gebhart/patrepeval huggingface dataset:
Real Time Pricing and Electricity Markets (2009)

Most US consumers are charged a near-constant retail price for electricity, despite substantial hourly variation in the wholesale market price. This paper evaluates a randomized experiment that exposed households to hourly real time pricing (RTP) and applies the demand estimates to counterfactual simulations in a structural model of the Pennsylvania-Jersey-Maryland electricity market. The model includes a di¤erent approach to the problem of multiple supply function equilibria: I non-parametrically estimate unobservables that rationalize past bidding behavior and use learning algorithms to select …rms ’ counterfactual supply functions. This routine is nested as the second stage of a static entry model that captures an important institution called the Capacity Market, which acts in equilibrium as a minimum constraint on system capacity and transfers the shadow price to capacity owners. There are three central results. First, the experiment’s net e¤ect on consumer behavior was energy conservation during peak hours, not substitution from peak to o¤-peak. Second, large scale RTP would actually increase wholesale electricity prices in peak hours, contrary to predictions from short-run models, while decreasing Capacity Market prices and total entry. Third, although the increased demand elasticity from RTP theoretically reduces producers’ market power, in practice this would be a second-order channel of e ¢ ciency gains. I …nd that through RTP’s combined e¤ects on electricity and Capacity prices, producers ’ and retailers’ pro…ts would be slightly lower, but consumers would realize large welfare gains.
Nonviral Minicircle Generation of Induced Pluripotent Stem Cells Compatible with Production of Chimeric Chickens (2014)

Chickens are vitally important in numerous countries as a primary food source and a major component of economic development. Efforts have been made to produce transgenic birds through pluripotent stem cell [primordial germ cells and embryonic stem cells (ESCs)] approaches to create animals with improved traits, such as meat and egg production or even disease resistance. However, these cell types have significant limitations because they are hard to culture long term while maintaining developmental plasticity. Induced pluripotent stem cells (iPSCs) are a novel class of stem cells that have proven to be robust, leading to the successful development of transgenic mice, rats, quail, and pigs and may potentially overcome the limitations of previous pluripotent stem cell systems in chickens. In this study we generated chicken (c) iPSCs from fibroblast cells for the first time using a nonviral minicircle reprogramming approach. ciPSCs demonstrated stem cell morphology and expressed key stem cell markers, including alkaline phosphatase, POU5F1, SOX2, NANOG, and SSEA-1. These cells were capable of rapid growth and expressed high levels of telomerase. Late-passage ciPSCs transplanted into stage X embryos were successfully incorporated into tissues of all three germ layers, and the gonads demonstrated significant cellular plasticity. These cells provide an exciting new tool to create transgenic chickens with broad implications for agricultural and transgenic animal fields at large.
Progression and regression of atherosclerosis, what roles for LDL-cholesterol and HDL-cholesterol: a perspective (1991)

Numerous observational and intervention studies have shown that total (and LDL) cholesterol levels correlate positively with progression of atherosclerosis. It has also been shown that a mean low HDL cholesterol level is a potent predictor of CHD (coronary heart disease) in populations in which atherosclerotic diseases are prevalent. Recently, studies based on repeat angiographic examination, which are reviewed here, have shed new insight on the different roles that total cholesterol (or LDL) and HDL-cholesterol play on progression and regression of coronary atherosclerosis, respectively. From an epidemiological viewpoint, based on observational as well as intervention studies, the theory emerges that progression correlates best with total (and LDL-) cholesterol and that regression correlates best with HDL-cholesterol. The working hypothesis, if confirmed, will have practical implications for primary and secondary preventive measures.
Identification and characterization of novel salivary thrombin inhibitors from the ixodidae tick, Haemaphysalis longicornis (2003)

Novel antithrombin molecules were identified from the ixodidae tick, Haemaphysalis longicornis. These molecules, named madanin 1 and 2, are 7-kDa proteins and show no significant similarities to any previously identified proteins. Assays using human plasma showed that madanin 1 and 2 dose-dependently prolonged both activated partial thromboplastin time and prothrombin time, indicating that they inhibit both the intrinsic and extrinsic pathways. Direct binding assay by surface plasmon resonance measurement demonstrated that madanin 1 and 2 specifically interacted with thrombin. Furthermore, it was clearly shown that madanin 1 and 2 inhibited conversion of fibrinogen into fibrin by thrombin, thrombin-catalyzed activation of factor V and factor VIII, and thrombin-induced aggregation of platelets without affecting thrombin amidolytic activity. These results suggest that madanin 1 and 2 bind to the anion-binding exosite 1 on the thrombin molecule, but not to the active cleft, and interfere with the association of fibrinogen, factor V, factor VIII and thrombin receptor on platelets with an anion-binding exosite 1. They appear to be exosite 1-directed competitive inhibitors.
Mechanisms of pain in nonmalignant disease (2008)

Inflammatory and neuropathic pain differ considerably in their peripheral mechanisms but certain central spinal and brain mechanisms are common to both. The mechanisms of pain are not fully established but are thought to be underpinned by changes in the expression of receptors (nociceptive plasticity), central spinal hyperexcitability (central sensitization) and alterations in descending control from the midbrain. This review considers these mechanisms and highlights recent advances in the understanding of pain perception.
Evaluating video as a technology for informal communication (1992)

Collaborations in organizations thrive on communication that is informal because informal communication is frequent, interactive, and expressive. Informal communication is crucial for the coordination of work, learning an organization's culture, the perpetuation of the social relations that underlie collaboration, and, in general, any situation that requires communication to resolve ambiguity. Informal communication is traditionally mediated by physical proximity, but physical proximity cannot mediate in geographically distributed organizations. The research described here evaluates the adequacy of a version of a desktop video/audio conferencing system for supporting informal communication in a research and development laboratory. The evaluation took place during a trial in which the system was used by summer employees and their supervisor-mentors. While the system was used frequently, the most common uses and users' assessments suggest that it was used more like a telephone or electronic mail than like physically mediated face-to-face communication. However, some features of its use transcended traditional media and allowed users to gain awareness of their work environment. The paper concludes with a discussion of requirements for successful technology to support informal communication.
From frontotemporal lobar degeneration pathology to frontotemporal lobar degeneration biomarkers (2013)

Frontotemporal dementia (FTD) is an increasingly recognized cause of dementia. This review discusses the different FTD clinical syndromes and frontotemporal lobar degeneration (FTLD) pathological correlates as well as new genetic and proteomic findings that have added to our understanding of FTLD pathogenesis. Various diagnostic modalities including the use of biomarkers will also be addressed. Finally we will highlight future directions in the FTD field. More research is needed to elucidate the cellular mechanisms of neurodegeneration in FTLD and improve clinical diagnostic capabilities.
FLIPS: Hybrid Adaptive Intrusion Prevention (2005)

Intrusion detection systems are fundamentally passive and fail-open. Because their primary task is classification, they do nothing to prevent an attack from succeeding. An intrusion prevention system (IPS) adds protection mechanisms that provide fail-safe semantics, automatic response capabilities, and adaptive enforcement. We present FLIPS (Feedback Learning IPS), a hybrid approach to host security that prevents binary code injection attacks. It incorporates three major components: an anomaly-based classifier, a signature-based filtering scheme, and a supervision framework that employs Instruction Set Randomization (ISR). Since ISR prevents code injection attacks and can also precisely identify the injected code, we can tune the classifier and the filter via a learning mechanism based on this feedback. Capturing the injected code allows FLIPS to construct signatures for zero-day exploits. The filter can discard input that is anomalous or matches known malicious input, effectively protecting the application from additional instances of an attack -- even zero-day attacks or attacks that are metamorphic in nature. FLIPS does not require a known user base and can be deployed transparently to clients and with minimal impact on servers. We describe a prototype that protects HTTP servers, but FLIPS can be applied to a variety of server and client applications.
Novel glucose non-interference biosensor for lactose detection based on galactose oxidase–peroxidase with and without co-immobilised β-galactosidase (2000)

Two types of amperometric biosensors for lactose detection based either on co-immobilisation of two enzymes (galactose oxidase with peroxidase) or co-immobilisation of three enzymes (beta-galactosidase, galactose oxidase and peroxidase) were constructed. A graphite rod with pre-adsorbed ferrocene was used as a working electrode. The use of galactose oxidase instead of the frequently used glucose oxidase resulted in the construction of a glucose-non-interfering lactose sensor. Co-immobilisation of peroxidase with galactose oxidase allowed the effect of borate on the extension of the linear range and the effect of the working potential on galactose oxidase activation to be studied. The presence of beta-galactosidase greatly enhances the sensor's sensitivity, but its linear range is narrower than that of the sensor without beta-galactosidase. Addition of DEAE-dextran and inositol to the enzyme layer improved the half-life more than 16-fold compared with the sensor without stabilisers. A response time between 60 and 75 s (90% of the steady-state value) and a detection limit for lactose determination from 44 to 339 microM (signal-to-noise ratio = 3) were observed depending on the conditions. The precision of measurements of standard lactose solution for the trienzymatic and bienzymatic sensors was 2.19 and 2.02%, respectively. The precision of analysis of dairy products varied from 0.24 to 5.24%. Analyses of real samples showed good correlation with HPLC analysis; eight samples and 10 standard lactose solutions without pre-treatment were analysed in 1 h.
Degradable polyethylenimines as DNA and small interfering RNA carriers (2009)

Gene therapy is a powerful approach in the treatment of a wide range of both inherited and acquired diseases. Nonviral delivery systems have been proposed as safer alternatives to viral vectors because they avoid the inherent immunogenicity and production problems that are seen when viral systems are used. Many cationic polymers, including high-molecular-weight polyethylenimine (PEI) have been widely studied as gene-delivery carriers, both, in vitro and in vivo. However, interest has recently developed in degradable polymeric systems. The advantage of degradable polymer is its low in-vivo cytotoxicity, which is a result of its easy elimination from the cells and body. Degradable polymer also enhances transfection of DNA or small interfering RNA (siRNA) for efficient gene expression or silencing, respectively. This review paper summarizes and discusses the recent advances with degradable PEIs, such as cross-linked and grafted PEIs for DNA and siRNA delivery.
Carbon Monoxide: Innovative Anti-inflammatory Properties of an Age-Old Gas Molecule (2002)

Observations of the effects of carbon monoxide (CO) on mammalian systems have been known for thousands of years. To be sure, CO is deadly under certain conditions and concentrations, but perhaps as the data presented here will make clear, it also possesses other diverse functional and immunomodulatory properties. This review, together with the other reviews in this issue, will detail that over the past three decades, fundamental functional role(s) for this gas molecule are beginning to emerge. This review outlines that at low concentrations, exogenously administered CO is a molecule involved in the regulation of the inflammatory response in a variety of disease models. CO has been shown to modulate such cellular functions as cytokine production, cell proliferation and apoptosis, protecting the lungs and hearts of rodents from such stressors as endotoxin, ischemia/reperfusion injury, cardiac xenograft rejection, and asthma. Although the mechanism by which this simple diatomic gas provides this protection remains obscure, the conclusions are the same: CO at low concentrations, concentrations that are well below those that would otherwise create toxic effects, is proving beneficial in models of acute injury. CO, akin to nitric oxide, is proving to be an extraordinary signaling molecule generated by the cell that is vital in the regulation of cellular homeostasis.
S-Nitrosylation activates Cdk5 and contributes to synaptic spine loss induced by β-amyloid peptide (2011)

The activity of Cdk5 and its regulatory subunit p35 is thought to be important in both normal brain function and neurodegenerative disease pathogenesis. Increased Cdk5 activity, via proteolytic cleavage of p35 to a p25 fragment by the calcium-activated protease calpain or by phosphorylation at Cdk5(Tyr15), can contribute to neurotoxicity. Nonetheless, our knowledge of regulation of Cdk5 activity in disease states is still emerging. Here we demonstrate that Cdk5 is activated by S-nitrosylation or reaction of nitric oxide (NO)-related species with the thiol groups of cysteine residues 83 and 157, to form SNO-Cdk5. We then show that S-nitrosylation of Cdk5 contributes to amyloid-β (Aβ) peptide-induced dendritic spine loss. Furthermore, we observed significant levels of SNO-Cdk5 in postmortem Alzheimer's disease (AD) but not in normal human brains. These findings suggest that S-nitrosylation of Cdk5 is an aberrant regulatory mechanism of enzyme activity that may contribute to the pathogenesis of AD.
Tremelimumab (CP-675,206), a Cytotoxic T Lymphocyte–Associated Antigen 4 Blocking Monoclonal Antibody in Clinical Development for Patients with Cancer (2007)

Tremelimumab (CP-675,206) is a fully human monoclonal antibody specific for human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, CD152) in clinical development for patients with cancer. Blocking the CTLA-4 negative costimulatory receptor with the antagonistic antibody tremelimumab results in immune activation. Administration of tremelimumab to patients with locally advanced and metastatic melanoma has resulted in a subset of patients with durable objective tumor regressions. Its IgG(2) isotype minimizes the possibility of cytotoxic effects on activated T lymphocytes and cytokine release syndrome. Preclinical testing in vitro and in large animal models predicted the target concentrations of circulating antibody in humans necessary for a pharmacodynamic effect. Phase I clinical trials provided evidence of dose- or exposure-related effects consistent with the anticipated mechanism of action. Further clinical development has led to two ongoing registration trials in patients with metastatic melanoma: a phase III randomized trial of tremelimumab versus dacarbazine or temozolomide in previously untreated patients with advanced melanoma and a phase II trial of tremelimumab in previously treated patients with advanced melanoma.
Nanoparticles in Medicine: Therapeutic Applications and Developments (2007)

Nanotechnology is the understanding and control of matter generally in the 1-100 nm dimension range. The application of nanotechnology to medicine, known as nanomedicine, concerns the use of precisely engineered materials at this length scale to develop novel therapeutic and diagnostic modalities. Nanomaterials have unique physicochemical properties, such as ultra small size, large surface area to mass ratio, and high reactivity, which are different from bulk materials of the same composition. These properties can be used to overcome some of the limitations found in traditional therapeutic and diagnostic agents.
Recent Biosynthetic Studies on Antibiotics (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRecent Biosynthetic Studies on AntibioticsKenneth L. Rinehart Jr., Dwight D. Weller, and Cedric J. PearceCite this: J. Nat. Prod. 1980, 43, 1, 1–20Publication Date (Print):January 1, 1980Publication History Published online1 July 2004Published inissue 1 January 1980https://pubs.acs.org/doi/10.1021/np50007a001https://doi.org/10.1021/np50007a001research-articleACS PublicationsRequest reuse permissionsArticle Views245Altmetric-Citations20LEARN 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
Nε-(Carboxymethyl)lysine Protein Adduct Is a Major Immunological Epitope in Proteins Modified with Advanced Glycation End Products of the Maillard Reaction (1996)

Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGE). Recent immunological studies have suggested the potential role of AGE in atherosclerosis, aging, and diabetic complications. We previously prepared a monoclonal (6D12) as well as a polyclonal anti-AGE antibody and proposed the presence of a common AGE structure(s) that may act as a major immunochemical epitope [Horiuchi, S., Araki, N., & Morino, Y. (1991) J. Biol. Chem. 266, 7329-7332]. The purpose of the present study was to determine the major epitope. Amino acid analysis of AGE-proteins indicated that N(epsilon)-(carboxymethyl)lysine (CML) was a major modified lysine residue. Immunologic studies demonstrated the positive reaction of 6D12 not only to all CML-modified proteins tested, but also to BSA modified with several aldehydes known to generate a CML-protein adduct, and a linear correlation between the CML contents of CML-BSA and their immunoreactivity to 6D12 up to approximately 8 mol/mol of protein. Further experiments with CML analogs revealed that the epitope of 6D12 is a CML-protein adduct with an important carbonyl group. In contrast to 6D12, our polyclonal anti-AGE antibody showed a significant but much weaker immunoreactivity to CML-BSA, suggesting that the polyclonal antibody contains two populations, one reactive to CML (CML-PA) and the other unreactive to CML (Non-CML-PA). Non-CML-PA separated from CML-PA by CML-BSA affinity chromatography did not react with all CML-modified preparations, but retained its property to react commonly with AGE preparations obtained from proteins, lysine derivatives, and monoaminocarboxylic acids. Therefore, it is clear that a CML-protein adduct is a major immunological epitope in AGE structures, but there still exist other major epitope(s) expressed commonly in AGE-proteins.
Do Plain Radiographs Correlate With CT for Imaging of Cam-type Femoroacetabular Impingement? (2012)

Level II, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.
Human CDC2-Like Kinase 1 (CLK1): A Novel Target for Alzheimer’s Disease (2014)

The cdc2-like kinases (CLKs) are an evolutionarily conserved group of dual specificity kinases belonging to the CMGC (cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAP kinases), glycogen synthase kinases (GSK) and CDK-like kinases). The CLK family consists of four isoforms namely CLK1, CLK2, CLK3 and CLK4. The human CLK1 encoded protein comprises 454 amino acids and the catalytic domain of CLK1 exhibits the typical protein kinase fold. CLK1 has been shown to autophosphorylate on serine, threonine and tyrosine residues and phosphorylate exogenous substrates on serine and threonine residues. CLK1 plays an important role in the regulation of RNA splicing through phosphorylation of members of the serine and arginine-rich (SR) family of splicing factors. CLK1 is involved in the pathophysiology of Alzheimer's disease by phosphorylating the serine residue in SR proteins. Nuclear speckles of the nucleoplasm contain the stored form of SR proteins and are moderately responsible for the choice of splicing sites during pre-mRNA splicing. Hence, the inhibition of CLK1 can be used as a therapeutic strategy for Alzheimer's disease. Many natural and synthetic molecules are reported to possess CLK1 inhibitory activity. Some specific examples are Marine alkaloid Leucettamine B and KH-CB19. Leucettamine B is a potent inhibitor of CLK1 (15 nM), Dyrk1A (40 nM), and Dyrk2 (35 nM) and a moderate inhibitor of CLK3 (4.5 µM) whereas KH-CB19 is a highly specific and potent inhibitor of the CLK1/CLK4. X-ray crystallographic studies have revealed the binding mode of marine sponge metabolite hymenialdisine and a dichloroindolyl enamino nitrile (KH-CB19) to CLK1. This review focuses on the role of CLKs in the pathophysiology of Alzheimer's disease and therapeutic potential of targeting CLK1 in Alzheimer's disease drug discovery and development. In addition, the recent developments in drug discovery efforts targeting human CLK1 are also highlighted.