gebhart/patrepeval huggingface dataset:
YOUNG PLANETARY NEBULAE:HUBBLE SPACE TELESCOPEIMAGING AND A NEW MORPHOLOGICAL CLASSIFICATION SYSTEM (2011)

Using Hubble Space Telescope images of 119 young planetary nebulae, most of which have not previously been published, we have devised a comprehensive morphological classification system for these objects. This system generalizes a recently devised system for pre-planetary nebulae, which are the immediate progenitors of planetary nebulae (PNs). Unlike previous classification studies, we have focussed primarily on young PNs rather than all PNs, because the former best show the influences or symmetries imposed on them by the dominant physical processes operating at the first and primary stage of the shaping process. Older PNs develop instabilities, interact with the ambient interstellar medium, and are subject to the passage of photoionization fronts, all of which obscure the underlying symmetries and geometries imposed early on. Our classification system is designed to suffer minimal prejudice regarding the underlying physical causes of the different shapes and structures seen in our PN sample, however, in many cases, physical causes are readily suggested by the geometry, along with the kinematics that have been measured in some systems. Secondary characteristics in our system such as ansae indicate the impact of a jet upon a slower-moving, prior wind; a waist is the signature of a strong equatorial concentration of matter, whether it be outflowing or in a bound Keplerian disk, and point symmetry indicates a secular trend, presumably precession, in the orientation of the central driver of a rapid, collimated outflow.
Natriuretic Peptides (2003)

Cardiac natriuretic peptides are a family of structurally related peptides that are important in sodium and volume homeostasis. They consist of atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide and are elevated in patients with left ventricular dysfunction. In contrast with vasoconstrictive hormones, such as norepinephrine, angiotensin II, and arginine vasopressin, which worsen the physiological milieu in patients with left ventricular dysfunction and heart failure, the natriuretic peptides ameliorate these effects by promoting natriuresis, diuresis, peripheral vasodilation, and by inhibiting the renin-angiotensin system. The serum levels of the natriuretic peptides correlate with the severity of heart failure and appear to have prognostic value. The present article reviews the biochemistry, molecular biology, and physiology of natriuretic peptides and their pathophysiological link to heart failure. The therapeutic uses of natriuretic peptides are also reviewed. This includes the use of intravenous nesiritide, a synthetic human brain natriuretic peptide, and the recently developed vasopeptidase inhibitors which are designed to inhibit the degradation of natriuretic peptides.
A brief history of antidepressant drug development: from tricyclics to beyond ketamine (2018)

Firstly, we review how the pharmacological treatment for major depression started, and we point out the main drugs discovered, the researchers involved, and how the studies developed have contributed to the understanding of the neurobiology of depression. Secondly, the major problems regarding the clinical efficacy and acceptance of these drugs are discussed, and the introduction of the glutamatergic system as a target for antidepressant drugs is presented. Finally, we review how ketamine revealed itself as an exciting option towards obtaining pharmacological agents to treat depression, through the understanding of biological markers.DiscussionKetamine contributed to confirm that different targets of the glutamatergic system and neurotrophic pathways are strictly related to the neurobiology of depression. There are several antidepressant drugs based on ketamine's mechanism of action already in the pipeline, and glutamatergic-targeted antidepressants may be on the market in the near future.
Gene Transfer with Synthetic Cationic Amphiphiles: Prospects for Gene Therapy (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGene Transfer with Synthetic Cationic Amphiphiles: Prospects for Gene TherapyJean-Paul BehrCite this: Bioconjugate Chem. 1994, 5, 5, 382–389Publication Date (Print):September 1, 1994Publication History Published online1 May 2002Published inissue 1 September 1994https://pubs.acs.org/doi/10.1021/bc00029a002https://doi.org/10.1021/bc00029a002research-articleACS PublicationsRequest reuse permissionsArticle Views1038Altmetric-Citations314LEARN 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-Alertsclose Get e-Alerts
Identification of ROS1 rearrangement in gastric adenocarcinoma (2013)

In this study, an SLC34A2-ROS1 rearrangement was identified in GC, and the results provide a rationale for investigating the clinical efficacy of ROS1 inhibitors in this unique molecular subset of GC. Society.
1. The Lorentz Transformations (2018)

However, these transformations presuppose that time is a well-defined universal concept, that is to say, it’s the same time everywhere, and all observers can agree on what time it is. Once we accept the basic postulate of special relativity, however, that the laws of physics, including Maxwell’s equations, are the same in all inertial frames of reference, and consequently the speed of light has the same value in all inertial frames, then as we have seen, observers in different frames do not agree on whether clocks some distance apart are synchronized. Furthermore, as we have discussed, measurements of moving objects are compressed in the direction of motion by the Lorentz-Fitzgerald contraction effect. Obviously, the above equations are too naive! We must think more carefully about time and distance measurement, and construct new transformation equations consistent with special relativity.
Raman Analysis of Pharmaceuticals (2001)

Abstract Raman spectroscopy is an integral tool for the identification, qualitative characterization, and quantitative analysis of drugs at the drug substance and/or drug product level. Significant advances in Raman spectrometer hardware, software control and data processing techniques have lead to unique applications of the Raman spectroscopic technique within the pharmaceutical industry. This Chapter presents applications of Raman spectroscopy as applied to the analysis of pharmaceutical drug substances as well as drug products. At the drug substance level, applications include the chemical and physical characterization of the API, microanalysis, contaminant analysis, and surface characterization. An extensive discussion is also presented on quantitative pharmaceutical analysis by Raman spectroscopy at the drug substance and drug product level including univariate versus multivariate analysis and method validation.
Intrinsically Cell-Permeable Miniature Proteins Based on a Minimal Cationic PPII Motif (2007)

Cell-penetrating peptides (CPPs) provide promising tools for the cellular delivery of molecular cargos ranging in size from small molecules and peptides to proteins and quantum dots. CPPs are typically cationic and/or amphipathic sequences that are unstructured or alpha-helical. We expand the repertoire of cell-penetrating motifs by designing encodable CPPs possessing type-II polyproline (PPII) helical structure. These motifs surpass the uptake efficiency of existing CPPs and are not cytotoxic at concentrations 100 times greater than that necessary for delivery. By replacing the PPII helix of a miniature protein, the motif can endow intrinsic cell permeability without increasing molecular size.
Use of Classification Regression Tree in Predicting Oral Absorption in Humans (2004)

The purpose of this study is to explore the use of classification regression trees (CART) in predicting, in the dose-independent range, the fraction dose absorbed in humans. Since the results from clinical formulations in humans were used for training the model, a hypothetical state of drug molecules already dissolved in the intestinal fluid was adopted. Therefore, the molecular attributes affecting dissolution were not considered in the model. As a result, the model projects the highest achievable fraction dose absorbed, providing a reference point for manipulating the formulations or solid states to optimize oral clinical efficacy. A set of approximately 1260 structures and their human oral pharmacokinetic data, including bioavailability and/or absorption and/or radio-labeled studies, were used, with 899 compounds as the training set and 362 the test set. The numerical range of the fraction dose absorbed, 0 to 1, was divided into 6 classes with each class having a size of approximately 0.16. A set of 28 structural descriptors was used for modeling oral absorption without considering active transport. Then, a separate branch was created for modeling oral absorption involving active transport. The AAE of the training set was 0.12 and those of five test sets ranged from 0.17 to 0.2. In terms of classification, two test sets of unpublished, proprietary compounds showed 79% to 86% prediction when the predicted values fallen within +/- one class of real values were considered predicted. Overall, the computational errors from all the test sets of diverse structures were similar and reasonably acceptable. As compared to artificial membranes for ranking drug absorption potential, prediction by the CART model is considered fast and reasonably accurate for accelerating drug discovery. One can not only improve continuously the accuracy of CART computations by expanding the chemical space of the training set but also calculate the statistical errors associated with individual decision paths resulting from the training set to determine whether to accept individual computations of any test sets.
Flavonol Glycosides in Cranberries (1967)

SUMMARY The yellow flavonol glycosides were isolated from cranberries ( Vaccinium macrocarpon , Ait.) and identified by chromatographic, chemical, and spectral studies. The major pigment was quercetin‐3‐galactoside, followed by quercetin‐3‐hamnoside, quercetin‐3‐arabinoside, quercetin, myri‐cetin‐3.arabinoside, and myricetin‐3‐digalactoside.
Coactivator TIF1β Interacts with Transcription Factor C/EBPβ and Glucocorticoid Receptor To Induce α1-Acid Glycoprotein Gene Expression (1998)

The transcription of the alpha1-acid glycoprotein gene is induced by inflammatory cytokines and glucocorticoids. C/EBPbeta is a major transcription factor involved in the induction of the agp gene by some cytokines. In this report, we have identified a novel transcriptional intermediary factor, TIF1beta, which could enhance the transcription of the agp gene by the glucocorticoid receptor (GR) and C/EBPbeta. TIF1beta belongs to a subgroup of RING (really interesting new gene) finger proteins that contain a RING finger preceding two B box-type fingers and a putative coiled-coil domain (RBCC domain). Immunoprecipitation experiments showed that the interaction between GR and TIF1beta is ligand independent. The overexpression of the TIF1beta gene enhances GR-regulated expression in a ligand- and glucocorticoid-responsive element (GRE)-dependent manner. TIF1beta can also augment C/EBPbeta-mediated activity on wild-type and GRE-mutated agp genes, but this augmentation is diminished when all three C/EBPbeta-binding elements are mutated. Functional and biochemical characterizations indicated that the bZIP domain of C/EBPbeta and the RBCC domain, plant homeodomain finger, and bromodomain of TIF1beta are crucial for the interactions of these proteins. Taken together, these results suggest that TIF1beta serves as a converging mediator of signal transduction pathways of glucocorticoids and some inflammatory cytokines.
Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study (2014)

Patients with severe pulmonary arterial hypertension (PAH) in New York Heart Association (NYHA) functional class (FC) III/IV have a poor prognosis, despite survival benefits being demonstrated with intravenous epoprostenol. In this pilot study, the efficacy and safety of a triple combination therapy regimen in patients with severe PAH was investigated. Data from newly diagnosed NYHA FC III/IV PAH patients (n=19) initiated on upfront triple combination therapy (intravenous epoprostenol, bosentan and sildenafil) were collected retrospectively from a prospective registry. Significant improvements in 6-min walk distance and haemodynamics were observed after 4 months' triple combination therapy in 18 patients (p<0.01); 17 patients had improved to NYHA FC I or II. One patient was not included in the month 4 assessment (due to an emergency lung transplant in month 3). At the final evaluation (mean ± sd 32 ± 19 months), all 18 patients had sustained clinical and haemodynamic improvement. Overall survival estimates for the triple combination cohort were 100% at 1, 2 and 3 years. Expected survival calculated from the French equation was 75% (95% CI 68-82%), 60% (95% CI 50-70%) and 49% (95% CI 38-60%) at 1, 2 and 3 years, respectively. This pilot study provides preliminary evidence of the long-term benefits of upfront triple combination therapy in patients with severe PAH.
Reaction of squirrel monkeys to intratracheal inoculation with influenza/A/New Jersey/76 (swine) virus (1977)

To determine whether a model could be established for laboratory investigations, nine squirrel monkeys were inoculated intratracheally with 10(7) median egg-infectious doses of influenza virus type A/New Jersey/8/76 (HSW1N1) (swine influenza virus). They responded with clinically detectable illness including fever, leukopenia, decreased food consumption, increased respiratory rate, occasional coughing, labored breathing, nasal discharge, and lethargy. Convalescence was well advanced by the day 10. All monkeys excreted virus for 7 to 8 days. A scoring procedure (illness score) has been developed for use in studies of vaccine and chemotherapeutic efficacy.
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) (1998)

This study was performed on a family of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) subjects. Neuropathological alterations of small arteries consisting in thickening, reduplication and fragmentation of the internal elastic lamella, and granular periodic acid-Schiff-positive material deposited in the arterial media were demonstrated in 1 autopsy case by histochemistry and electron microscopy. This material reacted with a monoclonal antibody anti-elastin (aE), as demonstrated by immunohistochemistry and immunoelectron microscopy. Significant increases of aE-immunoreactivity and elastin mRNA expression were found in cultured skin fibroblasts from 5 family members genetically affected by CADASIL, but not genetically and clinically healthy members. These results suggest that alterations of the elastic apparatus are associated with CADASIL genotype and related to the clinical expression of the disease.
Effects of formoterol (BD 40A), a beta-adrenoceptor stimulant, on isolated guinea-pig lung parenchymal strips and antigen-induced SRS-A release in rats. (1984)

Formoterol was evaluated for its inhibitory effects on tissue tonus of the isolated guinea-pig lung parenchymal (peripheral airways) and tracheal (central airways) strips and on antigen-induced release of slow reactive substance of anaphylaxis (SRS-A) in the rat. Relaxant effects of formoterol in both parenchymal and tracheal strips were dose-dependent and were of similar potency. Formoterol was 44 and 100 times more potent than isoproterenol and salbutamol, respectively, in relaxing the parenchymal preparation. Propranolol, butoxamine and atenolol antagonized the relaxation of the parenchymal strips by formoterol in this order of decreasing potency; their slopes of regression line of the Schild plots were 0.809, 0.975 and 0.676, respectively. The inhibitory effect of intraperitoneally administered formoterol on (mouse) IgE-mediated SRS-A release in rat passive peritoneal anaphylaxis was 40 and 12200 times, respectively, more potent than those of salbutamol and disodium cromoglycate (DSCG). This action was antagonized by pretreatment with propranolol. In contrast to DSCG which dose-dependently inhibited histamine release, neither formoterol nor salbutamol was effective in inhibiting the release. The results indicate that formoterol potently relaxes the peripheral airways through stimulating the beta 2-adrenoceptors selectively as is the case in the central airways and that it significantly inhibits IgE-mediated SRS-A release through beta-adrenoceptor stimulation.
Juxtamembrane mutant V560GKit is more sensitive to Imatinib (STI571) compared with wild-type c-kit whereas the kinase domain mutant D816VKit is resistant. (2002)

Imatinib (Glivec; STI571) is an ATP-competitive kinase inhibitor of c-Abl, BCR/ABL, c-Kit, and platelet-derived growth factor receptor. Overexpression or constitutive activation of Kit by mutations have been associated with various malignancies. Mutations in the intracellular juxtamembrane region of Kit (e.g., V560G) are common in gastrointestinal stromal tumors and have been linked to poor prognosis. Mutations in the kinase domain of Kit (e.g., D816V) have been detected in mastocytosis, acute myeloid leukemia, and germ-cell tumors. To determine the sensitivity of Kit mutants to Imatinib in the same cellular background, wild-type Kit (WTKit), V560GKit and D816VKit were expressed in FDC-P1 cells. Growth of FDC(WTKit) was inhibited by Imatinib with GI50 (a concentration of drug at which 50% inhibition of growth occurs) of 0.1-0.2 microM but FDC(V560GKit) were more sensitive to Imatinib with a GI50 of 0.01-0.025 microM and FDC(D816VKit) were resistant to Imatinib with a GI50 greater than 5 microM. The naturally occurring isoforms of c-Kit did not differ in their sensitivity to Imatinib. Immunoprecipitation and Western blot analysis indicated that 1 microM Imatinib reduced phosphorylation of WTKit and completely blocked phosphorylation of V560GKit but did not affect D816VKit phosphorylation. In signaling studies, addition of stem cell factor (SCF) induced phosphorylation of ERK and Akt by WTKit, and ERK, Akt and STAT3 by V560GKit, which were all blocked by Imatinib. Imatinib also blocked the constitutive activation of Akt and STAT3 by V560GKit but had no affect on the constitutive activation of ERK, Akt, and STAT3 by D816VKit. Overall, these findings demonstrate the increased susceptibility of the Kit juxtamembrane mutant, V560G, and the resistance of the kinase domain mutant, D816V, to Imatinib compared with WTKit.
SH2/SH3 Adaptor Proteins Can Link Tyrosine Kinases to a Ste20-related Protein Kinase, HPK1 (1997)

Ste20-related protein kinases have been implicated as regulating a range of cellular responses, including stress-activated protein kinase pathways and the control of cytoskeletal architecture. An important issue involves the identities of the upstream signals and regulators that might control the biological functions of mammalian Ste20-related protein kinases. HPK1 is a protein-serine/threonine kinase that possesses a Ste20-like kinase domain, and in transfected cells activates a protein kinase pathway leading to the stress-activated protein kinase SAPK/JNK. Here we have investigated candidate upstream regulators that might interact with HPK1. HPK1 possesses an N-terminal catalytic domain and an extended C-terminal tail with four proline-rich motifs. The SH3 domains of Grb2 bound in vitro to specific proline-rich motifs in the HPK1 tail and functioned synergistically to direct the stable binding of Grb2 to HPK1 in transfected Cos1 cells. Epidermal growth factor (EGF) stimulation did not affect the binding of Grb2 to HPK1 but induced recruitment of the Grb2.HPK1 complex to the autophosphorylated EGF receptor and to the Shc docking protein. Several activated receptor and cytoplasmic tyrosine kinases, including the EGF receptor, stimulated the tyrosine phosphorylation of the HPK1 serine/threonine kinase. These results suggest that HPK1, a mammalian Ste20-related protein-serine/threonine kinase, can potentially associate with protein-tyrosine kinases through interactions mediated by SH2/SH3 adaptors such as Grb2. Such interaction may provide a possible mechanism for cross-talk between distinct biochemical pathways following the activation of tyrosine kinases.
Luminescent Ruthenium(II) Bipyridyl−Phosphonic Acid Complexes:  pH Dependent Photophysical Behavior and Quenching with Divalent Metal Ions (1999)

The synthesis, redox behavior, and photophysical properties of a series of Ru(II) bipyridyl complexes having diimine ligands with phosphonate and phosphonic acid substituents are presented. The phosphonate-containing ligands examined include diethyl 4-(2,2'-bipyrid-4-yl)benzylphosphonate (bpbzp), diethyl 4-(2,2'-bipyrid-4-yl)-phenylphosphonate (bppp), and 4,4'-(diethyl phosphonato)-2,2'-bipyridine (bpdp), and the [(bpy)2Ru(L)](PF6)2 complexes of both the diethyl phosphonate and the phosphonic acid were prepared. The Ru(III/II) potentials are more positive for the phosphonate complexes than for the phosphonic acids, and the first reduction is localized on the phosphonate-containing ligand for the bppp and bpdp complexes. The first reduction of the phosphonic acid complexes is at more negative potentials and cannot be distinguished from bpy reduction. For the bppp and bpdp complexes luminescence arises from a Ru(d pi)-->bpy-phosphonate (pi*) MLCT state; the phosphonic acid complexes luminescence at higher energies from a MLCT state not clearly isolated on one ligand. Iron(III) and copper(II) complex with and very efficiently quench the luminescence of all the phosphonic acid complexes in nonaqueous solvents. The quenching mechanism is discussed on the basis of luminescence decay and picosecond transient absorption measurements.
Decline in NRF2-regulated Antioxidants in Chronic Obstructive Pulmonary Disease Lungs Due to Loss of Its Positive Regulator, DJ-1 (2008)

NRF2-dependent antioxidants and DJ-1 expression was negatively associated with severity of COPD. Therapy directed toward enhancing NRF2-regulated antioxidants may be a novel strategy for attenuating the effects of oxidative stress in the pathogenesis of COPD.
Therapy development for ALS: Lessons learned and path forward (2008)

Several therapies have shown promise in preclinical models of motor neuron disease. Several of these treatment approaches, however, failed in human studies. In moving forward with new promising therapies, it is important to first identify whether the past trials were unsuccessful due to wrong therapy and biological target or because of flaws in trial design and conduct. We review treatment development in ALS and discuss the strengths and limitations of past clinical trials. Better biomarkers of disease and markers of biological activity of the therapies under development are urgently needed. Obtaining information regarding dosage, pharmacokinetics, short-term safety and biological activity in well designed phase I and II studies is critical to the design of phase III trials that will yield meaningful results.