gebhart/patrepeval huggingface dataset:
In vitro activities of BAY Y3118, ciprofloxacin, ofloxacin, and fleroxacin against gram-positive and gram-negative pathogens from respiratory tract and soft tissue infections (1993)

BAY Y3118 was highly active against Moraxella catarrhalis, Haemophilus influenzae, Legionella pneumophila, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus (except quinolone-resistant, methicillin-resistant S. aureus), Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus pneumoniae (MIC for 90% of strains tested [MIC90], 0.063 micrograms/ml). For Enterococcus faecalis and Corynebacterium jeikeium, MIC90s were 4 and 2 micrograms/ml, respectively. BAY Y3118 was as active as ciprofloxacin against Pseudomonas aeruginosa (MIC90, 0.5 micrograms/ml) and had potent activity against Bacteroides fragilis (MIC90, 0.5 micrograms/ml).
Structure−Activity Relationship Study of Tricyclic Necroptosis Inhibitors (2007)

Necroptosis is a regulated caspase-independent cell death mechanism that can be induced in multiple cell types and is characterized by morphological features resembling necrosis. Here we describe a series of tricyclic heterocycles (i.e., 3-phenyl-3,3a,4,5-tetrahydro-2H-benz[g]indazoles, 3-phenyl-2,3,3a,4-tetrahydro[1]benzopyrano[4,3-c]pyrazoles, 3-phenyl-2,3,3a,4-tetrahydro[1]benzothiopyrano[4,3-c]pyrazoles, and 5,5-dioxo-3-phenyl-2,3,3a,4-tetrahydro[1]benzothiopyrano[4,3-c]pyrazoles], collectively termed Nec-3, that can potently inhibit necroptosis. For example, compounds 8, 22, 41, 53, and 55 inhibit necroptosis in an FADD-deficient variant of human Jurkat T cells treated for 24 h with TNF-alpha with EC50 values in the range 0.15-0.29 microM. Distinct from the previously described series of hydantoin-containing indole derivatives (Nec-1), the Nec-3 series exhibits specificity in inhibiting TNF-alpha-induced necroptosis. A structure-activity relationship (SAR) study revealed that the (3R,3aR)-rel-diastereomers were more active than the (3R,3aS)-rel-diastereomers for all four ring systems. Introduction of fluorine or methoxy to the 8-position of the tricyclic ring and a methoxy to the 4-position of the pendent phenyl ring increased activity. Amides at the 2-position of the tricyclic ring were best. The Nec-3 series provides new tools for elucidating caspase-independent cell death pathways and potentially lead compounds for therapeutic development.
Constitutive OX40/OX40 Ligand Interaction Induces Autoimmune-Like Diseases (2002)

The interaction between OX40 and OX40 ligand (OX40L) is suggested to provide T cells with an effective costimulatory signals during T cell-APC interaction. To examine the in vivo effect of constitutive OX40/OX40L interaction during immune regulation, we report the establishment of OX40L-transgenic (OX40L-Tg) mice that constitutively express OX40L on T cells. Markedly elevated numbers of effector memory CD4(+) T cells, but not CD8(+) T cells, were observed in the secondary lymphoid organs of OX40L-Tg mice. Upon immunization with keyhole limpet hemocyanin in the absence of adjuvant, profound T cell proliferative responses and cytokine productions were seen in the OX40L-Tg mice as compared with wild-type mice. Furthermore, in OX40L-Tg mice administrated with superantigen, this constitutive OX40/OX40L interaction on CD4(+) T cells completely prevented normal in vivo clonal T cell deletion. Interestingly, OX40L-Tg mice on the C57BL/6 background spontaneously developed interstitial pneumonia and inflammatory bowel disease that was accompanied with a significant production of anti-DNA Ab in the sera. Surprisingly, these diseases were not evident on the OX40L-Tg mice on the BALB/c strain. However, such inflammatory diseases were successfully reproducible in recombination-activating gene (RAG)2-deficient mice upon transfer of OX40L-Tg CD4(+) T cells. Blockade of OX40/OX40L interaction in the recipient RAG2-deficient mice completely prevented disease development. The present results orchestrated in this study indicate that OX40/OX40L interaction may be a vital link in our understanding of T cell-mediated organ-specific autoimmunity.
Automatic Generation of Emotionally-Targeted Soundtracks. (2011)

Music can be used both to direct and enhance the impact a story can have on its listeners. This work makes use of two creative systems to provide emotionally-targeted musical accompaniment for stories. One system assigns emotional labels to text, and the other generates original musical compositions with targeted emotional content. We use these two programs to generate music to accompany audio readings of fairy tales. Results show that music with targeted emotional content makes the stories significantly more enjoyable to listen to and increases listener perception of emotion in the text.
The Human IgG subclasses : molecular analysis of structure, function, and regulation (1990)

Section I: Structure. Introduction, R S H Pumphrey. Molecular structure of human IgG subclasses, R Jefferis. Fragmentation and conformational changes of IgG subclasses, T E Michaelsen. Molecular genetics of immunoglobulin allotype expression, M-P Lefranc & G Lefranc Production and epitope location of monoclonal antibodies to the human IgG subclasses, R G Hamilton. Structure/function relationships of IgG subclasses, R Jefferis. Section II: Function. Membrane Fc receptors for IgG subclasses, J D Pound & M R Walke . The ability of IgG subclasses to cause the elimination of targets in vivo and to mediate their destruction by phagocytosis/cytolysis in vitro , E Wiener. Selective IgG subclass expression: biologic, clinical and functional significance, M G Scott, D E Briles & M H Nahm. Affinity of IgG subclass antibodies, M E Devey. Construction, expression and function of chimaeric antibodies, M Bruggemann. Section III: Regulation. Molecular genetics of immunoglobulin variable regions, M J Sims & M J Tauss g. The cellular and molecular biology of cytokine-directed murine IgG isotype production, C M Snapper. Regulation of immunoglobulin isotypes by self structures, N R StC Sinclair. Subclass restrictions of IgG antibody responses, L Hammarstrom & C I E Smi h.
β-Amyloid Monomers Are Neuroprotective (2009)

The 42-aa-long beta-amyloid protein--Abeta(1-42)--is thought to play a central role in the pathogenesis of Alzheimer's disease (AD) (Walsh and Selkoe, 2007). Data from AD brain (Shankar et al., 2008), transgenic APP (amyloid precursor protein)-overexpressing mice (Lesné et al., 2006), and neuronal cultures treated with synthetic Abeta peptides (Lambert et al., 1998) indicate that self-association of Abeta(1-42) monomers into soluble oligomers is required for neurotoxicity. The function of monomeric Abeta(1-42) is unknown. The evidence that Abeta(1-42) is present in the brain and CSF of normal individuals suggests that the peptide is physiologically active (Shoji, 2002). Here we show that synthetic Abeta(1-42) monomers support the survival of developing neurons under conditions of trophic deprivation and protect mature neurons against excitotoxic death, a process that contributes to the overall neurodegeneration associated with AD. The neuroprotective action of Abeta(1-42) monomers was mediated by the activation of the PI-3-K (phosphatidylinositol-3-kinase) pathway, and involved the stimulation of IGF-1 (insulin-like growth factor-1) receptors and/or other receptors of the insulin superfamily. Interestingly, monomers of Abeta(1-42) carrying the Arctic mutation (E22G) associated with familiar AD (Nilsberth et al., 2001) were not neuroprotective. We suggest that pathological aggregation of Abeta(1-42) may also cause neurodegeneration by depriving neurons of the protective activity of Abeta(1-42) monomers. This "loss-of-function" hypothesis of neuronal death should be taken into consideration when designing therapies aimed at reducing Abeta burden.
Oxcarbazepine in a monotherapy trial for partial seizures--Placebo-controlled studies in neurology: Where do they stop? (1999)

To the Editor:

The editorial by Drs. Chadwick and Privitera1 that accompanied our report of a placebo-control monotherapy trial of oxcarbazepine for partial seizures2 carries forward the recent spirited discussion in the literature about the design and importance of monotherapy studies in epilepsy.3-5 However, we feel compelled to respond to their assertions concerning the clinical value and ethics of our study.

Was our study clinically valuable? Absolutely. Because of its placebo-controlled design, our study convincingly established the antiseizure activity of oxcarbazepine. This demonstration has significant value because proof of efficacy is justifiably essential for a drug to be licensed in the United States. In addition, our study showed that oxcarbazepine can be safely titrated over one day and that its antiseizure effects begin rapidly. This finding is meaningful to clinicians because of the paucity of other controlled studies that show antiepileptic drug (AED) efficacy in an acute setting.

Was our study ethical? The principal investigators, co-investigators, and sub-investigators, all of whom were associated with leading academic medical centers, as well as their institutional review boards and their clinical research center scientific advisory boards (where applicable) would not have otherwise performed or approved this study. However, Chadwick and Privitera argue that our study compromised two of Beauchamp and Childress’ principles of medical ethics—beneficence and nonmaleficence6—and their balance, or equipoise.7 We strongly disagree. Equipoise existed in our study because beneficence for oxcarbazepine had not been previously established, in our opinion. Yes, oxcarbazepine is indeed widely licensed for the treatment of epilepsy in Europe and is structurally similar to carbamazepine. But in this era of evidence-based medicine, how convincing is the previously published data that oxcarbazepine is effective?

As clinicians, we agree that comparative monotherapy trials, such as the widely influential Veterans Administration Cooperative Study, …
Lessons learned: The conditional importance of high positive end-expiratory pressure in acute respiratory distress syndrome* (2006)

University of Minnesota, Minneapolis/St. Paul, MN The author has no financial interests to disclose.
Definitions and guidelines for assessment of wounds and evaluation of healing (1994)

Chronic wounds represent a worldwide problem. For laboratory and clinical research to adequately address this problem, a common language needs to exist. This language should include a system of wound classification, a lexicon of wound descriptors, and a description of the processes that are likely to affect wound healing and would healing end points. The report that follows defines wound, acute wound, chronic wound, healing and forms of healing, wound assessment, wound extent, wound burden, and wound severity. The utility of these definitions is demonstrated as they relate to the healing of a skin wound, but these definitions are broadly applicable to all wounds.
Abuse of Smoking Methamphetamine Mixed with Tobacco: I. Inhalation Efficiency and Pyrolysis Products of Methamphetamine (1987)

Experiments of smoking methamphetamine in tobacco have been investigated. Inhalation efficiencies of methamphetamine into tar were 6 to 17% according to the additive amounts, suction volume, and intervals of smoking. Major pyrolysis products of methamphetamine in tar were identified as methamphetamine, amphetamine, phenylacetone, dimethylamphetamine, N-formyl-, N-acetyl-, N-propionyl-, and N-cyanomethyl-methamphetamine by the spectral analysis of infrared spectra (IR), mass spectra (MS), and proton magnetic resonance spectra (PMR), and comparison with the samples synthesized from authentic samples by one step. The largest pyrolysis product was N-cyanomethylmethamphetamine which is a new compound and easily metabolized to methamphetamine in the body. Methamphetamine itself transferred into tar was not so large, but the total active compounds in tar which would be metabolized to methamphetamine in the body were considerably larger.
A combinatorially convenient version of synthesis of 5-substituted oxazole-4-carboxylic acid ethyl esters (2006)

Reaction of ethyl isocyanoacetic acid with sodium hydride in anhydrous benzene, followed by treatment with carboxylic acid chlorides or N-(acyloxy)pyrrolidine-2,5-diones, gives 5-substituted oxazole-4-carboxylic acid esters. The procedure is applicable to derivatives of various carboxylic acids, including saturated aliphatic, α,β-unsaturated, alicyclic, aromatic, heterocyclic, and N-Boc-protected amino acids.
Production of Polyclonal Antisera (1999)

Polyclonal antibody preparations contain multiple antibody molecules recognizing different epitopes on an antigen molecule. Good quality polyclonal antisera are useful for a number of applications-e.g., immunoprecipitation, immunoblotting, and ELISAs-where the binding of more than one antibody molecule per antigen molecule improves the sensitivity of the assay. It is possible to produce polyclonal antibodies in a variety of species, and this make it possible to detect multiple immunoreactions. The protocols in this unit describe the production of polyclonal antisera specific for protein antigens in rabbits, rats, mice, and hamsters using complete Freund's adjuvant (CFA) or other adjuvants. In addition, the unit presents a method for preparing serum from blood. Polyclonal antipeptide antisera can be produced by substituting carrier-conjugated peptides for the purified protein antigens.
Association between Tumor Necrosis Factor-α and Disease Progression in Patients with Multiple Sclerosis (1991)

Background. Cachectin, or tumor necrosis factor-α (TNF-α), is a principal mediator of the inflammatory response and may be important in the pathogenesis and progression of multiple sclerosis, an inflammatory disease of the central nervous system. Methods. In a 24-month prospective study, we used a sensitive enzyme-linked immunosorbent assay to determine levels of TNF-α in cerebrospinal fluid and serum in 32 patients with chronic progressive multiple sclerosis and in 20 with stable multiple sclerosis and 85 with other neurologic diseases. An attempt was made to relate TNF-α levels with the degree of disability of the patients with multiple sclerosis and with their neurologic deterioration during the 24 months of observation. Results. High levels of TNF-α were found in the cerebrospinal fluid of 53 percent of the patients with chronic progressive multiple sclerosis and in none of those with stable multiple sclerosis (P<0.001). TNF-α was detected in the cerebrospinal fluid of 7 percent of the controls (P<0.01) with other neurologic disease. In patients with chronic progressive multiple sclerosis, mean TNF-α levels were significantly higher in the cerebrospinal fluid than in corresponding serum samples (52.41 vs. 11.88 U per milliliter; range, 2 to 178 vs. 2 to 39; P<0.001). In these patients, cerebrospinal fluid levels of TNF-α correlated with the degree of disability (r = 0.834, P<0.001) and the rate of neurologic deterioration (r = 0.741, P<0.001) before the start of the study. Cerebrospinal fluid levels also correlated with the increase in neurologic disability after 24 months of observation (r = 0.873, P<0.001). Conclusions. These data provide evidence of intrathecal synthesis of TNF-α in multiple sclerosis and suggest that the level of TNF-α in cerebrospinal fluid correlates with the severity and progression of the disease. Our results suggest that TNF-α may reflect histologic disease activity in multiple sclerosis and could be used to monitor outcomes or responses to therapy. (N Engl J Med 1991; 325:467–72.). © 1991, Massachusetts Medical Society. All rights reserved.
Atomic-layer cleaving with Si/sub x/Ge/sub y/ strain layers for fabrication of Si and Ge-rich SOI device layers (2002)

Methods to fabricate multi-layer SOI structures have evolved from epitaxial growth of Si on sapphire and grind-back of bonded layers (in the 1970s) to direct implantation of oxygen (SIMOX) and etching of bonded wafers (from the 1980s) to bonded processes that exploit fracture of porous layers by thermal (ion/Smart-cut) or mechanical (Eltran) stress (in the 1990s). The recent development of controlled cleaving techniques using, engineered SiGe strain layers (NanoCleave/sup TM/) in conjunction with advances in layer bonding and thickness modification results in marked improvements in film thickness control. film and surface quality and production efficiency over earlier methods.
A Most Unusual Zeolite Templating: Cage to Cage Connection of One Guest Molecule (2010)

An unusual case of a diquaternary ammonium dication, with large bulky end groups built from the tropane moiety and connected by a C4 methylene chain, is found to reside in zeolite SSZ-35 (STF). The structure of the guest/host product is such that the tropane bicylic entities reside in the shallow cavities of the cages of the STF structure and the C4 methylene chain runs through the 10-ring (∼5.5 Å) window that connects the cages. This is a most unusual (and energy-intensive) templating of a zeolite structure with the guest molecule spanning two unit cells. The unusual result was found by single crystal studies with the addition of the use of the SQUEEZE program to show a consistent fit for the guest molecule following from measured electron densities in the crystal structure work. These analyses were followed with MAS NMR studies to confirm the integrity of the diquaternary guest molecule in the host sieve. A few comparative diquaternary guest molecules in MFI zeolite are also studied.
A Cluster of Structural and Regulatory Genes for Light‐Induced Carotenogenesis in Myxococcus xanthus (1995)

In the bacterium Myxococcus xanthus, several genes for carotenoid synthesis lie together at the carA-carB chromosomal locus and are co-ordinately activated by blue light. A 12-kb DNA stretch from wild-type M. xanthus has been sequenced that includes the entire carA-carB gene cluster. According to sequence analysis, the cluster contains 11 different genes. Intergenic distances are very short or nil (implying translational coupling), giving further support to previous evidence indicating that most (or all) of the genes in the cluster form a single operon. At the promoter region, a potential -35 site for the binding of sigma factors is found. However, the -10 region shows little similarity with analogous sites in other bacterial promoters. Five (possibly six) genes in the carA-carB operon code for enzymes acting on early or late steps of the pathway for carotenoid synthesis. Other genes in the operon show no overall similarity with previously known genes. However, peptide stretches in the predicted products of two genes exhibit strong similarity with the DNA binding domain of the MerR family of transcriptional regulators. At least one of the predicted DNA-binding domains is altered in a mutant strain affected in light-regulation of the car genes.
Testing intravitreal toxicity of rapamycin in rabbit eyes (2009)

Although ERG changes were identified at dosages between 50-1000 microg, the histology of all groups up to 1000 microg did not show any discernable abnormalities.
Effect of Xyfoglucan (Tamarind Seed Polysaccharide) on Conjunctival Cell Adhesion to Laminin and on Corneal Epithelium Wound Healing (2000)

The ability of the polysaccharide to promote corneal wound healing might depend on its influence on the integrin recognition system.
High-Speed VLSI Multiplication Algorithm with a Redundant Binary Addition Tree (1985)

A high-speed VLSI multiplication algorithm internally using redundant binary representation is proposed. In n bit binary integer multiplication, n partial products are first generated and then added up pairwise by means of a binary tree of redundant binary adders. Since parallel addition of two n-digit redundant binary numbers can be performed in a constant time independent of n without carry propagation, n bit multiplication can be performed in a time proportional to log2 n. The computation time is almost the same as that by a multiplier with a Wallace tree, in which three partial products will be converted into two, in contrast to our two-to-one conversion, and is much shorter than that by an array multiplier for longer operands. The number of computation elements of an n bit multiplier based on the algorithm is proportional to n2. It is almost the same as those of conventional ones. Furthermore, since the multiplier has a regular cellular array structure similar to an array multiplier, it is suitable for VLSI implementation. Thus, the multiplier is excellent in both computation speed and regularity in layout. It can be implemented on a VLSI chip with an area proportional to n2 log2 n. The algorithm can be directly applied to both unsigned and 2's complement binary integer multiplication.
Gas Phase Synthesis, Structure, and Dissociation of Boron Triazide (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGas Phase Synthesis, Structure, and Dissociation of Boron TriazideR. L. Mulinax, G. S. Okin, and R. D. CoombeCite this: J. Phys. Chem. 1995, 99, 17, 6294–6300Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://doi.org/10.1021/j100017a007RIGHTS & PERMISSIONSArticle Views175Altmetric-Citations28LEARN 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 InReddit PDF (805 KB) Get e-Alerts
Reserpine labels the catecholamine transporter in synaptic vesicles from bovine caudate nucleus (1983)

Tritiated reserpine binds to synaptic vesicles from bovine caudate with high affinity (Kappd = 1.25 nM, Bmax = 3.3 pmol/mg protein). This interaction is both ATP-dependent and sensitive to the protonophores CCCP and nigericin, suggesting that a proton electrochemical gradient is required for binding. Dopamine, epinephrine, norepinephrine and serotonin all inhibit reserpine binding at concentrations similar to those required for inhibition of dopamine uptake. Treatment with saponin to release vesicle contents results in complete loss of accumulated dopamine but retention of bound reserpine. These results indicate that reserpine binds to the catecholamine transport system of synaptic vesicles with high affinity and specificity.
Some Facts That You Might Be Unaware of About the P-Value (2017)

Recently, some articles on the P-value published in biomedical journals caught my eye. These articles included the words 'misuse,' 'misconception,' or 'misinterpretation' of the P-value in their titles or abstracts. Nuzzo [1] stated that P-values, the 'gold standard' of statistical validity, are not as reliable as many scientists assume and added that 'the P-value was never meant to be used the way it's used today.' Greenland et al. [2] provided an explanatory list of 18 misinterpretations of P-values and guidelines for improving statistical interpretation. Other interesting articles include a paper by Chavalarias et al. [3] and the accompanying editorial by Kyriacou [4] published in the Journal of the American Medical Association, and a review paper by van Rijn et al. [5]. Not only in biomedical communities, but also in a major statistical society, a statement on P-values has been issued in order to sound the alarm about the misuse of P-values [6].