piglet given PCV-1/PPV was PPV viremic for 2 weeks after infection and had lymphangiectasia of the spiral and descending colon associated with granulomatous inflammation. All four PCV-2/PPV-inoculated piglets developed PMWS, characterized by sudden onset of depression and anorexia, icterus, and submucosal edema. One piglet became moribund on PID 27, and the remaining three piglets were euthanatized between PID 27 and PID 30 because of severe disease. Lymph nodes were small and the livers were mottled. Disseminated angiocentric granulomatous inflammation was present in all tissues examined except the brain. Multiple lightly basophilic intracytoplasmic inclusion bodies were identified in macrophages and histiocytes. PCV-2 antigen was widely distributed within macrophages; PPV antigen was sparse. Hepatocellular necrosis and bile retention were prominent. PCV-2 DNA was identified in ocular, fecal, and nasal secretions. Terminal sera contained antibodies to PPV (4/4) and PCV-2 (3/ 4). Production of PMWS in gnotobiotic swine appears to require PCV-2 and additional infectious agents such as PPV for full disease expression in gnotobiotic piglets.