gebhart/patrepeval huggingface dataset:
Identification of targets of leptin action in rat hypothalamus. (1996)

The hypothesis that leptin (OB protein) acts in the hypothalamus to reduce food intake and body weight is based primarily on evidence from leptin-deficient, ob/ob mice. To investigate whether leptin exerts similar effects in normal animals, we administered leptin intracerebroventricularly (icv) to Long-Evans rats. Leptin administration (3.5 microg icv) at the onset of nocturnal feeding reduced food intake by 50% at 1 h and by 42% at 4 h, as compared with vehicle-treated controls (both P < 0.05). To investigate the basis for this effect, we used in situ hybridization (ISH) to determine whether leptin alters expression of hypothalamic neuropeptides involved in energy homeostasis. Two injections of leptin (3.5 microg icv) during a 40 h fast significantly decreased levels of mRNA for neuropeptide Y (NPY, which stimulates food intake) in the arcuate nucleus (-24%) and increased levels of mRNA for corticotrophin releasing hormone (CRH, an inhibitor of food intake) in the paraventricular nucleus (by 38%) (both P < 0.05 vs. vehicle-treated controls). To investigate the anatomic basis for these effects, we measured leptin receptor gene expression in rat brain by ISH using a probe complementary to mRNA for all leptin receptor splice variants. Leptin receptor mRNA was densely concentrated in the arcuate nucleus, with lower levels present in the ventromedial and dorsomedial hypothalamic nuclei and other brain areas involved in energy balance. These findings suggest that leptin action in rat hypothalamus involves altered expression of key neuropeptide genes, and implicate leptin in the hypothalamic response to fasting.
Structural and functional relations among thioredoxins of different species (1991)

Three-dimensional models have been constructed of homologous thioredoxins and protein disulfide isomerases based on the high resolution x-ray crystallographic structure of the oxidized form of Escherichia coli thioredoxin. The thioredoxins, from archebacteria to humans, have 27-69% sequence identity to E. coli thioredoxin. The models indicate that all the proteins have similar three-dimensional structures despite the large variation in amino acid sequences. As expected, residues in the active site region of thioredoxins are highly conserved. These include Asp-26, Ala-29, Trp-31, Cys-32, Gly-33, Pro-34, Cys-35, Asp-61, Pro-76, and Gly-92. Similar residues occur in most protein disulfide isomerase sequences. Most of these residues form the surface around the active site that appears to facilitate interactions with other enzymes. Other structurally important residues are also conserved. A proline at position 40 causes a kink in the alpha-2 helix and thus provides the proper position of the active site residues at the amino end of this helix. Pro-76 is important in maintaining the native structure of the molecule. In addition, residues forming the internal contact surfaces between the secondary structural elements are generally unchanged such as Phe-12, Val-25, and Phe-27.
Synthesis and biological activity of 5-amino- and 5-hydroxyquinolones, and the overwhelming influence of the remote N1-substituent in determining the structure-activity relationship (1991)

A series of 5-amino- and 5-hydroxyquinolone antibacterials substituted at C7 with a select group of common piperazinyl and 3-aminopyrrolidinyl side chains was prepared. These 5-substituted derivatives were compared to the analogous 5-hydrogen compounds for antiinfective activity by using DNA gyrase inhibition, minimum inhibitory concentrations against a variety of bacteria, and in vivo efficacy in the mouse infection model. The influence on the structure-activity relationships of varied substituents at C8 (H, F, Cl) and N1 (ethyl, cyclopropyl, difluorophenyl) was also studied. The results showed that several of the structure-activity conclusions regarding side-chain bulk at C7, the effect of halogen at C8, and the effect of the C5-amino group were greatly influenced by the choice of the N1-substituent. Several outstanding broad spectrum quinolones were identified in this work. In particular, the spectrum and potency of the 7-piperazinyl quinolones could be greatly enhanced by the judicious choice of C5-, C8-, and N1-substituents.
The Impact of Brand Equity and the Company's Reputation on Revenues (2001)

Abstract This paper intends to establish the relationships among variables in corporate communications, especially between advertising and public relations, and to form an evaluation model for integrating the effects of brand equity and the company's reputation in the context of integrated marketing communications (IMC). A new approach for integrating the effects of brand equity and the company's reputation was introduced and the IMC evaluation model was specified for testing. The proposed model was tested with existing secondary data. The outcomes indicated that both brand equity and the company's reputation have significant impact on revenues and showed the positive relationship between brand equity and the company's reputation in the proposed model to justify the need of IMC in overall corporate communications. Key Words: Advertisingbrand equitycorporate communicationsevaluationintegrated marketing communications (IMC)public relationsreputation management
Evaluation of the FLEXX incremental construction algorithm for protein-ligand docking (1999)

We report on a test of FLEXX, a fully automatic docking tool for flexible ligands, on a highly diverse data set of 200 protein-ligand complexes from the Protein Data Bank. In total 46.5% of the complexes of the data set can be reproduced by a FLEXX docking solution at rank 1 with an rms deviation (RMSD) from the observed structure of less than 2 . This rate rises to 70% if one looks at the entire generated solution set. FLEXX produces reliable results for ligands with up to 15 components which can be docked in 80% of the cases with acceptable accuracy. Ligands with more than 15 components tend to generate wrong solutions more often. The average runtime of FLEXX on this test set is 93 seconds per complex on a SUN Ultra-30 workstation. In addition, we report on ''cross-docking'' experiments, in which several receptor structures of complexes with identical proteins have been used for docking all cocrystallized ligands of these complexes. In most cases, these experiments show that FLEXX can acceptably dock a ligand into a foreign receptor structure. Finally we report on screening runs of ligands out of a library with 556 entries against ten different proteins. In eight cases FLEXX is able to find the original inhibitor within the top 7% of the total library.
Design and Development of Supersaturatable Self-Emulsifying Drug Delivery Systems for Enhancing the Gastrointestinal Absorption of Poorly Soluble Drugs (2007)

Ping Gao Small Molecule Pharmaceutics, Amgen, Inc., Thousand Oaks, California, U.S.A.Walter Morozowich Prodrug/Formulation Consultant, Kalamazoo, Michigan, U.S.A.INTRODUCTIONBackground on Conventional Self-Emulsifying Drug Delivery Systems and the Supersaturatable FormulationsLow water solubility is widely recognized as the main reason for the poor oral absorption of many new chemical entities. Conventional solubilization approaches such as salt formation, cosolvents and, more recently, surfactant-based micellar systems, are now widely employed in enhancing the oral absorption of drugs, primarily poorly soluble drugs. In particular, self-emulsifying drug delivery systems (SEDDS) are commonly employed in improving the oral exposure of poorly soluble, lipophilic drugs (1-5). However, a high surfactant level is needed in the conventional SEDDS formulations in order to prevent precipitation of the drug on dilution with water in the gastrointestinal (GI) tract. The surfactants that are commonly employed in SEDDS formulations can increase the incidence ofGI side-effects (6,7) and, therefore, a reduced amount of surfactant in the formulations should minimize the surfactant-induced GI side-effects (8-10).
Prediction of the Outcome of Rhesus Haemolytic Disease of the Newborn: Additional Information Using an ADCC Assay (1984)

An in vitro test system is described which measures the ability of anti-D sera to lyse Rh(D)-positive red cells. This test was applied to anti-D sera from 11 cases of HDN selected in Glasgow and tested 'blind' in Edinburgh. Evidence is presented to support the view that the ADCC (antibody-dependent cell-mediated cytotoxicity ) assay can correctly identify those cases where there is a satisfactory clinical outcome despite a high level of anti-D suggesting otherwise. Amniocentesis might therefore be avoided in this group.
Atypical Kunitz-Type Serine Proteinase Inhibitors Produced by the Ruminant Placenta1 (2004)

Recently, an unusual family of genes was identified with expression confined to the trophoblast of ruminant ungulate species. The members of this family (the trophoblast Kunitz domain proteins, or TKDPs) are characterized by the presence of one or more similar, approximately 80-residue repeat sequences placed ahead of a Kunitz serine proteinase-inhibitor domain. To examine the specificity of the Kunitz moiety, the Kunitz domains of selected TKDPs and a control Kunitz protein, bovine pancreatic trypsin inhibitor (BPTI), were produced as glutathione S-transferase fusions, and their abilities to inhibit six serine proteinases were examined. Circular dichroism spectroscopy confirmed that the Kunitz fold was intact. Three of the TKDPs had unusual residues at their P1 "warhead" (ovine TKDP-1, Asn; bovine TKDP-3, Thr; and bovine TKDP-5, Ile) and exhibited no measurable inhibitory activity toward any of the proteinases. Three (ovine TKDP-3, bovine TKDP-3, and bovine TKDP-4) lacked the conserved cysteines at residues 14 and 38 that form one of the highly conserved disulfide bonds that are structurally important in all known mammalian Kunitz proteins. Ovine TKDP-3 and bovine TKDP-4 had P1 lysines and inhibited trypsin and plasmin with K(i) values only approximately 10-fold higher than that of BPTI. Bovine TKDP-2 had a P1 lysine and the three conserved disulfides, but it possessed an unusual residue (Asp) at P2. It exhibited no inhibitory activity. These data suggest that the function of the TKDP, like certain Kunitz proteins found in snake venoms, may not be in proteinase inhibition.
Electron Beam Projection Nanopatterning Using Crystal Lattice Images Obtained from High Resolution Transmission Electron Microscopy (2007)

An electron beam projection lithography technique that employs the various crystalline lattice images available in high-resolution transmission electron microscopy is reported. We successfully fabricated periodic arrays of various patterned structures with feature sizes of about 25 nm using single-crystalline Si and β-Si3N4 as the mask materials.
Nonvirus-associated antigens in virus-induced mouse mammary tumors. (1968)

Summary Common, cross-reacting virus-associated tumor antigens have been demonstrated by many workers in most virus-induced experimental tumor systems, including mammary tumors induced by the mouse mammary tumor virus (MTV). By the use of mice neonatally infected with the MTV and therefore immunologically tolerant of this virus and its associated antigens, other antigens have now been detected in MTV-induced tumors which do not cross-react and which, accordingly, are probably not related directly to the inducing virus. The immunogenicity of 23 spontaneous mouse mammary carcinomas was tested in MTV-infected C3H hosts. The immunization procedure consisted of subcutaneous implantation of living tumor tissue. The challenge was with suspensions of living tumor cells at the time of removal of the immunizing grafts. Immunity was manifested by rejection of the challenge implants by a high proportion of the presensitized hosts. Of the 23 tumors, 5 were found to induce high resistance to challenge in repeated tests. It is concluded that nonvirusassociated antigens are found in some C3H mammary carcinomas. Histologic studies showed that presensitization resulted in lymphocytic invasion of challenge implants of tumor tissue. Immunity to tumor-cell implants was adoptively transferred to C3H recipients with lymphocytes from sensitized C3Hf donors. Four of the immunogenic tumors were tested for cross-immunization in C3H mice. In one test reciprocal cross-reactivity was found between two tumors. In 3 tests involving the remaining two and one of the former tumors, no cross-reactivity was detected. All 4 tumors cross-reacted in MTV-free C3Hf mice. These findings, together with other evidence, show that mouse mammary tumors contain a common component which is immunogenic in the MTV-free C3Hf mice but not in the MTV-infected C3H mice. In addition, some tumors contain tumor-specific antigens which are unrelated to the MTV and which make them immunogenic in the MTV-infected C3H mice.
Synthesis, Improved Antisense Activity and Structural Rationale for the Divergent RNA Affinities of 3′-Fluoro Hexitol Nucleic Acid (FHNA and Ara-FHNA) Modified Oligonucleotides (2011)

The synthesis, biophysical, structural, and biological properties of both isomers of 3'-fluoro hexitol nucleic acid (FHNA and Ara-FHNA) modified oligonucleotides are reported. Synthesis of the FHNA and Ara-FHNA thymine phosphoramidites was efficiently accomplished starting from known sugar precursors. Optimal RNA affinities were observed with a 3'-fluorine atom and nucleobase in a trans-diaxial orientation. The Ara-FHNA analog with an equatorial fluorine was found to be destabilizing. However, the magnitude of destabilization was sequence-dependent. Thus, the loss of stability is sharply reduced when Ara-FHNA residues were inserted at pyrimidine-purine (Py-Pu) steps compared to placement within a stretch of pyrimidines (Py-Py). Crystal structures of A-type DNA duplexes modified with either monomer provide a rationalization for the opposing stability effects and point to a steric origin of the destabilization caused by the Ara-FHNA analog. The sequence dependent effect can be explained by the formation of an internucleotide C-F···H-C pseudo hydrogen bond between F3' of Ara-FHNA and C8-H of the nucleobase from the 3'-adjacent adenosine that is absent at Py-Py steps. In animal experiments, FHNA-modified antisense oligonucleotides formulated in saline showed a potent downregulation of gene expression in liver tissue without producing hepatotoxicity. Our data establish FHNA as a useful modification for antisense therapeutics and also confirm the stabilizing influence of F(Py)···H-C(Pu) pseudo hydrogen bonds in nucleic acid structures.
RANSAC for motion-distorted 3D visual sensors (2013)

Visual odometry (VO) is a highly efficient and powerful 6D motion estimation technique; state-of-the-art bundle adjustment algorithms now optimize over several frames of temporally tracked, appearance-based features in real time. It is well known that the temporal feature correspondence process is highly prone to mismatches. The standard technique used for outlier rejection in this process is random sample consensus (RANSAC), which is an iterative and non-deterministic process used to find the parameters of a mathematical model that best describe a likely set of inliers. The traditional model used for RANSAC in the visual odometry pipeline is a rigid transformation between two camera poses; this model has long assumed the use of an imaging sensor with a global shutter. In order to use imaging sensors that do not operate with a global shutter, it is proposed that the RANSAC algorithm be modified to use a constant-camera-velocity model. Specifically, this paper investigates the use of a two-axis scanning lidar in the visual-odometry pipeline. Images are formed using lidar intensity data, and due to the scanning-while-moving nature of the lidar, the behaviour of the sensor resembles that of a slow rolling-shutter camera. We formulate a Motion-Compensated RANSAC algorithm that uses a constant-velocity model and the individual timestamp of each extracted feature. The algorithm is validated using 6880 lidar frames with a resolution of 480 × 360, captured at 2 Hz, over a 1.1 km traversal. Our results show that the new algorithm results in far more inlying feature tracks for rolling-shutter-type images and ultimately higher-accuracy VO results.
Highly Practical Copper(I)/TEMPO Catalyst System for Chemoselective Aerobic Oxidation of Primary Alcohols (2011)

Aerobic oxidation reactions have been the focus of considerable attention, but their use in mainstream organic chemistry has been constrained by limitations in their synthetic scope and by practical factors, such as the use of pure O(2) as the oxidant or complex catalyst synthesis. Here, we report a new (bpy)Cu(I)/TEMPO catalyst system that enables efficient and selective aerobic oxidation of a broad range of primary alcohols, including allylic, benzylic, and aliphatic derivatives, to the corresponding aldehydes using readily available reagents, at room temperature with ambient air as the oxidant. The catalyst system is compatible with a wide range of functional groups and the high selectivity for 1° alcohols enables selective oxidation of diols that lack protecting groups.
Promoting the young child's development in the intensive care unit. (1989)

Young children are much more emotionally vulnerable to hospitalization than are adults. The admission of a child to an intensive care unit (ICU) is stress-producing and can affect the child's ability to develop at an optimal level. This article provides the ICU nurse with a working knowledge of normal growth and developmental patterns of infants and toddlers. Internal strengths of the child, external supports, and environmental manipulation that the nurse can use to promote the critically ill child's growth and development and support the child in coping with hospitalization are presented. Discussion centers on the child experiencing an acute crisis that requires long-term intensive monitoring, rather than on the chronically ill child.
Features of gold having micrometer to centimeter dimensions can be formed through a combination of stamping with an elastomeric stamp and an alkanethiol ‘‘ink’’ followed by chemical etching (1993)

This letter describes a technique that can be used to produce well-defined features of gold. The technique involves patterning of a self-assembled monolayer (SAM) on a gold substrate using an elastomer stamp (fabricated either from a phenol-formaldehyde polymer or polydimethylsiloxane), followed by selective etching in an aqueous, basic solution of cyanide ion and dissolved dioxygen (1M KOH, 0.1 M KCN). Electrically conductive structures of gold with dimensions as small as 1 μm have been produced using this procedure. Once a rubber stamp is fabricated, patterning and etching of gold substrates is straightforward. This method is convenient, does not require routine access to clean rooms and photolithographic equipment, and can be used to produce multiple copies of a pattern.
Prevention of airway inflammation with topical cream containing imiquimod and small interfering RNA for natriuretic peptide receptor (2008)

These results demonstrate that topical cream containing imiquimod and siNPRA nanoparticles exerts an anti-inflammatory effect and may provide a new and simple therapy for asthma.
Efficacy of the anti–IL-6 receptor antibody tocilizumab in neuromyelitis optica (2014)

This study provides Class IV evidence that in patients with NMO, TCZ reduces relapse rate, neuropathic pain, and fatigue.
Ketamine-Induced Apoptosis in Normal Human Urothelial Cells (2016)

Recreational abuse of ketamine has been associated with the emergence of a new bladder pain syndrome, ketamine-induced cystitis, characterized by chronic inflammation and urothelial ulceration. We investigated the direct effects of ketamine on normal human urothelium maintained in organ culture or as finite cell lines in vitro. Exposure of urothelium to ketamine resulted in apoptosis, with cytochrome c release from mitochondria and significant subsequent caspase 9 and 3/7 activation. The anesthetic mode-of-action for ketamine is mediated primarily through N-methyl d-aspartate receptor (NMDAR) antagonism; however, normal (nonimmortalized) human urothelial cells were unresponsive to NMDAR agonists or antagonists, and no expression of NMDAR transcript was detected. Exposure to noncytotoxic concentrations of ketamine (≤1 mmol/L) induced rapid release of ATP, which activated purinergic P2Y receptors and stimulated the inositol trisphosphate receptor to provoke transient release of calcium from the endoplasmic reticulum into the cytosol. Ketamine concentrations >1 mmol/L were cytotoxic and provoked a larger-amplitude increase in cytosolic Ca(2+) concentration that was unresolved. The sustained elevation in cytosolic Ca(2+) concentration was associated with pathological mitochondrial oxygen consumption and ATP deficiency. Damage to the urinary barrier initiates bladder pain and, in ketamine-induced cystitis, loss of urothelium from large areas of the bladder wall is a reported feature. This study offers first evidence for a mechanism of direct toxicity of ketamine to urothelial cells by activating the intrinsic apoptotic pathway.
CDART: Protein Homology by Domain Architecture (2002)

The Conserved Domain Architecture Retrieval Tool (CDART) performs similarity searches of the NCBI Entrez Protein Database based on domain architecture, defined as the sequential order of conserved domains in proteins. The algorithm finds protein similarities across significant evolutionary distances using sensitive protein domain profiles rather than by direct sequence similarity. Proteins similar to a query protein are grouped and scored by architecture. Relying on domain profiles allows CDART to be fast, and, because it relies on annotated functional domains, informative. Domain profiles are derived from several collections of domain definitions that include functional annotation. Searches can be further refined by taxonomy and by selecting domains of interest. CDART is available at http://www.ncbi.nlm.nih.gov/Structure/lexington/lexington.cgi.
Ossification of the Posterior Longitudinal Ligament: An Update on Its Biology, Epidemiology, and Natural History (2006)

Significant progress has been achieved in basic research during the past decade on the pathogenesis of ossification of the posterior longitudinal ligament (OPLL), a multifactorial disease in which complex genetic and environmental factors interact. A review of the literature was conducted to update recent findings on the biology, epidemiology, natural history, and related diseases of OPLL. Gene analysis studies found specific polymorphisms that may be associated with OPLL in several collagen genes, which encode for extracellular matrix proteins. Polymorphisms in the nucleotide pyrophosphate gene, which is involved in regulation of calcification in chondrocytes, may also be associated with OPLL. However, the results of the gene analysis studies have not always been consistent. Involvement of many growth factors and cytokines, including bone morphogenic proteins and transforming growth factor-beta, has been demonstrated in various histochemical and cytochemical analyses. Several transcription factors involved in cellular differentiation may also have a role. Recent epidemiological studies reaffirmed an earlier finding that diabetes mellitus is a distinct risk factor for OPLL. The long-term follow-up studies of OPLL patients are disclosing the natural history, as well as the frequency and rate of progression, of OPLL after surgical intervention. Further knowledge on the factors responsible for progression of OPLL may predict its behavior in each patient, and treatment may be tailored accordingly. The coexistence of OPLL with other diseases of ectopic ossification of the spine, such as ossification of the ligamentum flavum and diffuse idiopathic skeletal hyperostosis, is not uncommon. Scientific breakthrough in those diseases may, in turn, give insights into the pathogenesis of OPLL.