gebhart/patrepeval huggingface dataset:
Investigation of the pathophysiological mechanisms of migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38 (2014)

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) and vasoactive intestinal polypeptide are structurally and functionally closely related but show differences in migraine-inducing properties. Mechanisms responsible for the difference in migraine induction are unknown. Here, for the first time, we present a head-to-head comparison study of the immediate and long-lasting observations of the migraine-inducing, arterial, physiological and biochemical responses comparing PACAP38 and vasoactive intestinal polypeptide. In a double-blind crossover study 24 female migraine patients without aura were randomly allocated to intravenous infusion of PACAP38 (10 pmol/kg/min) or vasoactive intestinal polypeptide (8 pmol/kg/min) over 20 min. We recorded incidence of migraine during and after infusion (0-24 h). Magnetic resonance angiography of selected extra- and intracranial arteries, blood samples (plasma PACAP38 and vasoactive intestinal polypeptide and serum tryptase), and vital signs (blood pressure, heart rate, respiratory frequency, and end-tidal pressure of CO2) was recorded before and up to 5 h after infusion. Twenty-two patients [mean age 24 years (range 19-36)] completed the study on both days. Sixteen patients (73%) reported migraine-like attacks after PACAP38 and four after vasoactive intestinal polypeptide (18%) infusion (P = 0.002). Three of four patients, who reported migraine-like attacks after vasoactive intestinal polypeptide, also reported attacks after PACAP38. Both peptides induced marked dilatation of the extracranial (P &lt; 0.05), but not intracranial arteries (P &gt; 0.05). PACAP38-induced vasodilatation was longer lasting (&gt;2 h), whereas vasoactive intestinal polypeptide-induced dilatation was normalized after 2 h. We recorded elevated plasma PACAP38 at 1 h after the start of PACAP38 infusion only in those patients who later reported migraine attacks. Blood levels of vasoactive intestinal polypeptide and tryptase were unchanged after PACAP38 infusion. In conclusion, PACAP38-induced migraine was associated with sustained dilatation of extracranial arteries and elevated plasma PACAP38 before onset of migraine-like attacks. PACAP38 has a much higher affinity for the PAC1 receptor and we therefore suggest that migraine induction by PACAP38 may be because of activation of the PAC1 receptor, which may be a future anti-migraine drug target.
Functional, endogenously expressed 5‐hydroxytryptamine 5‐ht7 receptors in human vascular smooth muscle cells (1996)

Human uterine artery smooth muscle cells in culture were shown to express constitutively both 5-ht7 receptor mRNA and 5-ht7-like receptors functionally linked to cyclic AMP formation. 5-Carboxamidotryptamine (5-CT) and 5-HT enhanced forskolin-stimulated cyclic AMP accumulation in these cells, with pEC50 values of 7.12 and 6.25, sumatriptan being very weakly active. Both methiothepin (0.1 microM) and clozapine (1 microM), but not the 5-HT4-receptor antagonist, SDZ 205-557 (10 microM) antagonized the effects of 5-CT. In reverse transcriptase-polymerase chain reaction analysis, the mRNA for 5-ht7, but not for 5-HT4 or 5-ht6 receptors was found to be strongly expressed in the same cells. These findings represent a further step toward the recognition of 5-ht7 receptors as real, functional receptors.
U.S. Department of Energy Illness, and Injury Surveillance Program, Worker Health At A Glance, 1995-2004 (2007)

The Department of Energy’s (DOE) Illness and Injury Surveillance Program (IISP) has monitored the health of contractor workers at selected DOE sites since 1990. For the first time, the IISP has sufficient data to describe, in a collective manner, the health trends occurring among workers at a number of DOE sites during a 10-year period. This brief report and the more detailed Worker Health Summary assess illness and injury trends of DOE workers according to gender, age, occupational group, and program office over the 10-year period, 1995 through 2004. During this time, over 137,000 individual contractor workers were employed at the 15 DOE sites participating in the IISP.
Isolation and characterization of the rat proenkephalin gene. (1984)

The rat proenkephalin gene has been isolated by molecular cloning and characterized by DNA-sequence analysis. The gene exhibits a structural organization similar to that of the human gene. The nucleotide sequence encoding the biologically active opioid peptides which are generated from the proenkephalin precursor as well as the 3' untranslated region of the mRNA are found on a large exon at the 3' end of the gene (Exon III). The nucleotide sequence encoding the N terminus of the mature protein and its signal peptide are located on Exon II while Exon I encodes the 5' untranslated region of the mRNA. The nucleotide sequence of these exons and their flanking regions has been determined and compared to the human proenkephalin gene. Analysis of the nucleotide sequence homology between the human and rat proenkephalin gene reveals the presence of highly conserved regions within both the coding and noncoding portions of the genes. Enkephalin-coding sequences as well as 5' flanking sequences appear to be the most highly conserved. The importance and possible function of these sequences are discussed.
The IE2 60-Kilodalton and 40-Kilodalton Proteins Are Dispensable for Human Cytomegalovirus Replication but Are Required for Efficient Delayed Early and Late Gene Expression and Production of Infectious Virus (2007)

The human cytomegalovirus (HCMV) IE2 86-kDa protein is an essential transactivator of viral and cellular gene expression. Additional proteins of 60 and 40 kDa are expressed from the IE2 gene at late times postinfection and are identical to the C terminus of IE2 86. We have constructed HCMV recombinants that express wild-type full-length IE2 86 but do not express the IE2 40- and 60-kDa proteins. Each of these recombinants is viable, indicating that neither the 60-kDa nor the 40-kDa protein is required for virus replication, either alone or in combination. Cells infected with the IE2 60 and IE2 40 deletion mutants, however, exhibit decreased expression of selected viral genes at late times. In particular, expression of the viral DNA replication factor UL84 is affected by the deletion of IE2 40, and expression of the tegument protein pp65 (ppUL83) is affected by the deletion of both IE2 40 and IE2 60. IE2 60 and IE2 40 are also required for the production of normal levels of infectious virus. Finally, IE2 40 appears to function as a repressor of major immediate-early transcription in the infected cell. These results begin to define functions for the IE2 60- and IE2 40-kDa proteins and indicate that these products contribute both to the expression of selected viral genes and to the overall progression of the infection.
A Nested Model for Visualization Design and Validation (2009)

We present a nested model for the visualization design process with four layers: characterize the problem domain, abstract into operations on data types, design visual encoding and interaction techniques, and create algorithms to execute techniques efficiently. The output from a level above is input to the level below, bringing attention to the design challenge that an upstream error inevitably cascades to all downstream levels. This model provides prescriptive guidance for determining appropriate evaluation approaches by identifying threats to validity unique to each level. We call attention to specific steps in the design and evaluation process that are often given short shrift. We also provide three recommendations motivated by this model:authors should distinguish between these levels when claiming contributions at more than one of them, authors should explicitly state upstream assumptions at levels above the focus of a paper, and visualization venues should accept more papers on domain characterization.
Synthesis and biological activity of derivatives of glycopeptide antibiotics eremomycin and vancomycin nitrosated, acylated or carbamoylated at the N-terminal. (1993)

Nitrosation, carbamoylation or acylation of the glycopeptide antibiotics eremomycin or vancomycin produced series of derivatives substituted at the N-terminus of the peptides. Though the modified amino group in these derivatives is not capable of protonation, N-nitroso derivatives retain antibacterial activity in vitro and in vivo. N-Carbamoyleremomycin has low activity, and N-Cbz-eremomycin and N-Boc-eremomycin are devoid of antibacterial activity, both in vitro and in vivo.
Excitation wavelength dependence of terahertz emission from InN and InAs (2006)

The authors report on the excitation wavelength dependence of terahertz emission from n-InN and bulk p-InAs pumped with femtosecond pulses tunable from 800to1500nm. The terahertz amplitude, normalized to pump and probe power, from both narrow band gap semiconductors remains relatively constant over the excitation wavelength range. In addition, terahertz radiation from In- and N-face InN samples with bulk carrier concentrations ranging from 1017to1019cm−3 is also investigated, showing a strong dependence of terahertz emission on bulk carrier concentration. The experimental results agree well with calculations based on drift-diffusion equations incorporating momentum conservation and relaxation.
Twice‐daily compared with once‐daily insulin glargine in people with Type 1 diabetes using meal‐time insulin aspart (2006)

Blood glucose concentration rises in the late afternoon in association with falling plasma insulin levels towards the end of the 24-h period after insulin glargine injection in some people with Type 1 diabetes using once-daily glargine at dinner-time plus a rapid-acting insulin analogue at meal-times. This is prevented by twice-daily injection of insulin glargine.
Molecular Mechanisms Mediating Inflammation in Vascular Disease (2003)

There are several clinical challenges for the treatment of intractable cardiovascular diseases, including restenosis, atherosclerotic complications resulting from plaque rupture, severe tissue ischemia, and heart failure. Emerging evidence suggests that an inflammatory process is involved in the pathogenesis of such intractable diseases. In particular, inflammatory responses to arterial injury, which cause continuous recruitment and activation of monocytes mainly through activation of the monocyte chemoattractant protein-1 (MCP-1) pathway, have a central role in restenosis and atherogenesis. We recently devised a new strategy for anti-MCP-1 therapy by transfecting an N-terminal deletion mutant of the MCP-1 gene into skeletal muscles. This mutant MCP-1 lacks the N-terminal amino acids 2 to 8, called 7ND, and works as a dominant-negative inhibitor of MCP-1. We demonstrated that 7ND gene transfer suppresses monocyte infiltration/activation after arterial injury and markedly inhibits experimental restenosis in animals after balloon injury or stent placement. Furthermore, 7ND gene transfer not only attenuated the development of early atherosclerotic lesions but also limited progression of preexisting atherosclerotic lesions and changed the lesion composition into a more stable phenotype in hypercholesterolemic mice. Vascular inflammation mediated by MCP-1 might create a positive feedback loop to enhance restenotic and atherosclerotic changes through activating lesional monocytes. Therefore, vascular inflammation mediated by MCP-1 has a central role in the development of experimental restenosis, atherosclerosis, and plaque destabilization, leading to acute coronary syndrome. This strategy for gene therapy might be useful against human restenosis, thereby opening a new therapeutic window for antirestenosis and antiatherosclerosis paradigms.
Pixel and Edge Based Illuminant Color Estimation for Image Forgery Detection (2015)

Images are one of the powerful media for communication. Image security is a main issue in the fields that using digital images. By the development of high resolution cameras, personal computers and photo-editing software's, the manipulation of images is becoming common. This paper mainly focuses on common form of image manipulation such as image splicing. The process of analysis is done with the help of inconsistencies in illuminant color of images. Illumination inconsistencies detection is a powerful way for image forgery detection. Inconsistency detection among different images can be identified with the help of pixel and edge based illuminant color estimation on image regions. From these illuminant estimators, extract shape and color features, which is then provided to a classifier for making decision. Classification using SVM and its performance is evaluated using distinct testing process. The main contribution of this method is, how illuminant color estimation on various constraints can be exploited as a forgery detection method and how these are provided for decision-making with minimal user interaction.
Novel amplification of DNA in a hairpin structure: towards a radical elimination of PCR errors from amplified DNA (2003)

Errors introduced during PCR amplification set a selectivity limit for microsatellite analysis and molecular mutation detection methods since polymerase misincorporations invariably get confused with genuine mutations. Here we present hairpin-PCR, a new form of PCR that completely separates genuine mutations from polymerase misincorporations. Hairpin-PCR operates by converting a DNA sequence to a hairpin following ligation of oligonucleotide caps to DNA ends. We developed conditions that allow a DNA hairpin to be efficiently PCR-amplified so that, during DNA synthesis, the polymerase copies both DNA strands in a single pass. Consequently, when a misincorporation occurs it forms a mismatch following DNA amplification, and is distinguished from genuine mutations that remain fully matched. Error-free DNA can subsequently be isolated using one of many approaches, such as dHPLC or enzymatic depletion. We present feasibility for the main technical steps involved in this new strategy, conversion of a sequence to a hairpin that can be PCR-amplified from human genomic DNA, exponential amplification from picogram amounts, conversion of misincorporations to mismatches and separation of homoduplex from heteroduplex hairpins using dHPLC. The present hairpin-PCR opens up the possibility for a radical elimination of PCR errors from amplified DNA and a major improvement in mutation detection.
Ponatinib (AP24534), a Multitargeted Pan-FGFR Inhibitor with Activity in Multiple FGFR-Amplified or Mutated Cancer Models (2012)

Members of the fibroblast growth factor receptor family of kinases (FGFR1-4) are dysregulated in multiple cancers. Ponatinib (AP24534) is an oral multitargeted tyrosine kinase inhibitor being explored in a pivotal phase II trial in patients with chronic myelogenous leukemia due to its potent activity against BCR-ABL. Ponatinib has also been shown to inhibit the in vitro kinase activity of all four FGFRs, prompting us to examine its potential as an FGFR inhibitor. In Ba/F3 cells engineered to express activated FGFR1-4, ponatinib potently inhibited FGFR-mediated signaling and viability with IC(50) values <40 nmol/L, with substantial selectivity over parental Ba/F3 cells. In a panel of 14 cell lines representing multiple tumor types (endometrial, bladder, gastric, breast, lung, and colon) and containing FGFRs dysregulated by a variety of mechanisms, ponatinib inhibited FGFR-mediated signaling with IC(50) values <40 nmol/L and inhibited cell growth with GI(50) (concentration needed to reduce the growth of treated cells to half that of untreated cells) values of 7 to 181 nmol/L. Daily oral dosing of ponatinib (10-30 mg/kg) to mice reduced tumor growth and inhibited signaling in all three tumor models examined. Importantly, the potency of ponatinib in these models is similar to that previously observed in BCR-ABL-driven models and plasma levels of ponatinib that exceed the IC(50) values for FGFR1-4 inhibition can be sustained in patients. These results show that ponatinib is a potent pan-FGFR inhibitor and provide strong rationale for its evaluation in patients with FGFR-driven cancers.
Studies of Polystyrene-based Ion Exchange Fiber. I. The Preparation and Fundamental Characteristics of Polystyrene-based Ion Exchange Fiber (1983)

Abstract A polystyrene-based ion exchange fiber which has a large ion exchange capacity (ca. 2.5 mequiv g−1) and a high mechanical strength (ca. 1.4 g d−1) has first been prepared by using an islands-in-a-sea type composite fiber, the sea ingredient predominantly comprised of polystyrene for ion exchange and the island ingredient comprised of fiber-forming polypropylene for reinforcement, as the starting material; it can be used in an arbitrary form. It was found that the resulting fiber has two fundamental characteristics; the ion exchange rate for metal ions is extremely high, and the capacity of adsorbing the macromolecular ionic substance is exceedingly large, compared with ordinary ion exchange resins. The diffusion equation of ion exchange in the case of a cylindrical, endless fiber was solved by a modification of the method used for a spherical resin in a simple system. The former results are interpreted in terms of their solutions for two limiting cases. The latter results are explained by the fact that the surface-area ratio of the fiber to the resin is about ten.
Rapid transferrin efflux from brain to blood across the blood–brain barrier (2001)

The brain efflux index method is used to examine the extent to which transferrin effluxes from brain to blood across the blood-brain barrier (BBB) following intracerebral injection. Whereas high-molecular-weight dextran is nearly 100% retained in brain for up to 90 min after intracerebral injection in the Par2 region of the parietal cortex of brain, there is rapid efflux of transferrin from brain to blood across the BBB. The efflux of apotransferrin is 3.5-fold faster than the efflux of holo-transferrin. The brain to blood efflux of apotransferrin is completely saturable by unlabeled transferrin, but is not inhibited by other plasma proteins. These studies provide evidence for reverse transcytosis of transferrin from brain to blood across the BBB. As circulating transferrin is known to undergo transcytosis across the BBB in the blood-to-brain direction, these studies support the model of bidirectional transcytosis of transferrin through the BBB in vivo.
Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. (2007)

Among patients with impaired glucose tolerance or type 2 diabetes, rosiglitazone use for at least 12 months is associated with a significantly increased risk of myocardial infarction and heart failure, without a significantly increased risk of cardiovascular mortality.
Graphene-Based Plasmonic Platform for Reconfigurable Terahertz Nanodevices (2014)

We propose here a new platform to realize a plethora of graphene-based plasmonic nanodevices for frequency-agile terahertz (THz) frontend circuits. We demonstrate that a class of hybrid electronic-plasmonic nanodevices combining active graphene field-effect transistors (GFET) and graphene plasmonic waveguides (GPWG) supporting tightly confined propagation of THz signals, with tailored phase velocity and characteristic impedance controlled by the gate and drain voltages of GFET. We propose a variety of reconfigurable graphene-based nanodevices based on this general architecture, including reconfigurable and electronically programmable phase-shifters, filters, transformers, modulators, and terminators. We envision the integration of these THz circuit elements into a fully reconfigurable THz system as a fundamental step toward new design architectures and protocols for THz communication, sensing, actuation, and biomedical applications.
A Family of Active Iridium Catalysts for Transfer Hydrogenation of Ketones (2006)

The air-stable iridium chlorodihydride complex IrH2Cl[(iPr2PC2H4)2NH], 1, was prepared from the reaction of [IrCl(coe)2]2 with the pincer ligand (iPr2PC2H4)2NH in 2-propanol at 80 °C. Reaction of 1 with KOtBu in THF resulted in the formation of the air-sensitive amidodihydride complex IrH2[(iPr2PC2H4)2N], 2, which in the presence of 2-propanol readily forms the moderately air-stable trihydride complex IrH3[(iPr2PC2H4)2NH], 3. The trihydride and amidodihydride complexes in the absence of a base are exceptionally active catalysts for the transfer hydrogenation of ketones in 2-propanol.
Advances in targeted therapy for acute myeloid leukaemia (2017)

In the past few years, research in the underlying pathogenic mechanisms of acute myeloid leukaemia (AML) has led to remarkable advances in our understanding of the disease. Cytogenetic and molecular aberrations are the most important factors in determining response to chemotherapy as well as long-term outcome, but beyond prognostication are potential therapeutic targets. Our increased understanding of the pathogenesis of AML, facilitated by next-generation sequencing, has spurred the development of new compounds in the treatment of AML, particularly the creation of small molecules that target the disease on a molecular level. Various new agents, such as tyrosine kinase inhibitors, immune checkpoint inhibitors, monoclonal or bispecific T-cell engager antibodies, metabolic and pro-apoptotic agents are currently investigated within clinical trials. The highest response rates are often achieved when new molecularly targeted therapies are combined with standard chemotherapy. Presented here is an overview of novel therapies currently being evaluated in AML.
Capsular polysaccharide types 5 and 8 of Staphylococcus aureus bind specifically to human epithelial (KB) cells, endothelial cells, and monocytes and induce release of cytokines (1995)

In order to examine the possible implication of capsular polysaccharide (CP) types 5 and 8 (CP5 and CP8) from Staphylococcus aureus in the pathological mechanism associated with staphylococcal infections, we tested the immunomodulatory effects of CP5 and CP8 on human epithelial KB cells, endothelial cells, and monocytes. Using biotinylated CP5 and CP8, we provide evidence that both CPs bind to KB cells, endothelial cells, and monocytes in a dose- and calcium-dependent manner through specific interactions. These results were confirmed by competition experiments using soluble cell extracts. Furthermore, we show that CPs bind to identical cell membrane receptors on all three types of human cells and that human normal serum contains a factor(s) which inhibits the binding of both CPs to human KB cells, endothelial cells, and monocytes. The ability of CP5 and CP8 to stimulate the production of cytokines by the human cells was then examined. CP5 and CP8 trigger KB cells to produce interleukin-8 (IL-8); endothelial cells to produce IL-8 and IL-6; and monocytes to produce IL-8, IL-6, IL-1 beta, and tumor necrosis factor alpha. The release of cytokines by all three types of cells is time dependent and dose dependent, and the tumor necrosis factor alpha production by monocytes is not affected by the addition of polymyxin B. We further confirm that human normal serum inhibits the immunomodulatory effects of both polysaccharides on each kind of cell. These results confirm that S. aureus CPs act as bacterial adhesins having immunomodulatory effects for human cells.