gebhart/patrepeval huggingface dataset:
NMR studies on YSPTSPSY: implications for the design of DNA bisintercalators (1992)

NMR (600 MHz) studies on YSPTSPSY (1), the heptad repeat unit of RNA polymerase II with an extra tyrosine added to the N-terminus, show that the peptide is partially structured in aqueous solution. Peptide 1 contains two overlapping SPXX sequences and has been reported to bind to DNA by bisintercalation (Suzuki, M. Nature 1990, 344, 562-565). In 90% H2O solution at pH 3.2, the major species, which is present in > 90%, contains Pro3 and Pro6 in the trans conformation. At low temperature (4 degrees C), NOE connectivities are consistent with the presence of beta-turn structures in equilibrium with unfolded forms of the peptide. A strong dNN connectivity between Thr4/Ser5, a d alpha N connectivity between Pro3/Thr4, and a medium-range NOE between Pro3 alpha and Ser5 NH indicate the presence of a beta-turn formed by (i) Ser2-Pro3-Thr4-Ser5. A strong dNN connectivity between Ser7/Tyr8 and weaker dN delta NOE connectivities between Ser2/Pro3 delta and Ser7/Pro6 delta were also detected. The solution conformation of the peptide appears to have a crucial role in determining the interaction of the peptide with DNA, given that only bisintercalation has been reported in DNA-binding studies on 1 (Suzuki, M. Nature 1990, 344, 562-565). On the basis of these results, the peptide unit--SPTSPS--(3) has considerable potential as a structured linker in the preparation of DNA bisintercalators of the general structure Xaa-SPTSPS-Zaa (2) with improved selectivity properties.
The clinical significance of a positive Amnisure test™ in women with term labor with intact membranes (2009)

(1) A positive Amnisure test is present in about one-third nulliparous women at term presenting in labor with intact membranes; (2) patients with a positive Amnisure test had a shorter admission-to-delivery interval than those with a negative test.
REACTIONS OF ALLYLTIN COMPOUNDS III. ALLYLATION OF AROMATIC HALIDES WITH ALLYLTRIBUTYLTIN IN THE PRESENCE OF TETRAKIS(TRIPHENYLPHOSPHINE)PALLADIUM(O) (1977)

Abstract Catalytic allylation of aryl halides with allyltributyltin in the presence of tetrakis(triphenylphosphine)palladium(O) was investigated. The reaction with aryl bromides proceeded efficiently to yield allylbenzenes.
A Microfluidic Platform for Precision Small-volume Sample Processing and Its Use to Size Separate Biological Particles with an Acoustic Microdevice (2015)

A major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15-1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection, system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing.
SHORT-TERM SAFETY AND EFFICACY OF INTRAVITREAL BEVACIZUMAB (AVASTIN) FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION (2006)

Off-label intravitreal bevacizumab therapy for neovascular ARMD was well tolerated over 3 months with improvements in visual acuity and OCT central retinal thickness measurements. While the long-term safety and efficacy of intravitreal bevacizumab remain unknown, these short-term results suggest that intravitreal bevacizumab may be the most cost effective therapy for the treatment of neovascular ARMD.
Experimental evolution of a metabolic pathway for ethylene glycol utilization by Escherichia coli (1983)

Spontaneous mutants of Escherichia coli able to grow on ethylene glycol as a sole source of carbon and energy were obtained from mutants that could grow on propylene glycol. Attempts to obtain ethylene glycol-utilizing mutants from wild-type E. coli were unsuccessful. The two major characteristics of the ethylene glycol-utilizing mutants were (i) increased activities of propanediol oxidoreductase, an enzyme present in the parental strain (a propylene glycol-positive strain), which also converted ethylene glycol into glycolaldehyde; and (ii) constitutive synthesis of high activities of glycolaldehyde dehydrogenase, which converted glycolaldehyde to glycolate. Glycolate was metabolized via the glycolate pathway, which was present in the wild-type cells; this was indicated by the induction in ethylene glycol-grown cells of glycolate oxidase, the first enzyme in the pathway. Glycolaldehyde dehydrogenase was partially characterized as an enzyme of this new metabolic pathway in E. coli, and glycolate was identified as the product of the reaction. This enzyme used NAD and NADP as coenzymes, although the NADP-dependent activity was about 10 times lower than the NAD-dependent activity. Uptake of [14C]ethylene glycol was dependent on the presence of the enzymes capable of metabolism of ethylene glycol. Glycolaldehyde and glycolate were identified as intermediate metabolites in the pathway.
Fell‐Muir Lecture: Metalloproteinases: from demolition squad to master regulators (2010)

Two families of the Metzincin clan of metalloproteinases, the matrix metalloproteinases and the disintegrin metalloproteinases have attracted much attention as important effectors of cellular interactions with their environment. They appear to play significant roles in the modulation of components of the extracellular matrix, matrix and cell receptors, as well as the cytokines and growth factors and their receptors. Such functions at the 'cutting edge' of cell biology puts these enzymes in pivotal roles in the orchestration of the rapid response of cells to their environment, acting as key switches between different signalling pathways. Inevitably such enzymes should be regarded as suitable targets for therapeutic approaches to many diseases where such pathways become dysregulated. A major challenge to the development of direct inhibitors of catalysis has been the broad structural similarity of the Metzincin catalytic site. More detailed knowledge of active site structures has helped to some extent to resolve the development of more specific chemical inhibitors and selected enzymes are now being targeted. An alternative strategy is the consideration of the role of the extracatalytic domains that are determinants of specificity at a variety of levels. Dissecting the relationships between structure and function of these interaction sites is allowing the development of new approaches to inhibition of enzyme function. Antibodies are proving useful tools in this respect and may pave the way to a novel biologics approach to disease therapy.
Detection and partial characterization of an inhibitor of plasminogen activator in human platelets. (1984)

In this study, we demonstrate the presence of a previously undescribed fibrinolytic inhibitor in human serum. It has an apparent molecular weight of 50,000 and is not detected in serum derived from platelet-poor plasma, suggesting that it originates from platelets. This conclusion is supported by a number of observations. For example, extracts of washed, gel-filtered human platelets contain an inhibitor of similar activity and size, and physiological concentrations of thrombin induce its release from the platelets. Moreover, the kinetics and dose dependency of this release are similar to those observed for the release of platelet factor 4, and the release of both molecules is blocked by pretreating the platelets with prostaglandin E1 and theophylline. Mixing experiments, which were devised to investigate the specificity of the inhibitor, showed that the fibrinolytic activity initiated by both urokinase and tissue-type plasminogen activator was blocked by platelet releasate in a dose-dependent manner. In both cases, the amount of inhibition increased when the releasates were preincubated with the purified activators, indicating a direct interaction between the activators and an inhibitor(s). The inhibitory activity was removed by preincubating the releasates with antiserum prepared against an antiactivator purified from cultured bovine aortic endothelial cells. These results indicate that platelets contain an inhibitor which is released by thrombin, inhibits both urokinase and tissue-type plasminogen activator, and is immunologically similar to an inhibitor produced by endothelial cells. This molecule may represent a new class of inhibitors, the antiactivators, which function together with alpha 2-antiplasmin to regulate the fibrinolytic system of the blood. Its release from platelets by thrombin may protect the growing thrombus against premature dissolution initiated by plasminogen activators released by the endothelium.
Fast evolving 18S rRNA sequences from Solenogastres (Mollusca) resist standard PCR amplification and give new insights into mollusk substitution rate heterogeneity (2010)

The extreme morphological diversity of mollusks is mirrored in the molecular 18S data and shows elevated substitution rates mainly in three higher taxa: true limpets (Patellogastropoda), Cephalopoda and Solenogastres. Our phylogenetic tree based on 123 species, including representatives of all mollusk classes, shows limited resolution at the class level but illustrates the pitfalls of artificial groupings formed due to shared biased sequence composition.
An African swine fever virus gene with similarity to the proto-oncogene bcl-2 and the Epstein-Barr virus gene BHRF1 (1993)

An open reading frame, LMW5-HL, in the African swine fever virus genome displays a high degree of similarity to the proto-oncogene bcl-2 and, to a lesser degree, the Epstein-Barr virus gene BHRF1. A highly conserved central region is found in all three proteins. LMW5-HL encodes a protein of 18 kDa that is present in infected porcine macrophages at both early and late times postinfection. The similarity of LMW5-HL to bcl-2 and BHRF1 suggests a role for it in cell maintenance during productive or persistent viral infection.
Overexpression of Macrophage Colony-stimulating Factor Receptor on Microglial Cells Induces an Inflammatory Response (2001)

Microglia are important in the inflammatory response in Alzheimer's disease (AD). We showed previously that macrophage colony-stimulating factor receptor (M-CSFR), encoded by the c-fms protooncogene, is overexpressed on microglia surrounding amyloid beta (Abeta) deposits in the APP(V717F) mouse model for AD. The M-CSFR is also increased on microglia after experimental brain injury and in AD. To determine the relevance of these findings, we transiently expressed M-CSFR on murine BV-2 and human SV-A3 microglial cell lines using an SV40-promoted c-fms construct. M-CSFR overexpression resulted in microglial proliferation and increased expression of inducible nitric-oxide synthase, the proinflammatory cytokines interleukin-1alpha, macrophage inflammatory protein 1-alpha, and interleukin-6 and of macrophage colony-stimulating factor (M-CSF) itself. Antibody neutralization of M-CSF showed that the M-CSFR-induced proinflammatory response was dependent on M-CSF in the culture media. By using a co-culture of c-fms-transfected murine microglia and rat organotypic hippocampal slices and a species-specific real time reverse transcriptase-polymerase chain reaction assay and enzyme-linked immunosorbent assay, we showed that M-CSFR overexpression on exogenous microglia induced expression of interleukin-1alpha by the organotypic culture. These results show that increased M-CSFR expression induces microglial proliferation, cytokine expression, and a paracrine inflammatory response, suggesting that in APP(V717F) mice increased M-CSFR on microglia could be an important factor in Abeta-induced inflammatory response.
Viral Persistence: HIV's Strategies of Immune System Evasion (2002)

▪ Abstract In contrast to most animal viruses, infection with the human and simian immunodeficiency viruses results in prolonged, continuous viral replication in the infected host. Remarkably, viral persistence is not thwarted by the presence of apparently vigorous, virus-specific immune responses. Several factors are thought to contribute to persistent viral replication, most notably the destruction of virus-specific T helper cells, the emergence of antigenic escape variants, and the expression of an envelope complex that structurally minimizes antibody access to conserved epitopes. Not as well understood, though potentially important, is the ability of at least one viral encoded protein (Nef) to prevent presentation of viral antigens in the context of major histocompatibility complex. The future success of antiviral therapies and vaccination strategies may depend largely on understanding how and to what degree each of these factors (and presumably others) contributes to immune evasion.
Cloning and Expression of a Receptor for an Insecticidal Toxin of Bacillus thuringiensis (1995)

Environmentally friendly toxins of Bacillus thuringiensis are effective in controlling agriculturally and biomedically harmful insects. However, little is known about the insect receptor molecules that bind these toxins and the mechanism of insecticidal activity. We report here for the first time the cloning and expression of a cDNA that encodes a receptor (BT-R1) of the tobacco hornworm Manduca sexta for an insecticidal toxin of B. thuringiensis. The receptor is a 210-kDa membrane glycoprotein that specifically binds the cryIA(b) toxin of B. thuringiensis subsp. berliner and leads to death of the hornworm. BT-R1 shares sequence similarity with the cadherin superfamily of proteins.
Synthesis and Dopamine Receptor Modulating Activity of Substituted Bicyclic Thiazolidine Lactam Peptidomimetics of l-Prolyl-l-leucyl-glycinamide (1999)

6-Substituted bicyclic thiazolidine lactam peptidomimetics of Pro-Leu-Gly-NH(2) (1) were synthesized to test the hypothesis that incorporation of a hydrophobic side chain into the bicyclic thiazolidine lactam scaffold would further enhance the dopamine receptor modulating activity of such peptidomimetics. The substituents employed were the isobutyl, butyl, and benzyl groups to give peptidomimetics 3-5, respectively. These peptidomimetics were evaluated in vivo as modulators of apomorphine-induced rotational behavior in the 6-hydroxydopamine-lesioned rat model of hemiparkinsonism and were compared with the unsubstituted bicyclic thiazolidine lactam Pro-Leu-Gly-NH(2) peptidomimetic 2. Peptidomimetics 3-5 each affected rotational behavior in a bell-shaped dose-response relationship producing maximal increases of 44% (1 microgram/kg,ip), 56% (0.1 microgram/kg,ip), and 30% (1 microgram/kg, ip), respectively. In comparison, unsubstituted peptidomimetic 2 increased rotational behavior by only 23% at a dose of 0.1 microgram/kg, ip.
Targeting HER2-Positive Breast Cancer with Trastuzumab-DM1, an Antibody–Cytotoxic Drug Conjugate (2008)

HER2 is a validated target in breast cancer therapy. Two drugs are currently approved for HER2-positive breast cancer: trastuzumab (Herceptin), introduced in 1998, and lapatinib (Tykerb), in 2007. Despite these advances, some patients progress through therapy and succumb to their disease. A variation on antibody-targeted therapy is utilization of antibodies to deliver cytotoxic agents specifically to antigen-expressing tumors. We determined in vitro and in vivo efficacy, pharmacokinetics, and toxicity of trastuzumab-maytansinoid (microtubule-depolymerizing agents) conjugates using disulfide and thioether linkers. Antiproliferative effects of trastuzumab-maytansinoid conjugates were evaluated on cultured normal and tumor cells. In vivo activity was determined in mouse breast cancer models, and toxicity was assessed in rats as measured by body weight loss. Surprisingly, trastuzumab linked to DM1 through a nonreducible thioether linkage (SMCC), displayed superior activity compared with unconjugated trastuzumab or trastuzumab linked to other maytansinoids through disulfide linkers. Serum concentrations of trastuzumab-MCC-DM1 remained elevated compared with other conjugates, and toxicity in rats was negligible compared with free DM1 or trastuzumab linked to DM1 through a reducible linker. Potent activity was observed on all HER2-overexpressing tumor cells, whereas nontransformed cells and tumor cell lines with normal HER2 expression were unaffected. In addition, trastuzumab-DM1 was active on HER2-overexpressing, trastuzumab-refractory tumors. In summary, trastuzumab-DM1 shows greater activity compared with nonconjugated trastuzumab while maintaining selectivity for HER2-overexpressing tumor cells. Because trastuzumab linked to DM1 through a nonreducible linker offers improved efficacy and pharmacokinetics and reduced toxicity over the reducible disulfide linkers evaluated, trastuzumab-MCC-DM1 was selected for clinical development.
Effects of distributed energy resources on conservation voltage reduction (CVR) (2011)

Conservation voltage reduction (CVR) is one of the cheapest technologies that can be intelligently leveraged to provide considerable energy savings. The addition of renewables in the form of distributed resources can affect the entire power system, but more importantly, affects the traditional substation control schemes at the distribution level. This paper looks at the effect on energy consumption, peak load reduction, and voltage profile changes caused but the addition of distributed generation in a distribution feeder using a volt-var control (VVC) technique for CVR with different end-of-line (EOL) measurements. An IEEE 13-node system is used to simulate the various cases. Energy savings and peak load reduction for different simulation scenarios are compared.
Chronic inflammation and oxidative stress in human carcinogenesis (2007)

A wide array of chronic inflammatory conditions predispose susceptible cells to neoplastic transformation. In general, the longer the inflammation persists, the higher the risk of cancer. A mutated cell is a sine qua non for carcinogenesis. Inflammatory processes may induce DNA mutations in cells via oxidative/nitrosative stress. This condition occurs when the generation of free radicals and active intermediates in a system exceeds the system's ability to neutralize and eliminate them. Inflammatory cells and cancer cells themselves produce free radicals and soluble mediators such as metabolites of arachidonic acid, cytokines and chemokines, which act by further producing reactive species. These, in turn, strongly recruit inflammatory cells in a vicious circle. Reactive intermediates of oxygen and nitrogen may directly oxidize DNA, or may interfere with mechanisms of DNA repair. These reactive substances may also rapidly react with proteins, carbohydrates and lipids, and the derivative products may induce a high perturbation in the intracellular and intercellular homeostasis, until DNA mutation. The main substances that link inflammation to cancer via oxidative/nitrosative stress are prostaglandins and cytokines. The effectors are represented by an imbalance between pro-oxidant and antioxidant enzyme activities (lipoxygenase, cyclooxygenase and phospholipid hydroperoxide glutathione-peroxidase), hydroperoxides and lipoperoxides, aldehydes and peroxinitrite. This review focalizes some of these intricate events by discussing the relationships occurring among oxidative/nitrosative/metabolic stress, inflammation and cancer.
An N-Linked Glycosylation Motif from the Noncleaving Luteinizing Hormone Receptor Substituted for the Homologous Region (Gly367 to Glu369) of the Thyrotropin Receptor Prevents Cleavage at Its Second, Downstream Site (1997)

The thyrotropin receptor (TSHR) exists in two forms (single polypeptide and two subunits), whereas the lutropin/chorionic gonadotropin receptor (LH/CGR) is a single chain. Recent data suggest that the TSHR cleaves at two sites. We mutagenized selected chimeric TSH-LH/CGR to localize the cleavage sites in the TSHR. All 23 receptors mutated in the estimated vicinity of the upstream site cleaved into two subunits as determined by 125I-TSH cross-linking to intact cells. In contrast, in a series of mutations homologous to the noncleaving LH/CGR, the downstream TSHR cleavage site localized to three amino acids (GQE367-369). Remarkably, group substitution of these residues, but not substitution of individual residues, abolished cleavage. Moreover, the mutation that prevented cleavage (GQE367-369NET) transposed a motif (NET291-293) that is glycosylated in the LH/CGR. TSHR cleavage or noncleavage after substitution of GQE367-369 with other triplets (AAA, NQE, and NQT) was consistent with a role for N-linked glycosylation at this site. In summary, our data (i) support the concept that the TSHR cleaves at two sites, (ii) relate TSHR residues GQE367-369 to cleavage at the second, downstream site, and (iii) suggest that cleavage or noncleavage at site two is related to N-linked glycosylation. These findings provide new insight into the evolutionary divergence of two closely related receptors.
Deep learning-based virtual histology staining using auto-fluorescence of label-free tissue (2018)

Histological analysis of tissue samples is one of the most widely used methods for disease diagnosis. After taking a sample from a patient, it goes through a lengthy and laborious preparation, which stains the tissue to visualize different histological features under a microscope. Here, we demonstrate a label-free approach to create a virtually-stained microscopic image using a single wide-field auto-fluorescence image of an unlabeled tissue sample, bypassing the standard histochemical staining process, saving time and cost. This method is based on deep learning, and uses a convolutional neural network trained using a generative adversarial network model to transform an auto-fluorescence image of an unlabeled tissue section into an image that is equivalent to the bright-field image of the stained-version of the same sample. We validated this method by successfully creating virtually-stained microscopic images of human tissue samples, including sections of salivary gland, thyroid, kidney, liver and lung tissue, also covering three different stains. This label-free virtual-staining method eliminates cumbersome and costly histochemical staining procedures, and would significantly simplify tissue preparation in pathology and histology fields.
THE MECHANICAL PROPERTIES OF SINTERED LOW-ALLOY STEELS (1962)

An unacceptable degree of scatter in the values obtained in tensile tests of sintered parts may occur if their elongation does not exceed a few percent. To ensure the required elongation, the composition of the material selected must correspond to that of alloys made by melting which exhibit a certain minimum elongation in the forged and annealed condition. This minimum is a function of the density of the sintered compact and a knowledge of its value can be of assistance in choosing the correct composition. Values of Young’s modulus, Poisson’s ratio, and impact-resistance are also given as a function of density.