gebhart/patrepeval huggingface dataset:
Restoration of cerebrovascular responsiveness to hyperventilation by the oxygen radical scavenger n-acetylcysteine following experimental traumatic brain injury (1991)

Previous experiments have shown that, following experimental fluid-percussion brain injury, cyclo-oxygenase-dependent formation of oxygen radicals prevents arteriolar vasoconstriction in response to hyperventilation. The oxygen radical scavengers superoxide dismutase and catalase restore normal reactivity; however, they are not routinely available for clinical use. The present study tested whether n-acetylcysteine (Mucomyst), an agent currently available for acetaminophen toxicity, could be used as a radical scavenger to restore reactivity after brain injury. N-acetylcysteine (163 mg/kg) was given intraperitoneally prior to or 30 minutes after fluid-percussion brain injury (2.6 atm) in cats, and reactivity to hyperventilation was tested 1 hour after injury. The authors found either that pre- or postinjury administration led to normal reactivity. Additional experiments supported the hypothesis that n-acetylcysteine is an oxygen radical scavenger, since it reduced or prevented the free radical-dependent cerebral arteriolar dilation normally induced by the topical application of arachidonic acid or bradykinin. The mechanism by which n-acetylcysteine is effective in trauma may involve direct scavenging of radicals or stimulation of glutathione peroxidase activity. The results suggest that n-acetylcysteine may be useful for treatment of oxygen free radical-mediated brain injury.
Future directions in plasminogen activator therapy (1990)

Thrombotic disorders such as myocardial infarction and stroke are the leading causes of death and disability in industrialized nations. Timely institution of thrombolytic therapy can achieve a reduction of infarct size, a preservation of left ventricular function, and a reduction in mortality. The administration of streptokinase, urokinase, and acylated plasminogen-streptokinase activator complex (APSAC) can be associated with a complete breakdown of the hemostatic system. Tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA, prourokinase) are more fibrin specific; however, at the large dosages of activator needed for therapeutic efficacy, bleeding complications are still a problem. New approaches to optimizing the risk/benefit ratio for the patient by improving efficacy without sacrificing specificity include the use of synergistic combinations of plasminogen activators, mutants of t-PA and scu-PA, chimeric molecules, and antibody-targeted thrombolytic agents. The last approach opens the possibility of targeting several different components of the clot with either fibrinolytic or antiplatelet effector functions in one optimized molecule.
Anabolic or Catabolic Responses of MC3T3-E1 Osteoblastic Cells to Parathyroid Hormone Depend on Time and Duration of Treatment (1999)

We have investigated signaling (cAMP) and anabolic responses (mineralization of extracellular matrix [ECM]) to parathyroid hormone (PTH) in long-term (30 days) cultures of MC3T3-E1 cells, a murine model of osteoblast differentiation. Expression of PTH/PTH-related peptide receptor (PTH1R) mRNA is detected early and remains relatively constant for 2 weeks with somewhat higher levels observed during the second half of the culture period. In contrast to the relatively stable PTH1R mRNA expression, the cAMP response to PTH varies markedly with no response at day 5 and a marked response (80-fold versus control) by day 10. Responsiveness to PTH remains elevated with fluctuations of 30- to 80-fold stimulation throughout the remainder of the culture period. The timing and duration of PTH treatment to achieve in vitro mineralization of ECM was evaluated. When continuous PTH treatment was initiated before day 20, mineralization decreased. If continuous PTH treatment began on or after day 20, mineralization was unaffected. However, if treatment began on day 20 and then stopped on day 25, mineralization on day 30 was increased 5-fold. This mineralization response to intermittent PTH was confirmed in primary cultures of murine and human osteoblastic cells. These data provide a potential basis for understanding the differential responses to PTH (anabolic versus catabolic) and indicate the developmental temporal variance of anabolic and catabolic responses. Since cAMP signaling was relatively unchanged during this interval (day 10-30) and stimulation of adenylate cyclase only partially mimicked the PTH effect on increased mineralization, other signaling pathways are likely to be involved in order to determine the specific anabolic response to short-term PTH treatment during the differentiation process.
Alteration of Trichostrongylus colubriformis Egg Permeability by Bacillus thuringiensis israelensis Toxin (1987)

A toxin from the bacterium Bacillus thuringiensis israelensis is lethal to nematode eggs. Exposure of eggs of the ruminant nematode Trichostrongylus colubriformis to the toxin significantly increased the eggs' permeability to radiolabeled phenylalanine within 2 hr. Calcium chloride inhibited the toxin-induced change in egg permeability. Iodine staining of eggs that were exposed to the microbial toxin revealed that egg permeability was altered within 5 min and was dependent on the dose of toxin. Addition of 34 mM sucrose, 17 mM sodium chloride, or 17 mM potassium chloride to the eggs' medium increased the toxin's lethality. Exopeptidase activity in eggs of T. colubriformis was reduced significantly after exposure to the B. t. israelensis toxin. Tetrodotoxin, tetraethylammonium chloride, ouabain, 4-acetamido-4'-isothiocyano-stilbene-2,2'disulfonic acid (SITS), 4,4'-diisothiocyano-2,2'disulfonic acid stilbene (DIDS), valinomycin, and sodium vanadate, which affect membrane transport, had no significant effect on the activity of B. t. israelensis toxin for eggs. Likewise, a series of nucleotides and their derivatives had no effect on the toxin's activity. Ovicidal activity of the microbial toxin was increased by 4-aminopyridine (4.4 X), but was decreased by furosemide (97 X), nigericin (263 X), or monensin (125 X). Microscopic measurement of T. colubriformis eggs after treatment with the microbial toxin revealed no significant size change.
Selection of Functional Human Sperm with Higher DNA Integrity and Fewer Reactive Oxygen Species (2014)

Fertilization and reproduction are central to the survival and propagation of a species. Couples who cannot reproduce naturally have to undergo in vitro clinical procedures. An integral part of these clinical procedures includes isolation of healthy sperm from raw semen. Existing sperm sorting methods are not efficient and isolate sperm having high DNA fragmentation and reactive oxygen species (ROS), and suffer from multiple manual steps and variations between operators. Inspired by in vivo natural sperm sorting mechanisms where vaginal mucus becomes less viscous to form microchannels to guide sperm towards egg, a chip is presented that efficiently sorts healthy, motile and morphologically normal sperm without centrifugation. Higher percentage of sorted sperm show significantly lesser ROS and DNA fragmentation than the conventional swim-up method. The presented chip is an easy-to-use high-throughput sperm sorter that provides standardized sperm sorting assay with less reliance on operators's skills, facilitating reliable operational steps.
CD4 T Cell Immunity Is Critical for the Control of Simian Varicella Virus Infection in a Nonhuman Primate Model of VZV Infection (2011)

Primary infection with varicella zoster virus (VZV) results in varicella (more commonly known as chickenpox) after which VZV establishes latency in sensory ganglia. VZV can reactivate to cause herpes zoster (shingles), a debilitating disease that affects one million individuals in the US alone annually. Current vaccines against varicella (Varivax) and herpes zoster (Zostavax) are not 100% efficacious. Specifically, studies have shown that 1 dose of varivax can lead to breakthrough varicella, albeit rarely, in children and a 2-dose regimen is now recommended. Similarly, although Zostavax results in a 50% reduction in HZ cases, a significant number of recipients remain at risk. To design more efficacious vaccines, we need a better understanding of the immune response to VZV. Clinical observations suggest that T cell immunity plays a more critical role in the protection against VZV primary infection and reactivation. However, no studies to date have directly tested this hypothesis due to the scarcity of animal models that recapitulate the immune response to VZV. We have recently shown that SVV infection of rhesus macaques models the hallmarks of primary VZV infection in children. In this study, we used this model to experimentally determine the role of CD4, CD8 and B cell responses in the resolution of primary SVV infection in unvaccinated animals. Data presented in this manuscript show that while CD20 depletion leads to a significant delay and decrease in the antibody response to SVV, loss of B cells does not alter the severity of varicella or the kinetics/magnitude of the T cell response. Loss of CD8 T cells resulted in slightly higher viral loads and prolonged viremia. In contrast, CD4 depletion led to higher viral loads, prolonged viremia and disseminated varicella. CD4 depleted animals also had delayed and reduced antibody and CD8 T cell responses. These results are similar to clinical observations that children with agammaglobulinemia have uncomplicated varicella whereas children with T cell deficiencies are at increased risk of progressive varicella with significant complications. Moreover, our studies indicate that CD4 T cell responses to SVV play a more critical role than antibody or CD8 T cell responses in the control of primary SVV infection and suggest that one potential mechanism for enhancing the efficacy of VZV vaccines is by eliciting robust CD4 T cell responses.
Influence of the mouse major histocompatibility complex, H-2, on liver adenylate cyclase activity and on glucagon binding to liver cell membranes (1980)

The major histocompatibility complex of mice, the H-2 complex, regulates the steady-state level of adenosine cyclic 3',5'-monophosphate (cAMP) in liver. This effect of H-2 may be due to an effect on hormone binding to receptors. Here we show that liver membranes from animals of different H-2 types differ in their sensitivity to glucagon stimulation of adenylate cyclase and in the affinity of their receptors for glucagon. No H-2-associated differences are seen in basal, NaF-stimulated, or GMP-PNP-stimulated adenylate cyclase.
Fluorescence Spectroscopy of Proteins (1968)

Fluorescence spectroscopy of proteins, analyzing polarity, distances between groups, flexibility and conformational transitions
Graphitic Nanoribbons with Dibenzo[e,l]pyrene Repeat Units: Synthesis and Self-Assembly (2009)

A novel homologous series of five monodisperse ribbon-type polyphenylenes, with rigid dibenzo[e,l]pyrene cores in the repeat units, are synthesized by a microwave-assisted Diels−Alder reaction. The size of the obtained polyphenylene ribbons ranges from 132 to 372 carbon atoms in the aromatic backbone which incorporates up to six dibenzo[e,l]pyrene units, thus showing quite different aspect ratios. Because of the flexibility of the backbone and the peripheral substitution with dodecyl chains, the polyphenylene ribbons are well soluble in organic solvents and can be fully characterized by standard analytical techniques. Their unique structure is especially designed to produce a series of giant ribbon-type polycyclic aromatic hydrocarbons (PAHs) in a single further reaction step by cyclodehydrogenation. Therefore, the incorporated dibenzo[e,l]pyrene cores are an important feature because they facilitate the dehydrogenation and improve the reaction yields. The smallest representative of the completely dehydrogenated planarized (2D) PAH ribbons, prepared from the polyphenylene ribbon with 132 aromatic carbon atoms, is still sufficiently soluble and shows a λmax value of 644 nm. Most importantly, these graphitic molecules self-organize into 2D columns when adsorbed on highly oriented pyrolytic graphite (HOPG), thus rendering them attractive candidates for future applications in organic electronic devices such as e.g. field effect transistors. A deeper insight into possible conformations of the sterically demanding side chains and their influence on the packing behavior of such giant PAHs into columnar arrangements is additionally obtained by molecular dynamics simulations. Using Marcus theory for a nonadiabatic temperature-activated charge transfer, we discuss the advantages of an extended, anisotropic in shape, π-system as compared to traditional one-dimensional molecular arrangements of typical discotics.
Inactivation of p53 enhances sensitivity to multiple chemotherapeutic agents. (1996)

Many tumor types have p53 and/or RB mutations, and it is unclear what role the mutations of these tumor suppressor genes have on the efficacy of chemotherapeutic agents. The effect of p53 and RB inactivation on sensitivity to chemotherapeutic drugs was examined using a model system in which p53 or RB was inactivated in normal human foreskin fibroblasts (HFFs) by acute expression of human papillomavirus (HPV) 16E6 or 16E7. Cytotoxicity assays showed that HFFs expressing HPV 16E6 were 6- to 9-fold more sensitive to the DNA crosslinkers cisplatin and carboplatin and 7.8- to 11.5-fold more sensitive to the tubulin polymerizing agent paclitaxel than were LXSN-expressing cells. Analysis of mouse embryonal fibroblasts lacking p53 (p53-/-) compared with mouse embryonal fibroblasts homozygous (p53+/+) and heterozygous (p53+/-) for wild-type p53 confirmed the role of p53 in the enhanced sensitivity to cisplatin. Treatment with the alkylating agents melphalan and nitrogen mustard resulted in 3.8- to 7.3-fold greater sensitivity in HPV 16E6- or 16E7-expressing cells compared with LXSN-expressing cells. Enhanced sensitivity to cisplatin in cells lacking p53 function was explored by examination of its effects on cell cycle progression after exposure. When treated with cisplatin, HFFs expressing 16E6 showed delayed progression through S phase relative to HFFs expressing LXSN. The delay in S phase progression was coincident with the induction of p53 protein levels in LXSN-containing HFFs, suggesting a role for p53 in DNA repair of cisplatin-induced damage. These results indicate that the inactivation of p53 in the absence of other genetic alterations leads to enhanced sensitivity to multiple chemotherapeutic agents rather than to increased resistance.
Comparative Study of the Properties of the Purified Internal and External Invertases from Yeast (1968)

The properties of purified preparations of the internal and external invertases of yeast, designated by their location relative to the cell membrane, show similarities and marked disparities. The molecular weight and the specific activity of the internal enzyme are similar to those of the protein moiety of the external, but their amino acid compositions differ. The external invertase contains cystine or cysteine, and the internal enzyme does not, but neither is activated by cysteine. If the disparities in amino acid composition reflect enzymes that are aggregates of different subunits, at least one of which is identical in the two enzymes, the close similarities of all the other properties would then suggest a precursor-product relationship. The internal enzyme contains little or no carbohydrate, whereas the external invertase is a glycoprotein containing 50% mannan and 3% glucosamine. The latter probably links the protein with the carbohydrate moiety. Both invertases have the same Km for sucrose and raffinose, and neither shows an appreciable transferase activity. The pH optimum for enzymatic activity is the same, but their pH-stability curves differ, the internal invertase showing reversible inactivation at acid pH. The internal invertase has a higher mobility than the external in polyacrylamide gel electrophoresis at pH 6.8 and 8.6. The enzymes are immunologically related, and sucrose-negative mutants lack both external and internal invertase activity.
New aspects of the renin–angiotensin system: angiotensin-converting enzyme 2 – a potential target for treatment of hypertension and diabetic nephropathy (2008)

Angiotensin-converting enzyme 2 is a key enzyme in the renin-angiotensin system that favors the degradation of angiotensin I and angiotensin II. Angiotensin-converting enzyme 2 inhibition by pharmacological means and by genetic deletion worsens kidney disease in diabetic mice. Strategies geared to increasing angiotensin-converting enzyme 2 activity may provide a novel therapeutic target within the renin-angiotensin system by enhancing angiotensin II degradation that may complement the current approach of inhibiting angiotensin II formation and action. Amplifying angiotensin-converting enzyme 2 activity may have a potential therapeutic role for kidney disease and hypertension.
Short-term outcome of kidney transplants from non-heart-beating donors after preservation by machine perfusion (1996)

Abstract In this study, the short-term outcome of renal transplants from non-heart-beating donors (NHBD) preserved by machine perfusion (MP) is evaluated and compared to preservation by cold storage (CS). Twenty-two NHBD kidneys were procured during 1993 and 1994 after in situ perfusion with his-tidine-tryptophan ketoglutarate and preserved by continuous perfusion using University of Wisconsin organ preservation solution for MP as a perfusate. Between 1980 and 1992, 57 NHBD kidneys were procured and preserved by CS. Donors in the MP group sustained increased first warm ischemia times (WITI) (P < 0.1) and recipients in the MP group suffered longer anastomosis time, worse HLA-DR mismatch, and more initial use of cyclosporin as immunosuppressant; all these factors are known to be deleterious to short-term outcome. Despite these unfavorable conditions, delayed function (DF) rate was decreased in the MP group, although not significantly. However, when considering only kidneys with WI ± 45 min, short-term outcome was significantly better in the MP group (P < 0.05). We conclude that MP is superior for the preservation of NHBD kidneys, especially after prolonged warm ischemia.
Components of microtubular structures in Saccharomyces cerevisiae. (1986)

Most studies of cytoskeletal organelles have concentrated on molecular analyses of abundant and biochemically accessible structures. In many of the classical cases, however, the nature of the system chosen has precluded a concurrent genetic analysis. The mitotic spindle of the yeast Saccharomyces cerevisiae is one example of an organelle that can be studied by both classical and molecular genetics. We show here that this microtubule structure also can be examined biochemically. The spindle can be isolated by selective extractions of yeast cells by using adaptations of methods successfully applied to animal cells. In this way, microtubule-associated proteins of the yeast spindle are identified.
Real-Time Specific Energy Monitoring Reveals Drilling Inefficiency and Enhances the Understanding of When to Pull Worn PDC Bits (2002)

Abstract Optimizing when to replace worn bits can yield substantial cost savings, especially in the high cost deep water offshore drilling fields, however, recognizing when a bit is "dull" and past its true economic life can be difficult. All too often, speculation and the hope that the bit will "break through" into something more drillable has remained the driving force for determining whether to change a bit or leave it in the hole. This decision making process is extremely inefficient and does not further the philosophy on continuous improvement. The concept developed to dramatically improve this inefficient decision process involved measuring the mechanical energy input at the drill rig floor; calculating the drilling specific energy; checking current formation type via real-time downhole gamma ray readings; comparing the specific energy with the benchmark new bit specific energy and then using these values to assess the bit's "dull" state. This method has been proven to work in synthetic based mud systems where balling does not mask bit dull condition. Since both balled-new bits and dull bits exhibit similar levels of inefficiency, it was imperative the operator proved this process worked in water-based drilling fluids that had replaced earlier synthetic muds. Synthetic muds were replaced by the water-based fluids due to environmental concerns, cost, and improved performance in WBM. Recently, the operator established that this process worked in water based mud systems that are treated with anti-balling chemicals. The case studies where this methodology was developed will be presented and discussed.
Protein NMR Techniques (1997)

In Protein NMR Techniques leading experts demonstrate how to successfully apply the fundamentals of NMR to the study of proteins. They cover not only assignment and structure determination techniques, but also the practical aspects of experimental set-up, protein production, data processing, and binding studies. Extensive treatments of paramagnetics and metalloproteins, membrane-bound proteins, and protein-ligand complexes are also included. Protein NMR Techniques offers a practical blend of in-depth theory and practice, as well as worked-out examples of the use of NMR in studying the properties of proteins. Its focused treatment of proteins make it an indispensable study guide for chemists and biochemists, including both those with only a basic knowledge of NMR, as well as more experienced investigators
Studies on Total Synthesis of the Cytotoxic Marine Alkaloid Agelastatin A (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTStudies on Total Synthesis of the Cytotoxic Marine Alkaloid Agelastatin AGlen T. Anderson, Charles E. Chase, Yung-hyo Koh, Didier Stien, Steven M. Weinreb, and Maoyu ShangView Author Information Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802 Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556 Cite this: J. Org. Chem. 1998, 63, 22, 7594–7595Publication Date (Web):October 13, 1998Publication History Received1 September 1998Published online13 October 1998Published inissue 1 October 1998https://pubs.acs.org/doi/10.1021/jo981785ihttps://doi.org/10.1021/jo981785irapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views1007Altmetric-Citations46LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Alcohols,Amines,Cyclization,Hydrocarbons,Organic compounds Get e-Alerts