gebhart/patrepeval huggingface dataset:
Market feedback replaces regulation: Adaptation in the electric power industry (1998)

The electric utilities are not generally thought of as innovators, but with the impending deregulation of the market for power, this could change. The utility industry is faced with the need to become adaptive in real time, to respond to the rapidly changing demand for power on a given day in an environment in which marginal cost varies in hard-to-predict ways and profits are not guaranteed. Several firms in the industry are turning to complexity-based approaches to simulate plant operations, estimate marginal costs in real time, and develop strategies for buying and selling power. This article describes three problems and approaches. It is surprising that utilities should be among the pioneers in applying complexity to business; we might speculate that it is the lack of other, traditional decision-making processes for dealing with competitive markets that is making room for complexity to take root. Due to the protected environment of regulation, the industry has not previously needed the entrenched tools of marketing and profits maximization developed for competitive decision-making.
Recent advances in the development of multifactorial therapies for the treatment of traumatic brain injury (2004)

Traumatic brain injury (TBI) is one of the leading causes of death and disability in the industrialised world and remains a major health problem with serious socioeconomic consequences. So far, despite encouraging preclinical results, almost all neuroprotection trials have failed to show any significant efficacy in the treatment of clinical TBI. This may be due, in part, to the fact that most of the therapies investigated have targeted an individual injury factor. It is now recognised that TBI is a very heterogeneous type of injury that varies widely in its aetiology, clinical presentation, severity and pathophysiology. The pathophysiological sequelae of TBI are mediated by an interaction of acute and delayed molecular, biochemical and physiological events that are both complex and multifaceted. Accordingly, a successful TBI treatment may have to simultaneously attenuate many injury factors. Recent efforts in experimental TBI have, therefore, focused on the development of neuropharmacotherapies that target multiple injury factors and thus improve the likelihood of a successful outcome. This review will focus on three such novel compounds that are currently being assessed in clinical trials; progesterone, dexanabinol and dexamethasone, and provide an update on the progress of both magnesium and cyclosporin A.
Enzyme‐Linked Immunosorbent Assays (ELISA) (1991)

This unit describes six different ELISA systems for the detection of specific antibodies, soluble antigens, or cell-surface antigens. In all six systems, soluble reactants are removed from solution after specifically binding to solid-phase reactants. In the first four protocols, solid-phase reactants are prepared by adsorbing an antigen or antibody onto plastic microtiter plates; in the next two protocols, the solid-phase reactants are cell-associated molecules. In all protocols, the solid-phase reagents are incubated with secondary or tertiary reactants covalently coupled to an enzyme. Unbound conjugates are washed out and a chromogenic or fluorogenic substrate is added. As the substrate is hydrolyzed by the bound enzyme conjugate, a colored or fluorescent product is generated. Finally, the product is detected visually or with a microtiter plate reader. The amount of product generated is proportional to the amount of analysate in the test mixture. Support protocols are provided for optimizing the different ELISAs and preparing lysates for use as test antigen from bacterial cultures containing expressed protein.
Clinical Effects of Raloxifene Hydrochloride in Women (1999)

Raloxifene has been shown to have beneficial effects in selected organs in postmenopausal women. Although estrogen remains the drug of choice for hormonal therapy in most postmenopausal women, raloxifene may be an alternative in certain groups of women at risk for osteoporosis.
Function of Cytokines within the TGF-&#946; Superfamily as Determined from Transgenic and Gene Knockout Studies in Mice (2002)

Several major conceptual problems regarding specific in vivo functions of the TGF-beta family members remain the key focus of many researchers studying the biology of these secreted signaling molecules. More than 45 members of this family of growth factors have been identified and partially characterized for their molecular roles in numerous processes such as cell proliferation and differentiation, embryonic development, carcinogenesis, immune dysfunction, inflammation and wound healing. The high degree of similarity that exists at the structural level among the isoforms of these growth factors is accompanied by a significant overlap in function, as defined by many in vitro model systems and in vivo systems involving administration of exogenous ligand or of ligand-specific blocking antibodies. The ability to discern the critical functions of these molecules based on patterns of expression has also often been quite difficult. The evolution of more sophisticated functional genomics approaches has been recently instrumental in generating unique perspectives into the mechanisms governing the activity of the members of the TGF-beta family. The studies outlined in this review are significant in that they not only support working hypotheses regarding the activities of TGF-beta generated through extensive in vitro studies but also raise new questions regarding the role of each isoform in numerous processes. With the rapid advances in these approaches to probe activity in a more cell and time-dependent fashion, we will gain valuable insights for designing approaches for targeting the complex cellular pathways mediating their responses and will also help us develop novel therapies to treat disease processes.
CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection (1994)

In this study, we have examined the relative contributions of CD4+ and CD8+ T cells in controlling an acute or chronic lymphocytic choriomeningitis virus (LCMV) infection. To study acute infection, we used the LCMV Armstrong strain, which is cleared by adult mice in 8 to 10 days, and to analyze chronic infection, we used a panel of lymphocyte-tropic and macrophage-tropic variants of LCMV that persist in adult mice for several months. We show that CD4+ T cells are not necessary for resolving an acute LCMV infection. CD4+ T-cell-depleted mice were capable of generating an LCMV-specific CD8+ cytotoxic T-lymphocyte (CTL) response and eliminated virus with kinetics similar to those for control mice. The CD8+ CTL response was critical for resolving this infection, since beta 2-microglobulin knockout (CD8-deficient) mice were unable to control the LCMV Armstrong infection and became persistently infected. In striking contrast to the acute infection, even a transient depletion of CD4+ T cells profoundly affected the outcome of infection with the macrophage- and lymphocyte-tropic LCMV variants. Adult mice given a single injection of anti-CD4 monoclonal antibody (GK1.5) at the time of virus challenge became lifelong carriers with high levels of virus in most tissues. Unmanipulated adult mice infected with the different LCMV variants contained virus for prolonged periods (> 3 months) but eventually eliminated infection from most tissues, and all of these mice had LCMV-specific CD8+ CTL responses. Although the level of CTL activity was quite low, it was consistently present in all of the chronically infected mice that eventually resolved the infection. These results clearly show that even in the presence of an overwhelming viral infection of the immune system, CD8+ CTL can remain active for long periods and eventually resolve and/or keep the virus infection in check. In contrast, LCMV-specific CTL responses were completely lost in chronically infected CD4-depleted mice. Taken together, these results show that CD4+ T cells are dispensable for short-term acute infection in which CD8+ CTL activity does not need to be sustained for more than 2 weeks. However, under conditions of chronic infection, in which CD8+ CTLs take several months or longer to clear the infection, CD4+ T-cell function is critical. Thus, CD4+ T cells play an important role in sustaining virus-specific CD8+ CTL during chronic LCMV infection. These findings have implications for chronic viral infections in general and may provide a possible explanation for the loss of human immunodeficiency virus-specific CD8+ CTL activity that is seen during the late stages of AIDS, when CD4+ T cells become limiting.
The Physical State of Human Papillomavirus Type 16 DNA in Benign and Malignant Genital Tumours (1985)

SUMMARY Cloned DNA from human papillomavirus (HPV) type 16 was subjected to restriction enzyme analysis. A genome size of 7.8 ± 0.1 kb was determined and restriction maps were prepared. Fragments of HPV 16 DNA were nick-translated and hybridized with fragments of HPV 6b DNA. The two genomes appeared to be colinear. The physical state of HPV 16 DNA in genital tumours was analysed. In each of six benign tumours the viral DNA was detected exclusively as 8 kb circles. In four malignant tumours the viral DNA appeared to be integrated within the host genome but one cervical carcinoma and one case of Bowen’s disease also contained oligomeric episomal molecules of viral DNA. One cervical carcinoma (WV 2965), containing only integrated viral DNA, was examined in detail. HPV 16 DNA was integrated as head-to-tail tandem repeats at more than one site. Three virus/cell junction fragments from this tumour were cloned. Two contained lengths of repetitive cellular DNA and one a length of apparently single copy cellular DNA.
A cDNA clone coding for a novel allergen, Cla h III, of Cladosporium herbarum identified as a ribosomal P2 protein. (1995)

Mold allergens represent a major cause of atopic disorders. Progress in the molecular characterization of allergens has been hampered by batch-to-batch variation and poor yields in mold extracts. In the present study, we established a cDNA library in lambda ZAP II by using mRNA isolated from a major allergen-producing mold, Cladosporium herbarum. From this library, a novel allergen has been cloned and sequenced. The clone encodes a full length protein of 111 amino acids with a molecular mass of 11.1 kDa and pI of 3.94. By using sequence homology analysis, the allergen was found to belong to the ribosomal P2 protein family. Approximately 60% peptide sequence homology was found between the cloned protein and other known fungal ribosomal P2 proteins. In addition to conserved C-terminal sequences and serine blocks for phosphorylation in all eukaryotic ribosomal P2 proteins, this protein also contains a potential N-glycosylation site at position 15-17. Northern blots demonstrated that mRNA molecules of this gene are present even at late stages of culture. The gene was expressed in Escherichia coli by using the pMAL-2c system, and murine antisera against the recombinant allergen (rCh2.1) were generated. The antisera revealed that the native allergen corresponding to rCh2.1 was present in extracts prepared by grinding mycelia under liquid nitrogen in the presence of protease inhibitors, but absent in extracts prepared by conventional methods. This result indicates the usefulness of recombinant allergens in characterization and standardization of mold allergenic extracts.
Increased amyloidogenic secretion in cerebellar granule cells undergoing apoptosis (1998)

Some clues suggest that neuronal damage induces a secondary change of amyloid beta protein (Abeta) metabolism. We investigated this possibility by analyzing the secretion of Abeta and processing of its precursor protein (amyloid precursor protein, APP) in an in vitro model of neuronal apoptosis. Primary cultures of rat cerebellar granule neurons were metabolically labeled with [35S]methionine. Apoptosis was induced by shifting extracellular KCl concentration from 25 mM to 5 mM for 6 h. Control and apoptotic neurons were then subjected to depolarization-stimulated secretion. Constitutive and stimulated secretion media and cell lysates were immunoprecipitated with antibodies recognizing regions of Abeta, full-length APP, alpha- and beta-APP secreted forms. Immunoprecipitated proteins were separated by SDS/PAGE and quantitated with a PhosphorImager densitometer. Although intracellular full-length APP was not significantly changed after apoptosis, the monomeric and oligomeric forms of 4-kDa Abeta were 3-fold higher in depolarization-stimulated secretion compared with control neurons. Such increments were paralleled by a corresponding increase of the beta-APPs/alpha-APPs ratio in apoptotic secretion. Immunofluorescence studies performed with an antibody recognizing an epitope located in the Abeta sequence showed that the Abeta signal observed in the cytoplasm and in the Golgi apparatus of control neurons is uniformly redistributed in the condensed cytoplasm of apoptotic cells. These studies indicate that neuronal apoptosis is associated with a significant increase of metabolic products derived from beta-secretase cleavage and suggest that an overproduction of Abeta may be the consequence of neuronal damage from various causes.
A Three-Dimensional Shaded Display Method for Voxel-Based Representation (1985)

In this paper, methods for displaying solid objects represented by a three-dimensional array of voxels are described. The Linear Interpolating Projection Method is proposed as a method by which such objects can be projected onto the screen in perspective. In order to shade the projected images, the Depth only Shading Method is proposed. These methods are so simple that three-dimensional perspective images with shading can be produced rapidly. This paper also describes an architecture based on these methods for generating animation interactively.
A novel tandem germline RET mutations on the same allele in a patient with MEN 2B (2012)

Four studies tested whether uncertainty about the self-concept can motivate people, particularly individualists who define themselves in terms of their personal traits and characteristics, to perceive their material possessions as extensions of themselves (i.e., as self-expressive). In Study 1, European American participants rated their favorite pair of blue jeans as more self-expressive after being induced to feel self-uncertain, whereas Asian American participants did not. In Study 2, participants who scored high on a measure of individualism rated their cars as more self-expressive following a self-uncertainty manipulation. In Study 3, individualists (but not collectivists) rated their favorite possessions as more self-expressive after being subject to self-uncertainty; a manipulation of self-irrelevant uncertainty did not produce these results. In Study 4, thinking about a self-expressive (relative to utilitarian) possession bolstered self-certainty among individualists, but not collectivists. Implications for research on culture, the self-concept, and possessions are discussed.
DPC4 gene in various tumor types. (1996)

We recently identified a novel tumor-suppressor gene, DPC4, at chromosome 18q21.1 and found that both alleles of DPC4 were inactivated in nearly one-half of the pancreatic carcinomas. Here, we analyzed 338 tumors, originating from 12 distinct anatomic sites, for alterations in the DPC4 gene. Sixty-four specimens were selected for the presence of the allelic loss of 18q and were further analyzed for DPC4 sequence alterations. An alteration of the DPC4 gene sequence was identified in one of eight breast carcinomas and one of eight ovarian carcinomas. These results indicate that whereas DPC4 inactivation is prevalent in pancreatic carcinoma (48%), it is distinctly uncommon (< 10%) in the other tumor types examined. The tissue restriction of alterations in DPC4, as in many other tumor-suppressor genes, emphasizes the complexity of rate-limiting checkpoints in human tumorigenesis.
Psychedelics as anti-inflammatory agents (2018)

Serotonin (5-hydroxytryptamine, 5-HT)<sub>2A</sub> receptor agonists have recently emerged as promising new treatment options for a variety of disorders. The recent success of these agonists, also known as psychedelics, like psilocybin for the treatment of anxiety, depression, obsessive-compulsive disorder (OCD), and addiction, has ushered in a renaissance in the way these compounds are perceived in the medical community and populace at large. One emerging therapeutic area that holds significant promise is their use as anti-inflammatory agents. Activation of 5-HT<sub>2A</sub> receptors produces potent anti-inflammatory effects in animal models of human inflammatory disorders at sub-behavioural levels. This review discusses the role of the 5-HT<sub>2A</sub> receptor in the inflammatory response, as well as highlight studies using the 5-HT<sub>2A</sub> agonist (<i>R</i>)-2,5-dimethoxy-4-iodoamphetamine [(<i>R</i>)-DOI] to treat inflammation in cellular and animal models. It also examines potential mechanisms by which 5-HT<sub>2A</sub> agonists produce their therapeutic effects. Overall, psychedelics regulate inflammatory pathways via novel mechanisms, and may represent a new and exciting treatment strategy for several inflammatory disorders.
Poliovirus RNA-Dependent RNA Polymerase (3Dpol):  Pre-Steady-State Kinetic Analysis of Ribonucleotide Incorporation in the Presence of Mn2+ (2004)

The use of Mn2+ as the divalent cation cofactor in polymerase-catalyzed reactions instead of Mg2+ often diminishes the stringency of substrate selection and incorporation fidelity. We have solved the complete kinetic mechanism for single nucleotide incorporation catalyzed by the RNA-dependent RNA polymerase from poliovirus (3Dpol) in the presence of Mn2+. The steps employed during a single cycle of nucleotide incorporation are identical to those employed in the presence of Mg2+ and include a conformational-change step after nucleotide binding to achieve catalytic competence of the polymerase−primer/template−nucleotide complex. In the presence of Mn2+, the conformational-change step is the primary determinant of enzyme specificity, phosphoryl transfer appears as the sole rate-limiting step for nucleotide incorporation, and the rate of phosphoryl transfer is the same for all nucleotides: correct and incorrect. Because phosphoryl transfer is the rate-limiting step in the presence of Mn2+, it was possible to determine that the maximal phosphorothioate effect in this system is in the range of 8−11. This information permitted further interrogation of the nucleotide-selection process in the presence of Mg2+, highlighting the capacity of this cation to permit the enzyme to use the phosphoryl-transfer step for nucleotide selection. The inability of Mn2+ to support a reduction in the efficiency of phosphoryl transfer when incorrect substrates are employed is the primary explanation for the loss of fidelity observed in the presence of this cofactor. We propose that the conformational change involves reorientation of the triphosphate moiety of the bound nucleotide into a conformation that permits binding of the second metal ion required for catalysis. In the presence of Mg2+, this conformation requires interactions with the enzyme that permit a reduction in catalytic efficiency to occur during an attempt to incorporate an incorrect nucleotide. Adventitious interactions in the cofactor-binding site with bound Mn2+ may diminish fidelity by compensating for interaction losses used to modulate catalytic efficiency when incorrect nucleotides are bound in the presence of Mg2+.
Long‐acting antituberculous therapeutic nanoparticles target macrophage endosomes (2014)

Eradication of Mycobacterium tuberculosis (MTB) infection requires daily administration of combinations of rifampin (RIF), isoniazid [isonicotinylhydrazine (INH)], pyrazinamide, and ethambutol, among other drug therapies. To facilitate and optimize MTB therapeutic selections, a mononuclear phagocyte (MP; monocyte, macrophage, and dendritic cell)-targeted drug delivery strategy was developed. Long-acting nanoformulations of RIF and an INH derivative, pentenyl-INH (INHP), were prepared, and their physicochemical properties were evaluated. This included the evaluation of MP particle uptake and retention, cell viability, and antimicrobial efficacy. Drug levels reached 6 μg/10(6) cells in human monocyte-derived macrophages (MDMs) for nanoparticle treatments compared with 0.1 μg/10(6) cells for native drugs. High RIF and INHP levels were retained in MDM for >15 d following nanoparticle loading. Rapid loss of native drugs was observed in cells and culture fluids within 24 h. Antimicrobial activities were determined against Mycobacterium smegmatis (M. smegmatis). Coadministration of nanoformulated RIF and INHP provided a 6-fold increase in therapeutic efficacy compared with equivalent concentrations of native drugs. Notably, nanoformulated RIF and INHP were found to be localized in recycling and late MDM endosomal compartments. These were the same compartments that contained the pathogen. Our results demonstrate the potential of antimicrobial nanomedicines to simplify MTB drug regimens.
A comparison of prostate knowledge of African-American and Caucasian men: changes from prescreening baseline to postintervention. (1998)

An item-by-item analysis revealed that there was only one test item in which program participation did not "correct" knowledge. African-American men were still more likely to believe that pain was the first symptom that would alert them to the presence of cancer. The screening program included information (both printed and oral content) that emphasized the importance of routine screening to detect cancer at an early stage, because most men would experience no symptoms. The only other reported study that examined knowledge documented similar findings with respect to an understanding of symptomology. These findings can be used to direct or guide the educational component of future screening programs that hope to target African-American men.
Long‐term antidyskinetic efficacy of amantadine in Parkinson's disease (2010)

Several randomized placebo-controlled trials have consistently shown antidyskinetic effects of amantadine in levodopa treated patients with advanced Parkinson's disease (PD). However, all of these were of short duration and there have been claims that the effect of amantadine on levodopa induced dyskinesias (LID's) wear off after about 9 months of treatment. This randomized placebo-controlled parallel-group study was performed to assess the long-term antidyskinetic effect of amantadine in 32 PD patients, who after having been on stable amantadine therapy for LID over at least one year- were switched in a double blind manner to amantadine or placebo and followed for 3 weeks. Dyskinesia duration and intensity were assessed by UPDRS IV items 32 and 33 as well as by patient's diaries. The primary outcome was the score change of UPDRS IV items 32 + 33 between baseline and 3 weeks after treatment as well as the between treatment group comparison of the score change of UPDRS IV items 32 + 33. There was a significant increase of UPDRS IV items 32 + 33 in patients treated with placebo from 3.06 (95% CI, 2.1-4.03) at baseline to 4.28 (95% CI, 3.1-5.4) at three-week follow-up (P = 0.02) compared with no significant change between baseline 3.2 (95% CI, 2.1-4.4) to follow-up 3.6 (95% CI, 2.3-4.8) in patients staying on amantadine. These findings argue for long-term antidyskinetic efficacy of amantadine in PD patients with LID's.