gebhart/patrepeval huggingface dataset:
Antimicrobial stewardship in wound care: a Position Paper from the British Society for Antimicrobial Chemotherapy and European Wound Management Association (2016)

Available evidence is limited, but suggests that applying principles of AMS to the care of patients with wounds should help to reduce the unnecessary use of systemic or topical antibiotic therapy and ensure the safest and most clinically effective therapy for infected wounds.
Magnetic endotracheal tube imaging device (2008)

This paper describes an accurate, economical, and portable device that helps to locate the position of an endotracheal tube (ETT) in situ. The device uses an array of magnetic field sensors to detect an anomaly in magnetic field caused by magnet embedded near the cuff of an ETT, and displays an intuitive map of relative magnetic field intensity under the sensor area. The device provides real-time feedback of the position to a clinician, so that corrective measures can be taken if the ETT is determined to be outside of normal positioning with respect to the patient's airway. Variations of the proposed design are suitable for continuous monitoring.
Up-regulation of Microglial CD11b Expression by Nitric Oxide (2006)

Increased expression of CD11b, the beta-integrin marker of microglia, represents microglial activation during neurodegenerative inflammation. However, the molecular mechanism behind increased microglial CD11b expression is poorly understood. The present study was undertaken to explore the role of nitric oxide (NO) in the expression of CD11b in microglial cells. Bacterial lipopolysaccharide (LPS) induced the production of NO and increased the expression of CD11b in mouse BV-2 microglial cells and primary microglia. Either a scavenger of NO (PTIO) or an inhibitor of inducible nitric-oxide synthase (L-NIL) blocked this increase in microglial CD11b expression. Furthermore, co-microinjection of PTIO with LPS was also able to suppress LPS-mediated expression of CD11b and loss of dopaminergic neuronal fibers and neurotransmitters in striatum in vivo. Similarly, other inducers of NO production such as interferon-gamma, interleukin-1beta, human immunodeficiency virus type-1 gp120, and double-stranded RNA (poly(IC)) also increased the expression of CD11b in microglia through NO. The role of NO in the expression of CD11b was corroborated further by the expression of microglial CD11b by GSNO, an NO donor. Because NO transduces many intracellular signals via guanylate cyclase (GC), we investigated the role of GC, cyclic GMP (cGMP), and cGMP-activated protein kinase (PKG) in microglial expression of CD11b. Inhibition of LPS- and GSNO-mediated up-regulation of CD11b either by NS2028 (a specific inhibitor of GC) or by KT5823 and Rp-8-bromo-cGMP (specific inhibitors of PKG), and increase in CD11b expression either by 8-bromo-cGMP or by MY-5445 (a specific inhibitor of cGMP phosphodiesterase) alone suggest that NO increases microglial expression of CD11b via GC-cGMP-PKG. In addition, GSNO induced the activation of cAMP response element-binding protein (CREB) via PKG that was involved in the up-regulation of CD11b. This study illustrates a novel biological role of NO in regulating the expression of CD11b in microglia through GC-cGMP-PKG-CREB pathway that may participate in the pathogenesis of devastating neurodegenerative disorders.
In vitro myelosuppression of SJG-136, a pyrrolobenzodiazepine dimer: Comparison to bizelesin. (2004)

2113 The pyrrolobenzodiazepine dimer SJG-136 (NSC-694501) is an anthramycin-like compound that is a potent sequence-selective DNA minor groove cross-linking agent. SJG-136 is similar to bizelesin, another potent DNA minor groove alkylating agent, in that both agents cause dose-limiting myelosuppression. In vitro, bizelesin was previously shown to be much more toxic to human and canine granulocyte-macrophage colony-forming units (CFU-GM) than to murine CFU-GM (the IC90’s were 660 nM, 2659 pM, and 906 pM for murine, canine, and human cells, respectively). Clinically, an effective dose of bizelesin was not reached due to dose-limiting myelosuppression. To determine if this large species disparity also exists for SJG-136, in vitro bone marrow assays were conducted prior to embarking on animal toxicity studies. Murine, canine, and human CFU-GM were exposed continuously to SJG-136 for 7-10 days at concentrations of 0.001-10 nM. The number of surviving CFU-GM was determined and the IC90 was calculated for each species. Murine cells were 3.2-fold less sensitive and canine cells were 1.8-fold more sensitive than human cells, respectively (IC90’s for murine, canine, and human cells were 2640, 442 and 826 pM). The large disparity in species sensitivity that was noted with bizelesin therefore does not occur with SJG-136. Based on these in vitro bone marrow data, the projected maximum tolerated dose (MTD) of SJG-136 in humans is 37-115 μg/m2/day (i.e. between 1.8 times the in vivo dog MTD of 20 μg/m2/day, and 3.2-fold less than the in vivo mouse MTD of 366 μg/m2/day). Since the human MTD falls between the in vivo mouse minimal effective dose (48 ug/m2/day) and the mouse MTD (366 μg/m2/day), clinically effective doses of SJG-136 should be attainable at doses that do not cause dose-limiting myelosuppression.
VLSI design of inverse-free Berlekamp—Massey algorithm (1991)

The Berlekamp-Massey algorithm for decoding BCH codes is modified to eliminate the calculation of inverses. This new algorithm is useful in the practical application of multiple-error-correcting BCH or RS codes. A VLSI architecture is developed for this algorithm.
High-impedance electromagnetic surfaces with a forbidden frequency band (1999)

A new type of metallic electromagnetic structure has been developed that is characterized by having high surface impedance. Although it is made of continuous metal, and conducts dc currents, it does not conduct ac currents within a forbidden frequency band. Unlike normal conductors, this new surface does not support propagating surface waves, and its image currents are not phase reversed. The geometry is analogous to a corrugated metal surface in which the corrugations have been folded up into lumped-circuit elements, and distributed in a two-dimensional lattice. The surface can be described using solid-state band theory concepts, even though the periodicity is much less than the free-space wavelength. This unique material is applicable to a variety of electromagnetic problems, including new kinds of low-profile antennas.
Modification of Initial Highly Active Antiretroviral Therapy (HAART) Regimen in Paediatric HIV Patients (2018)

Poor adherence was significantly associated with initial regimen modification, intervention to improve patient's adherence is necessary to prevent multiple regimen modification among HIV-infected children.
Oral health knowledge, attitude and behaviour of 12-year-old suburban and rural school children in Nigeria. (1994)

The aim of the study was to investigate the oral health knowledge, attitudes and behaviour of 12-year-old primary school children living in suburban and rural Nigeria. A total of 574 children mostly from low socioeconomic status were studied through questionnaires. Relatively high level of oral health knowledge and positive attitudes to prevention were found. Majority of suburban children (72.5%) cleaned their teeth with toothbrush and toothpaste while most of the rural dwellers (49.8%) used chewing sticks. Overall, 83.5 per cent of all the children had never visited the dentist despite the fact that most of them believed it was necessary to visit the dentist for check-up. It was concluded that oral health education programme should be targeted to the need of the communities.
Muscarinic receptor binding, plasma concentration and inhibition of salivation after oral administration of a novel antimuscarinic agent, solifenacin succinate in mice (2005)

1 A novel muscarinic receptor antagonist, solifenacin succinate, inhibited specific binding of [N-methyl-(3)H]-scopolamine ([(3)H]-NMS) in the mouse bladder, submaxillary gland and heart in a concentration-dependent manner. This inhibitory effect was greatest in the submaxillary gland, followed by the bladder and heart. 2 After oral administration of oxybutynin (76.1 micromol kg(-1)) or solifenacin (62.4, 208 micromol kg(-1)), a significant dose- and time-dependent increase in K(D) values for specific [(3)H]-NMS binding was seen in the bladder, prostate, submaxillary gland, heart, colon and lung, compared with control values. The increase in K(D) induced by oxybutynin in each tissue reached a maximum 0.5 h after oral administration and then rapidly declined, while that induced by solifenacin was greatest 2 h after administration and was maintained for at least 6 or 12 h, depending on the dose. The muscarinic receptor binding of oral solifenacin was slower in onset and of a longer duration than that of oxybutynin. 3 Plasma concentrations of oxybutynin and its active metabolite (N-desethyl-oxybutynin, DEOB) were maximum 0.5 h after its oral administration and then declined rapidly. Oral solifenacin persisted in the blood for longer than oxybutynin. 4 Pilocarpine-induced salivary secretion in mice was significantly reduced by oral administration of solifenacin and was completely abolished 0.5 h after oral oxybutynin. Although the suppression induced by solifenacin was more persistent than that due to oxybutynin, the antagonistic effect of solifenacin on the dose-response curves to pilocarpine was significantly weaker than that of oxybutynin. It is concluded that oral solifenacin persistently binds to muscarinic receptors in tissues expressing the M(3) subtype, such as the bladder.
Power Substation Automation Using a Knowledge Based System - Justification and Preliminary Field Experiments (1987)

Conventional automation and control devices are passive and responsive. These devices typically "respond" to changes in the power system as measured against fixed thresholds and preset limits. These systems are designed to prevent catastrophic failures and incorrect operations and work well for general data acquisition and remote supervisory control. How ever, feedback control, system diagnostics, advanced protection, and contingency control are difficult to implement on the ever changing power system with these conventional approaches. Knowledge based systems have the potential for following the changes in the power system and adjusting decision criteria accordingly. Decisions can be made on a more complete data base which is constantly adjusted to changes ir system parameters and operation. This paper describes the various functions where knowledge based systems could ideally be used. The use of a knowledge based, adaptive system approach for diagnosing distribution system disturbances and equipment failures is presented. Two field experiments are described.
Discovery and Optimization of Allosteric Inhibitors of Mutant Isocitrate Dehydrogenase 1 (R132H IDH1) Displaying Activity in Human Acute Myeloid Leukemia Cells (2016)

A collaborative high throughput screen of 1.35 million compounds against mutant (R132H) isocitrate dehydrogenase IDH1 led to the identification of a novel series of inhibitors. Elucidation of the bound ligand crystal structure showed that the inhibitors exhibited a novel binding mode in a previously identified allosteric site of IDH1 (R132H). This information guided the optimization of the series yielding submicromolar enzyme inhibitors with promising cellular activity. Encouragingly, one compound from this series was found to induce myeloid differentiation in primary human IDH1 R132H AML cells in vitro.
Combination therapy with low-dose aspirin and ticlopidine in cerebral ischemia. (1989)

We compared combination therapy with low-dose aspirin plus ticlopidine to therapy with aspirin alone or ticlopidine alone in patients suffering transient ischemic attack or cerebral infarction. In 17, 24, and 23 patients, respectively, 300 mg/day aspirin, 200 mg/day ticlopidine, and 81 mg/day aspirin plus 100 mg/day ticlopidine were administered orally. Aspirin alone markedly inhibited platelet aggregation induced by arachidonic acid, partially inhibited platelet aggregation induced by adenosine diphosphate, and did not inhibit platelet aggregation induced by platelet activating factor. Ticlopidine alone inhibited platelet aggregation induced by adenosine diphosphate and platelet activating factor, but did not inhibit platelet aggregation induced by arachidonic acid. Combination therapy with aspirin plus ticlopidine markedly inhibited platelet aggregation induced by all three agonists. Plasma concentrations of beta-thromboglobulin and platelet factor 4 remained unchanged by aspirin alone, were slightly reduced by ticlopidine alone, and were markedly reduced by aspirin plus ticlopidine. Plasma concentration of thromboxane B2 was reduced by aspirin alone or with ticlopidine, but not by ticlopidine alone. The level of 6-ketoprostaglandin F1 alpha was reduced only by aspirin alone. Bleeding time was significantly prolonged by aspirin alone and by ticlopidine alone, although the greatest prolongation was produced by aspirin plus ticlopidine. Our results indicate that the combination of aspirin plus ticlopidine is a potent antiplatelet strategy, although the clinical importance of the changes observed need to be determined by a properly designed and controlled prospective study.
Identification of an active site on the laminin α4 chain globular domain that binds to αvβ3 integrin and promotes angiogenesis (2006)

Angiogenesis is important for wound healing, tumor growth, and metastasis. The laminin alpha4 chain, a component of laminin-8 and -9, is expressed in endothelial cell basement membranes. It mediates endothelial cell adhesion by binding with its receptors such as alphavbeta3 integrin and participates in new blood vessel formation. In this study, we found the recombinant laminin alpha4LG modules (rLG1-3, rLG1, and rLG2) mediate HUVECs adhesion. The attachment of HUVECs to the rLG2 was specifically inhibited by a function-blocking monoclonal antibody LM609 specific for alphavbeta3 integrin. Using deletion mutants of the alpha4LG2 revealed the HUVECs-adhesion site is located in amino acids 1121-1139. A synthetic G(1121-1139) peptide could be attached by HUVECs at same efficiency with the rLG2 and promoted angiogenesis in CAM. In conclusion, we have identified a new alphavbeta3 integrin-interacting peptide within laminin alpha4 G domain. This suggests that G(1121-1139) peptide-containing proteins may perform their biological functions by interacting with alphavbeta3 integrin.
MEDIATORS OF INFLAMMATION IN LEUKOCYTE LYSOSOMES (1968)

The present study demonstrates that a granule fraction derived from human polymorphonuclear leukocytes possesses elastinolytic activity, and that the latter can be separated from the collagenase present in these cells. Properties of the human leukocyte elastase differ sufficiently from those of pancreatic elastases of different species as to suggest that the former enzyme is a distinct and separate entity. Thus, soybean trypsin inhibitor and salivary kallikrein inhibitor (Trasylol) fail to inhibit elastolysis by the pancreatic enzyme, but do inhibit the leukocyte elastinolytic agent. Elastolysis by human leukocyte granule extract does not show significant salt inhibition, whereas that catalyzed by pancreatic elastase is markedly reduced when ionic strength is increased to physiological levels. The leukocyte granule extract is at least 10 times more resistant to serum elastase inhibitor than is the purified pancreatic enzyme. Both enzymes show optimal elastolysis above pH 8.5, but the leukocyte factor still retains 50% of its maximal elastolytic activity at pH 6-7; whereas the activity of the pancreatic enzyme falls to 10% or less of its maximal value under the same conditions. The foregoing characteristics of the human leukocyte elastase suggest that it, rather than pancreatic (serum) elastase, may mediate pathological elastolysis during acute arteritis in man. In keeping with this suggestion, the present experiments also show that elastica staining of human arterial vessels is reduced by incubation of tissues with human leukocyte granule extracts in vitro.
Strong inhibition of fibrinogen binding to platelet receptor αIIbβ3 by RGD sequences installed into a presentation scaffold (1993)

In order to probe the structural constraints on binding of RGD sequences to the platelet receptor alpha IIb beta 3 we have used recombinant DNA techniques to install the RGD sequence into 'presentation scaffolds', small proteins of known 3-D structure chosen to present guest sequences in constrained orientations. Using Escherichia coli expression systems we made sequence variants in which loop residues of the immunoglobulin VL domain REI and of human interleukin-1 beta were replaced (without changing polypeptide length) by the RGD sequence at positions predicted, based on small molecule studies, to orient the RGD moiety into an active conformation. These variants do not compete for fibrinogen binding to alpha IIb beta 3 up to almost 1 mM concentration. Unfolded or proteolytically fragmented forms of these same proteins do compete, however, showing that the RGD sequences in the mutants must be prohibited from binding by constraints imposed by scaffold structure. To suppress the effects of such structural constraints we constructed two sequence variants in which RGD-containing sequences 42-57 or 44-55 from the snake venom platelet antagonist kistrin were inserted (this increasing the length of the loop) into the third complementarity determining loop of REI. Both of these variants compete strongly for fibrinogen binding with IC50s in the nM range. These results, plus data on kistrin-related peptides also presented here, suggest that the molecular scaffold REI is capable of providing to an installed sequence a structural context and conformation beneficial to binding. The results also suggest that in order to bind well to alpha IIb beta 3, RGD sequences in protein ligands must either project significantly from the surface of the scaffold and/or retain a degree of conformational flexibility within the scaffold. Molecular scaffolds like REI should prove useful in the elucidation of structure-function relationships and the discovery of new active sequences, and may also serve as the basis for novel therapeutic agents.
Influence of the Genotype on the Clinical Course of the Long-QT Syndrome (1998)

The genotype of the long-QT syndrome influences the clinical course. The risk of cardiac events is significantly higher among subjects with mutations at the LQT1 or LQT2 locus than among those with mutations at the LQT3 locus. Although cumulative mortality is similar regardless of the genotype, the percentage of cardiac events that are lethal is significantly higher in families with mutations at the LQT3 locus.
Activin modulates the intracellular signaling system activated by gonadotropin-releasing hormone: dual effect on calcium messenger system and protein kinase-C pathway. (1994)

This study was performed to assess the effects of activin on intracellular mechanisms involved in GnRH action. When rat pituitary cell cultures were pretreated with activin-A (5-80 ng/ml) for 3 days, subsequent FSH and LH release (percentage of total cellular FSH and LH released during 4 h) in response to GnRH (10(-10)-10(-6) M) was not significantly different from that in cells pretreated with medium alone. In contrast, activin pretreatment increased the potency of both A23187 (Ca2+ ionophore) and phorbol 12-myristate 13-acetate [a protein kinase-C (PKC) activator] as secretagogues for FSH and LH release. FSH or LH release in response to another Ca(2+)-mobilizing secretagogue, maitotoxin (an activator of the GnRH receptor-associated Ca2+ channel), was not increased by activin. Although PKC is capable of influencing the actions of Ca2+, which is believed to be the second messenger for GnRH action, neither GnRH- nor maitotoxin-stimulated gonadotropin release was increased by activin even when the influence of activin on PKC was eliminated by the addition of a PKC inhibitor (staurosporine; 100 nM) during the final 30 min of the 3-day pretreatment period. These results indicate that although activin does not influence GnRH action with regard to gonadotropin release, it increases the sensitivity of the system regulating gonadotropin release to increases in cytosolic Ca2+ concentrations and PKC activation. Furthermore, activin appears to exhibit an inhibitory effect(s) at some point(s) in GnRH action in a PKC-independent manner, which could be responsible for opposing the increased sensitivity of the gonadotrope to Ca2+. The differential effects of activin on gonadotropin release in response to Ca(2+)-mobilizing secretagogues (ionophore and maitotoxin) raise the possibility that the activity of the GnRH receptor-associated Ca2+ channel may be suppressed by activin.
Superior Therapeutic Efficacy of Alphavirus-Mediated Immunization against Human Papilloma Virus Type 16 Antigens in a Murine Tumour Model: Effects of the Route of Immunization (2004)

In our efforts to develop a strong, effective immune response against cervical carcinoma and premalignant disease, we study the use of recombinant Semliki Forest virus (SFV) encoding the oncoproteins E6 and E7 from high-risk human papilloma viruses (HPVs). Optimal immunization conditions are required for immunotherapeutic treatment of cervical cancer as it has been postulated that cervical cancer patients are immune-suppressed and/or immunologically tolerant for HPV. We previously generated an optimized construct encoding a fusion protein of HPV16 E6 and E7 and a translational enhancer (enhE6,7). Immunization of mice with SFV-enhE6,7 was shown to induce cytoxic T cell (CTL) responses and resulted in the eradication of established tumours. We now demonstrate, using HPV16-specific MHC class I tetramers, that high pCTL frequencies can be induced. However, this induction is strongly influenced by the route of immunization applied. Whilst in bulk CTL assays, requiring in vitro restimulation, CTL activity can be observed upon s.c., i.p., i.v. and i.m. immunization, detectable pCTL frequencies, without in vitro restimulation, are only induced upon i.m. and i.v. immunization. The route of immunization also strongly influences the dose of viral vector needed to induce CTLs and tumour therapy. As few as 5x10(4) SFV-enhE6,7, primed and boosted i.v., are needed to eradicate tumours in six out of seven mice treated. Furthermore, exponentially growing tumours of approximately 500 mm3 in size were seen to completely resolve and even tumours as large as 1500 mm3 decreased to one-third of their size. Apart from this potency, SFV vectors can safely be used for the expression of oncoproteins such as E6 and E7, since the viral RNA is not integrated in the host genome. Thus SFV-enhE6,7 meets with the criteria that a vaccine against cervical cancer should be safe and induce a very strong, long-lasting CTL response, strong enough to eradicate existing tumours.