gebhart/patrepeval huggingface dataset:
Taurolidine inhibits tumour necrosis factor (TNF) toxicity--new evidence of TNF and endotoxin synergy. (1993)

The use of recombinant tumour necrosis factor (TNF) in the treatment of solid tumours has been limited by life threatening toxicity. In addition TNF may be a major mediator of the effect of endotoxins. Recent evidence suggested that a synergism between endotoxin (at the picogram level) and TNF may contribute to this toxicity. The use of the anti-endotoxin taurolidine may reduce TNF toxicity by interfering with this synergy. C57/BL6 mice (n = 140) received toxic doses (12 micrograms/mouse IV) of TNF. Four groups were studied. Group A received taurolidine 200 mg/kg IV 30 minutes before TNF, group B received TNF followed 30 minutes later by taurolidine 200 mg/kg IV, group C received an identical volume (0.5 ml) of normal saline 30 minutes prior to TNF, and group D taurolidine 200 mg/kg IP 45 minutes before TNF. The mortality rate of those mice receiving intravenous taurolidine 30 minutes prior to TNF was 8.8%. This was significantly less (P < 0.005) than the mortality rate achieved in groups B, C and D (33% vs 39.4% vs 50%). Further experiments employing an MTT (3-(4,5-dimethylthinzol-2-microliters)-2,5-diphenyl tetrazolinm bromide) assay showed that this was not due to direct interaction of taurolidine with TNF but is likely to be due to interference with the synergistic effects of endotoxin and TNF. It was also demonstrated in cotherapy studies in a murine model that taurolidine did not reduce the anti-tumour efficacy of TNF against the TNF sensitive mouse fibrosarcoma cell line Meth-A sarcoma.
A Synthetic Nickel Electrocatalyst with a Turnover Frequency Above 100,000 s −1 for H 2 Production (2011)

Reduction of acids to molecular hydrogen as a means of storing energy is catalyzed by platinum, but its low abundance and high cost are problematic. Precisely controlled delivery of protons is critical in hydrogenase enzymes in nature that catalyze hydrogen (H(2)) production using earth-abundant metals (iron and nickel). Here, we report that a synthetic nickel complex, [Ni(P(Ph)(2)N(Ph))(2)](BF(4))(2), (P(Ph)(2)N(Ph) = 1,3,6-triphenyl-1-aza-3,6-diphosphacycloheptane), catalyzes the production of H(2) using protonated dimethylformamide as the proton source, with turnover frequencies of 33,000 per second (s(-1)) in dry acetonitrile and 106,000 s(-1) in the presence of 1.2 M of water, at a potential of -1.13 volt (versus the ferrocenium/ferrocene couple). The mechanistic implications of these remarkably fast catalysts point to a key role of pendant amines that function as proton relays.
DESIGN DOLDRUMS: SWATH & SEA KNIFE (1988)

According to the author, the Sea Knife triangular waterplane small craft and the small waterplane-area twin hull (SWATH) are two advanced hull forms with severe limitations as regards their suitability for certain U.S. Navy missions. Like all high- performance ships, they have a narrow band of optimum performance and are less able than conventional ships to adapt and continue to perform when operating outside their optimum. The specific attributes of the Sea Knife and SWATH hull forms, including their seakeeping qualities, are enumerated, and these are measured against Navy requirements for high-performance ships and special missions.
Construction and characterization of new cloning vehicles. II. A multipurpose cloning system. (1977)

In vitro recombination techniques were used to construct a new cloning vehicle, pBR322. This plasmid, derived from pBR313, is a relaxed replicating plasmid, does not produce and is sensitive to colicin E1, and carries resistance genes to the antibiotics ampicillin (Ap) and tetracycline (Tc). The antibiotic-resistant genes on pBR322 are not transposable. The vector pBR322 was constructed in order to have a plasmid with a single PstI site, located in the ampicillin-resistant gene (Apr), in addition to four unique restriction sites, EcoRI, HindIII, BamHI and SalI. Survival of Escherichia coli strain X1776 containing pBR313 and pBR322 as a function of thymine and diaminopimelic acid (DAP) starvation and sensitivity to bile salts was found to be equivalent to the non-plasmid containing strain. Conjugal transfer of these plasmids in bi- and triparental matings were significantly reduced or undetectable relative to the plasmid ColE1.
Poxvirus Cell Entry: How Many Proteins Does it Take? (2012)

For many viruses, one or two proteins enable cell binding, membrane fusion and entry. The large number of proteins employed by poxviruses is unprecedented and may be related to their ability to infect a wide range of cells. There are two main infectious forms of vaccinia virus, the prototype poxvirus: the mature virion (MV), which has a single membrane, and the extracellular enveloped virion (EV), which has an additional outer membrane that is disrupted prior to fusion. Four viral proteins associated with the MV membrane facilitate attachment by binding to glycosaminoglycans or laminin on the cell surface, whereas EV attachment proteins have not yet been identified. Entry can occur at the plasma membrane or in acidified endosomes following macropinocytosis and involves actin dynamics and cell signaling. Regardless of the pathway or whether the MV or EV mediates infection, fusion is dependent on 11 to 12 non-glycosylated, transmembrane proteins ranging in size from 4- to 43-kDa that are associated in a complex. These proteins are conserved in poxviruses making it likely that a common entry mechanism exists. Biochemical studies support a two-step process in which lipid mixing of viral and cellular membranes is followed by pore expansion and core penetration.
The discovery and clinical development of RPR 106541: an airway-selective steroid for the treatment of asthma (2000)

RPR 106541 (Rhône-Poulenc Rorer), a potential inhaled anti-asthmatic steroid, was developed in an environment which recognised the central role of glucocorticoids in the treatment of airway inflammation, but perceived the need to improve upon the tolerance profile of existing drugs. Preclinical candidate selection was based upon a screening program in which potential NMEs were tested alongside known drugs in tests of efficacy and safety. The subsequent clinical program targeted early (Phase I) assessments of performance against plasma and urine markers of tolerance and a surrogate end point of efficacy. Data from each of the above phases are presented and the value of the overall strategy is assessed against clinical outcomes in Phase IIa.
Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice. (1978)

Dendrite cells (DCs) are a new cell type initially identified in mouse lymphoid organs. Recently, DCs have been purified from mouse spleen. This paper demonstrates a functional role of DCs: they are potent stimulators of the primary mixed leukocytes reaction (MLR). As few as 300-1000 DCs doubled the proliferative activity of 5 X 10(6) allogeneic responder spleen cells, while 0.3-1.0 X 10(5) DCs induced a maximal stimulation of 30- to 80-fold. Between these extremes, the log of the MLR response increased linearly with the log of DC numbers. This dose-response assay was then used to compare the potency of purified DCs with that of other heterogeneous lymphoid populations, many of which gave dose-response curves with similar slopes. The potency of purified DCs as MLR stimulators was 100-300 times greater than that of unfractionated spleen cells. When spleen cells were fractionated by simple physical techniques, MLR-stimulating capacity in the subpopulations correlated closely with DC numbers. Removal of splenic B or T lymphocytes, by anti-immunoglobulin or anti-brain serum plus complement, did not reduce MLR-stimulating capacity. Finally, several populations, enriched in mononuclear phagocytes but lacking in DCs, stimulated weakly if at all. We conclude that DCs are a potent stimulating cell and are at least 100 times more effective than other major cell subclasses--i.e., B and T lymphocytes and macrophages.
Pharmacokinetics in Drug Discovery and Development (2002)

Pharmacokinetics has evolved from its origin into a complex discipline with numerous subspecialties and applications in patient management, drug development, and regulatory issues. This expansion has made it difficult for any one individual to become a full-fledged expert in all areas. Fulfilling the need for a wide-ranging guide to the many existi
An investigation of intracellular glycosylation activities in CHO cells: Effects of nucleotide sugar precursor feeding (2010)

Controlling glycosylation of recombinant proteins produced by CHO cells is highly desired as it can be directed towards maintaining or increasing product quality. To further our understanding of the different factors influencing glycosylation, a glycosylation sub-array of 79 genes and a capillary electrophoresis method which simultaneously analyzes 12 nucleotides and 7 nucleotide sugars; were used to generate intracellular N-glycosylation profiles. Specifically, the effects of nucleotide sugar precursor feeding on intracellular glycosylation activities were analyzed in CHO cells producing recombinant human interferon-gamma (IFN-gamma). Galactose (+/-uridine), glucosamine (+/-uridine), and N-acetylmannosamine (ManNAc) (+/-cytidine) feeding resulted in 12%, 28%, and 32% increase in IFN-gamma sialylation as compared to the untreated control cultures. This could be directly attributed to increases in nucleotide sugar substrates, UDP-Hex ( approximately 20-fold), UDP-HexNAc (6- to 15-fold) and CMP-sialic acid (30- to 120-fold), respectively. Up-regulation of B4gal and St3gal could also have enhanced glycan addition onto the proteins, leading to more complete glycosylation (sialylation). Combined feeding of glucosamine + uridine and ManNAc + cytidine increased UDP-HexNAc and CMP-sialic acid by another two- to fourfold as compared to feeding sugar precursors alone. However, it did not lead to a synergistic increase in IFN-gamma sialylation. Other factors such as glycosyltransferase or glycan substrate levels could have become limiting. In addition, uridine feeding increased the levels of uridine- and cytidine-activated nucleotide sugars simultaneously, which could imply that uridine is one of the limiting substrates for nucleotide sugar synthesis in the study. Hence, the characterization of intracellular glycosylation activities has increased our understanding of how nucleotide sugar precursor feeding influence glycosylation of recombinant proteins produced in CHO cells. It has also led to the optimization of more effective strategies for manipulating glycan quality.
Characterization of K Currents in Cultured Human Corporal Smooth Muscle Cells (1993)

In order to gain more mechanistic insight into the regulation of corporal smooth muscle tone, we conducted electrophysiological studies on homogeneous explant cell cultures of human corpus cavernosum smooth muscle. Patch clamp analyses in the whole cell mode revealed a mean resting potential of -43 +/- 4.9 m V (n = 12 cells). Large whole cell outward K currents were very prominent in these cells, and ranged from 0.5 to 1.5 nA. In some cells, a transient, voltage-dependent A current accounted for a significant portion of the observed whole cell currents. Furthermore, stimulation with the calcium channel agonist BAY K 8644 or the K channel agonist pinacidil doubled the magnitude of the whole cell K current, as would be expected for maxi-K (KCa) and metabolically gated K channels (KATP), respectively. Single channel recordings in the detached patch mode consistently revealed the presence of at least two K channels: 1) a KCa channel, with a conductance of approximately 190 pS; and 2) a putative delayed rectifier channel with a conductance of approximately 50 pS. Furthermore, all channel types showed some degree of voltage and/or calcium sensitivity. In conclusion, the large magnitude of the whole cell K currents and the observed K channel heterogeneity indicate a potentially important role for these channels in modulating corporal smooth muscle tone.
Interstitial wires releasing diffusing alpha emitters combined with chemotherapy improved local tumor control and survival in squamous cell carcinoma‐bearing mice (2009)

Antitumor activity and overall survival of metastatic tumor-bearing mice were improved significantly by the combined treatment. These results highlight the potential benefit of alpha radiation-based radiotherapy in combination with chemotherapeutic drugs for anticancer treatment.
Peptoid-Peptide Hybrids That Bind Syk SH2 Domains Involved in Signal Transduction (2001)

Peptoid-peptide hybrids are oligomeric peptidomimetics that contain one or more N-substituted glycine residues. In these hybrids, the side chains of one or several amino acids are "shifted" from the alpha-carbon atom to the amide nitrogen atom. A library of phosphorylated peptoid-peptide hybrids derived from the sequence pTyr-Glu-Thr-Leu was synthesized and tested for binding to the tandem SH2 domain of the protein tyrosine kinase Syk. A considerable influence of the side chain position was observed. Compounds 19-21, 24, and 25 comprising a peptoid NpTyr and/or NGlu residue did not show any binding. Compounds 22, 23, and 26 containing an NhThr (hThr=homothreonine) and/or NLeu peptoid residue showed binding with IC(50) values that were only five to eight times higher than that of the tetrapeptide lead compound 18. These data show that side chain shifting is possible with retention of binding capacity, but only at the two C-terminal residues of the tetramer. This method of a peptoid scan using peptoid-peptide hybrids appears to be very useful to explore to what extent a peptide sequence can be transformed into a peptoid while retaining its affinity.
Antioxidants for prevention of atrial fibrillation: a potentially useful future therapeutic approach? A review of the literature and meta-analysis (2014)

Atrial fibrillation (AF) is a self-perpetuating arrhythmia which is dependent upon structural and functional changes elicited by atrial high rate activity. Shortening of atrial effective refractory period is the earliest functional change which characterizes atrial remodelling. Studies in humans demonstrated oxidant species overproduction in the cardiac specimens from patients with AF and a significant association between reactive oxidant species (ROS) formation and risk of AF. Also, there is experimental evidence to suggest that ROS may be implicated not only in promoting AF but also in maintaining atrial arrhythmia. Several enzymatic pathways seem to be implicated in ROS overproduction, which ultimately leads to enhanced vulnerability to AF; they include myeloperoxidase, Nicotinamide adenine dinucleotide phosphate oxidase, and uncoupled nitric oxide synthase enzymes. To explore if ROS are implicated in promoting AF experimental studies with antioxidants, prevalently antioxidant vitamins such as ascorbic acid and vitamin E, have been planned. Furthermore, interventional trials have been carried out with antioxidants in clinical settings characterized by enhanced risk of AF. This review reports on experimental and clinical studies exploring the role of ROS in eliciting the occurrence or recurrence of AF and the potential efficacy of a treatment by antioxidant vitamins; furthermore, we performed a meta-analysis of the interventional trials in patients at risk of AF to see if antioxidant treatment is able to reduce the AF occurrence.
Comparison of Linear Statistical Methods for Calibration of NIR Instruments (1986)

T. Naes, C. Irgens, H. Martens, Comparison of Linear Statistical Methods for Calibration of NIR Instruments, Journal of the Royal Statistical Society. Series C (Applied Statistics), Vol. 35, No. 2 (1986), pp. 195-206
Poly(p-phenylene ethynylene) Brushes (2002)

ADVERTISEMENT RETURN TO ISSUEPREVCommunication to the...Communication to the EditorNEXTPoly(p-phenylene ethynylene) BrushesJoong Ho Moon and Timothy M. SwagerView Author Information Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Cite this: Macromolecules 2002, 35, 16, 6086–6089Publication Date (Web):June 29, 2002Publication History Received29 April 2002Revised6 June 2002Published online29 June 2002Published inissue 1 July 2002https://pubs.acs.org/doi/10.1021/ma025539rhttps://doi.org/10.1021/ma025539rrapid-communicationACS PublicationsCopyright © 2002 American Chemical SocietyRequest reuse permissionsArticle Views780Altmetric-Citations29LEARN 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:Catalysts,Polymer brushes,Polymer films,Polymers,Quantum yield Get e-Alerts
Biofeedback and Visceral Learning (1978)

In instrumental learning (also called trial-and-error learning or operant condition­ ing), whether a response is learned and performed depends on whether that response is followed by a reward or by a punishment. When a novice is learning better voluntary control over where the ball goes in shooting fouls, seeing the ball go through the hoop (success) serves as a reward, and seeing it miss (failure) serves as a punishment. If a novice were blindfolded so that he did not have any knowledge of the results of his shots, he would not learn. Rewards, punishments, and knowl­ edge of results have been called feedback. Most people are poor at correctly perceiving their visceral responses, such as blood pressure, and some people with tension or neuromuscular disorders are poor at perceiving feedback from certain skeletal muscles. They are like a blindfolded novice trying to learn to shoot baskets. Modern measuring devices can remove the blindfold by supplying better feedback. Feedback provided by a device that provides prompt measurement of a biological function has been called biofeedback. It should be useful for any learnable response the acquisition of which is impeded by poor or erroneous perception of the correct response (137). Biofeedback can be used also to help animals and people to learn to improve the perception of certain visceral events (1). Such learned perception in patients sometimes can eliminate the need for assistance from the biofeedback instrument (138). An attractive feature of biofeed­ back is that it teaches the patient to do something for himself. Biofeedback is part of a larger new area of research called behavioral medicine. Previously, behavioral science has been related primarily to one branch of medicine, psychiatry; now it is becoming related to the rest of medicine (140, 147,210). One of the important areas of behavioral medicine is the effects of stress on psy­ chosomatic symptoms, on the immune system, and on a wide range of diseases and disorders (141). By emphasizing the measurement of and the production of changes in bodily processes, biofeedback is contributing to the applications to medicine of other behavioral techniques for relief from stress, such as transcendental meditation
Relief of Pain by Anterior Cervical-Spine Fusion for Spondylosis (1973)

An extensive evaluation of the results of anterior spine fusion in sixty-five patients with cervical spondylosis showed that good results with respect to relief of pain were Obtained in 90 per cent. The factors predisposing to more favorable results were: presence of radicular symptoms preoperatively, presence of positive roentgenographic findings at only one vertebral level, presence of myelographic defects which correlated with the levels operated on, and achievement of a solid union without interspace collapse. None of these factors, however, were indispensable to a good result. Those factors which were associated with a bad result were: the presence preoperatively of long tract signs and the preoperative presence of subluxation of a vertebra. Psychological testing (Cornell Index) did not differentiate whether the results would be favorable or unfavorable.
MODULUS AND THICKNESS OF THE PAVEMENT SURFACE LAYER FROM SASW TESTS (1990)

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Activating transcription factor-1 can mediate Ca(2+)- and cAMP-inducible transcriptional activation. (1993)

Increased intracellular cAMP and Ca2+ levels can activate transcription of a number of eukaryotic genes through a common promoter element, the cAMP/Ca2+ response element. This element is the binding site for activating transcription factor (ATF)/CREB proteins, an extensive transcription factor family. Here we report that one member of this family, ATF-1, can mediate both Ca2+ and cAMP transcriptional responses, but that the responses to the two pathways differ in magnitude. In contrast, another family member, CREB, has been shown to mediate Ca2+ and cAMP responses to similar levels. Taken together, these results suggest a mechanism that allows cells to integrate and differentiate gene regulation by cAMP and Ca2+.
Abnormal wound healing responses in pulmonary fibrosis: focus on coagulation signalling (2008)

The normal response of tissue to injury involves a sequence of overlapping events, which need to occur in a timely and controlled manner for successful tissue repair and restoration of normal function. Failure to control the healing process can lead to considerable tissue remodelling and the replacement of functional tissue with permanent fibrous scar tissue. It is proposed that pulmonary fibrosis arises from repetitive, widespread epithelial injury. However, the nature of the insult for the most common and most fatal form of pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF), is currently unknown and the pathogenetic pathways leading to IPF remain to be fully elucidated. Increasing evidence suggests that abnormalities in a number of pathways involved in the wound healing response may play central roles. The present article will briefly review the pathways involved in wound healing focusing on the control of fibroblast/myofibroblast function and the coagulation cascade acting via the family of signalling receptors, the proteinase activated receptors, which influence a range of cellular responses implicated in the development of pulmonary fibrosis. Understanding the involvement of these pathways in the aberrant wound repair-response in pulmonary fibrosis may lead to the identification of new targets and strategies for therapeutic intervention.