gebhart/patrepeval huggingface dataset:
A clinical microwave hyperthermia system with multipoint real-time thermal dosimetry (1985)

A clinical hyperthermia system using a 915 MHz microwave generator and incorporating multipoint thermocouple thermometry is described. Temperatures can be monitored simultaneously at 16 points and measurements displayed on a visual display unit and a plotter. The power output of the generator is adjusted under computer control to maintain a constant predetermined temperature in a chosen control channel. A clinically useful feature of the system is the ability to determine the effective cumulative thermal dose delivered to the tissue at points monitored in real time. The basis for the thermal dose calculation is discussed in detail. The calculated dose parameter is displayed for each of the 16 channels during the treatment and updated every 30 s. This real-time display of a thermal dose parameter has made possible a more homogeneous heating of tumours.
A COMPARISON OF TRIMETHOPRIM-SULPHAMETHOXAZOLE WITH OXYTETRACYCLINE IN ACNE VULGARIS (1971)

Journal Article A COMPARISON OF TRIMETHOPRIM‐SULPHAMETHOXAZOLE WITH OXYTETRACYCLINE IN ACNE VULGARIS Get access J. A. COTTERILL, J. A. COTTERILL Department of Dermatology, The General Infirmary at Leeds Search for other works by this author on: Oxford Academic Google Scholar W. J. CUNLIFFE, W. J. CUNLIFFE Department of Dermatology, The General Infirmary at Leeds Search for other works by this author on: Oxford Academic Google Scholar R. A. FORSTER, R. A. FORSTER Department of Dermatology, The General Infirmary at Leeds Search for other works by this author on: Oxford Academic Google Scholar D. M. WILLIAMSON, D. M. WILLIAMSON Departments of Pontefract General Infirmary, Mineral Metabolism Unit, The General Infirmary at Leeds Search for other works by this author on: Oxford Academic Google Scholar L. BULUSU L. BULUSU Medical Research Council, Mineral Metabolism Unit, The General Infirmary at Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 84, Issue 4, 1 April 1971, Pages 366–369, https://doi.org/10.1111/j.1365-2133.1971.tb14233.x Published: 01 April 1971 Article history Accepted: 09 December 1970 Published: 01 April 1971
Regulation of Malonyl-CoA Metabolism by Acyl-Acyl Carrier Protein and β-Ketoacyl-Acyl Carrier Protein Synthases in Escherichia coli (1995)

The cessation of phospholipid biosynthesis by the inhibition of the sn-glycerol-3-phosphate acyltransferase using a plsB mutant led to an accumulation of long chain acyl-acyl carrier proteins (acyl-ACP) and the concomitant inhibition of de novo fatty acid biosynthesis in Escherichia coli. Malonyl-CoA did not accumulate when phospholipid and fatty acid synthesis was blocked. However, the inactivation of beta-ketoacyl-ACP synthases I and II with the antibiotic cerulenin triggered a large increase in the accumulation of malonyl-CoA following the cessation of phospholipid synthesis, illustrating that the beta-ketoacyl-ACP synthases were responsible for the degradation of malonyl-CoA in the presence of long chain acyl-ACP. The acyl-ACP requirement for malonyl-CoA degradation activity was confirmed by shifting enoyl-ACP reductase mutants (fabI(Ts)) to the non-permissive temperature, leading to the abrupt cessation of fatty acid synthesis and the accumulation of malonyl-CoA in the absence of cerulenin. Analysis of the ACP pool composition before and after the temperature shift showed that the fabI block did not result in the accumulation of long chain acyl-ACP. These data indicate a feedback regulatory loop that functions to recycle malonyl-CoA to acetyl-CoA following the down-regulation of fatty acid and phospholipid formation and provides a physiological rationale for the acyl-ACP-dependent, malonyl-ACP decarboxylase reaction catalyzed by beta-ketoacyl-ACP synthases I and II.
Efficient Extraction of Virus DNA by NucliSens Extractor Allows Sensitive Detection of Hepatitis B Virus by PCR (2001)

The NucliSens Extractor is an automated nucleic acid isolation system based on guanidinium thiocyanate (GuSCN)-silica extraction technology. The system has been validated for the isolation of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) RNAs from human samples in combination with nucleic acid sequence-based amplification- and reverse transcription-PCR-based methods. We evaluated the extractor for hepatitis B virus (HBV) DNA extraction from human samples using a noncommercial HBV DNA PCR. Several sample pretreatment procedures in combination with the extractor were compared with the Qiagen extraction method, and the impact of the sample volume used in the extraction on the sensitivity was investigated. Heating of the lysed sample prior to extractor isolation and the use of a large sample volume resulted in highly sensitive detection of HBV DNA. Incubation of a 1-ml sample in GuSCN at 80 degrees C (10 min) and at 37 degrees C (30 min) allowed detection of 4 and 40 HBV genome equivalents/ml, respectively, in standard dilution panels. Sample lysis in GuSCN at room temperature and proteinase K treatment prior to use of the extractor were less efficient procedures. All clinical samples that were PCR positive after Qiagen extraction and/or that were HBsAg positive were also PCR positive after extractor isolation. HBV DNA, HCV RNA, and HIV type 1 RNA were efficiently coextracted from a single sample, allowing reliable detection of viral genomes.
Synergistic induction of promoters containing metal- and glucocorticoid-responsive elements (1992)

We have shown that it is possible to synergistically activate gene transcription when several glucocorticoid responsive elements (GREs) and metal responsive elements (MREs) that coexist within the same promoter are induced simultaneously. To demonstrate this, additional GREs were introduced into a human metallothionein IIA (hMT-IIA) promoter in which some constitutive elements had been deleted. The transcriptional strength and inducibility of the modified hMT-IIA promoters were studied in transient expression experiments using the CAT gene as a reporter. As a result of synergistic activation of transcription by CdCl2 and dexamethasone, the induced expression levels of the modified promoters were significantly higher than those obtained with wild-type hMT-IIA. Since the increase in inducible expression was not accompanied by a concominant increase in basal levels, the inducibility of the modified MT promoters was up to 6-fold higher. The degree of transcriptional synergism was shown to depend on the position and the number of GREs introduced. Thus, the engineering of synthetic promoters that include both GREs and MREs should offer the opportunity to develop a new series of improved inducible mammalian expression vectors.
Erlotinib in Lung Cancer — Molecular and Clinical Predictors of Outcome (2005)

Among patients with non-small-cell lung cancer who receive erlotinib, the presence of an EGFR mutation may increase responsiveness to the agent, but it is not indicative of a survival benefit.
Investigation of Optical Coherence Microelastography as a Method to Visualize Cancers in Human Breast Tissue (2015)

An accurate intraoperative identification of malignant tissue is a challenge in the surgical management of breast cancer. Imaging techniques that help address this challenge could contribute to more complete and accurate tumor excision, and thereby help reduce the current high reexcision rates without resorting to the removal of excess healthy tissue. Optical coherence microelastography (OCME) is a three-dimensional, high-resolution imaging technique that is sensitive to microscale variations of the mechanical properties of tissue. As the tumor modifies the mechanical properties of breast tissue, OCME has the potential to identify, on the microscale, involved regions of fresh, unstained tissue. OCME is based on the use of optical coherence tomography (OCT) to measure tissue deformation in response to applied mechanical compression. In this feasibility study on 58 ex vivo samples from patients undergoing mastectomy or wide local excision, we demonstrate the performance of OCME as a means to visualize tissue microarchitecture in benign and malignant human breast tissues. Through a comparison with corresponding histology and OCT images, OCME is shown to enable ready visualization of features such as ducts, lobules, microcysts, blood vessels, and arterioles and to identify invasive tumor through distinctive patterns in OCME images, often with enhanced contrast compared with OCT. These results lay the foundation for future intraoperative studies. Cancer Res; 75(16); 3236-45. ©2015 AACR.
Paracrinology of islets and the paracrinopathy of diabetes (2010)

New results have brought to light the importance of the regulation of glucagon by β-cells in the development of diabetes. In this perspective, we examine the normal paracrinology of α- and β-cells in nondiabetic pancreatic islets. We propose a Sherringtonian model of coordinated reciprocal secretory responses of these juxtaposed cells that secrete glucagon and insulin, hormones with opposing actions on the liver. As insulin is a powerful inhibitor of glucagon, we propose that within-islet inhibition of α-cells by β-cells creates an insulin-to-glucagon ratio that maintains glycemic stability even in extremes of glucose influx or efflux. By contrast, in type 1 diabetes mellitus, α-cells lack constant action of high insulin levels from juxtaposed β-cells. Replacement with exogenous insulin does not approach paracrine levels of secreted insulin except with high doses that "overinsulinize" the peripheral insulin targets, thereby promoting glycemic volatility. Based on the stable normoglycemia of mice with type 1 diabetes during suppression of glucagon with leptin, we conclude that, in the absence of paracrine regulation of α-cells, tonic inhibition of α-cells improves the dysregulated glucose homeostasis. These results have considerable medical implications, as they suggest new approaches to normalize the extreme volatility of glycemia in diabetic patients.
Ligand Valency Affects Transcytosis, Recycling and Intracellular Trafficking Mediated by the Neonatal Fc Receptor (2006)

The neonatal Fc receptor (FcRn) transports IgG across epithelial cell barriers to provide maternal antibodies to offspring and serves as a protection receptor by rescuing endocytosed IgG and albumin from lysosomal degradation. Here we describe the generation of polarized Madin-Darby canine kidney (MDCK) cells expressing rat FcRn (rFcRn) to investigate the potential requirement for ligand bivalency in FcRn-mediated transport. The rFcRn-MDCK cells bind, internalize and bidirectionally transcytose the bivalent ligands IgG and Fc across polarized cell monolayers. However, they cannot be used to study FcRn-mediated transport of the monovalent ligand albumin, as we observe no specific binding, internalization or transcytosis of rat albumin. To address whether ligand bivalency is required for transport, the ability of rFcRn to transcytose and recycle wild-type Fc homodimers (wtFc; two FcRn-binding sites) and a heterodimeric Fc (hdFc; one FcRn-binding site) was compared. We show that ligand bivalency is not required for transcytosis or recycling, but that wtFc is transported more efficiently than hdFc, particularly at lower concentrations. We also demonstrate that hdFc and wtFc have different intracellular fates, with more hdFc than wtFc being trafficked to lysosomes and degraded, suggesting a role for avidity effects in FcRn-mediated IgG transport.
Evidence of a founder effect in families with frontotemporal dementia that harbor the tau +16 splice mutation (2003)

The +16 exon 10 splice mutation of the tau gene (microtubule-associated protein tau, MAPT) has been reported in numerous families with frontotemporal dementia (FTD). To date, the majority of these families are from England and Wales in the UK, although families with this mutation have been reported from Australia and the USA. Our own analysis has identified eight families with the +16 MAPT splice mutation from around the Manchester and North Wales areas of the UK. Given the proximity of the UK families to one another it is likely that they are related and represent a single extended pedigree. In order to investigate this possibility, and the possibility that the families with this mutation from London, the USA, and Australia are related, we genotyped 11 microsatellite markers around the tau locus. In most cases (20/25, 80%), a common haplotype, approximately 3 cM in size, was identified. In the remaining cases, this haplotype appears to have been varyingly reduced in size by recombination. We demonstrate that the +16 mutation is on the H1 tau haplotype and that H1 specific polymorphisms are also shared by these families. These data provide evidence that the MAPT +16 splice mutation cases from around the world analyzed in this study are indeed related and represent a single pedigree that probably originated in the North Wales area of the UK. Furthermore, this single large pedigree may be of use in the identification of disease modifying loci in FTD.
BuMgNiPr2: A New Base for Stoichiometric, Position-Selective Deprotonation of Cyclopropane Carboxamides and Other Weak CH Acids This work was supported in part by Eastman Chemical. We are grateful to Z. Hantosi and C.-H. Lee for trial experiments, to I. Steele for the X-ray analyses, and to Professor S. Shuto of Hokkaido University for samples of Milnacipran precursors. (2002)

Using the irreversible formation of an alkane, the proton-removing ability of a magnesiated amine, and the activating effect of a carboxamido group, weakly acidic CH groups in a variety of systems can be selectively converted into useful amido-Grignard reagents (see scheme; DAH=dehydrated diisopropylamine).
Pathological features of glutaminase toxicity. (1980)

In an investigation of the toxicity of the anti-tumour enzyme glutaminase Rhesus monkeys, marmosets, rabbits and mice were given various doses of chemically modified glutaminase parenterally. The enzyme induced diarrhoea and dysentery and at all but the lowest doses caused illness which was fatal within 10 days. Pathological lesions produced were hepatic lipidosis and glycogen accumulation, and, in the primates, acute necrotizing colitis.
Crystalline Bacterial Cell Surface Layers (S Layers): From Supramolecular Cell Structure to Biomimetics and Nanotechnology (1999)

An astonishingly broad application potential in biotechnology, biomimetics, and nanotechnology is revealed by studies on the structure, chemistry, biosynthesis, genetics, self-assembly, and function of supramolecular surface layers (S layers). These are monomolecular, crystalline assemblies of protein or glycoprotein subunits and represent one of the most commonly observed surface structures of prokaryotic cell envelopes (see schematic representation of an archaebacterial cell envelope).
Neurosteroid Analogues. 14. Alternative Ring System Scaffolds: GABA Modulatory and Anesthetic Actions of Cyclopenta[b]phenanthrenes and Cyclopenta[b]anthracenes (2008)

Although the structural features of binding sites for neuroactive steroids on gamma-aminobutryic acid type A (GABA A) receptors are still largely unknown, structure-activity studies have established a pharmacophore for potent enhancement of GABA A receptor function by neuroactive steroids. This pharmacophore emphasizes the importance of the position and stereochemistry of hydrogen-bonding groups on the steroid. However, the importance of the steroid ring system in mediating hydrophobic interactions with the GABA A receptor is unclear. We have taken the cyclopenta[ b]phenanthrene (tetracyclic compounds with a nonlinear ring system different from that of steroids) and cyclopenta[ b]anthracene (tetracyclic molecules with a linear 6-6-6-5 carbocyclic ring system) ring systems and properly substituted them to satisfy the pharmacophore requirements of the critical hydrogen-bond donor and acceptor groups found in neuroactive steroids. We have found these cyclopenta[ b]phenanthrene and cyclopenta[ b]anthracene analogues to have potent activity at the GABA A receptor, rivaling that of the most potent steroid modulators. Single-channel analysis of electrophysiological data indicates that similarly substituted analogues in the different ring systems affect the kinetic components of macroscopic currents in different ways. Mutations to the hydrogen bonding amino acids at the putative steroid binding site (alpha1Q241L mutation and alpha1N407A/Y410F double mutation) produce similar effects on macroscopic current amplitude by the different ring system analogues suggesting that the different kinetic effects are explained by the precise interactions of each analogue with the same binding site(s).
Quest for anthelminitic agents, part II benzothiazole and benzotriazole carbamates and 2-benzazolyl vinyl ketones (1986)

Several benzthiazole carbamate analouges 12-17 and 21 of anthelminitic benzimidazole carbamates like mebendazole (1) and fenbendazole(3) are synthesised from the corresponding 2-aminobenzthiazoles. 1,2-Diamino-5,6,7,8-tetrahydronapthalene asffords through the aminonaphthimidazole 23, the carbamate 24 which is a cyclised version of parbendazole (4). 3,4-Diaminobenzophenone upon diazotisation gives the benzotriazole 25 and thence the ester 26. 2-Acetylbenzimidazole (27) and 2-acetylbenzthiazole (28) are condensed with aldehydes to give 2-benzazolyl vinyl ketones 29-34. All the products are found to be inactive in curing hamsters of N. americanus infection.
Disparate effects of insulin reduction with diltiazem on serum dehydroepiandrosterone sulfate levels in obese hypertensive men and women. (1994)

Evidence suggests that amelioration of hyperinsulinemic insulin resistance in men with calcium channel blockers of the dihydropyridine class is associated with a fall in serum insulin and a rise in serum dehydroepiandrosterone sulfate (DHEA-S) concentrations. The present study was conducted to determine whether 1) the nondihydropyridine calcium channel blocker diltiazem also reduces circulating insulin levels in humans, and 2) a reduction in circulating insulin with a calcium channel blocker is associated with a rise in serum DHEA-S concentrations in women as well as men. Ten obese hypertensive men and 13 obese hypertensive postmenopausal women were studied. Subjects were assessed at baseline and after the oral administration of diltiazem (60 mg, three times daily) for 18 days. Diltiazem treatment was associated with reductions in fasting serum insulin levels in both the men (from 91 +/- 14 to 56 +/- 12 pmol/L; P < 0.03) and women (from 92 +/- 20 to 48 +/- 9 pmol/L; P = 0.05). Serum glucose levels did not change in either group. In men, concurrent with the fall in serum insulin levels, serum DHEA-S levels rose from 4.05 +/- 1.06 to 6.91 +/- 1.32 mumol/L (P < 0.04), and serum DHEA levels rose from 14.4 +/- 3.0 to 24.3 +/- 4.6 nmol/L (P = 0.05) with diltiazem treatment, whereas serum cortisol did not change. In contrast, diltiazem administration in the women was not associated with any change in serum DHEA-S, DHEA, or cortisol levels. These observations suggest that the action of calcium channel blockers to lower fasting serum insulin levels is not specific for the dihydropyridine class and applies to both men and women. Furthermore, the finding of a sex-based disparity in DHEA-S and DHEA responses to insulin reduction suggests that the metabolism of these steroids may be regulated differently in men than in women.
Currents on generalized Yagi structures (1979)

Characteristics of currents produced on an infinite linear array of parasitic radiators when one of the radiators is excited are found. Yagi antennas use arrays of electric dipoles; detailed analyses and results are given for a generalized Yagi structure in which the dipoles are inclined at an arbitrary, angle to the array axis. These results suggest a simple mechanical means for broadbanding. Calculations are carried out within a network formulation. The integral solution obtained from this formulation is used to demonstrate the interrelation between the properties of the array of radiators excited parasitically or excited as a phased array. The solution simplifies remarkably when the angle of inclination of the dipoles is <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">54.74\deg</tex> . The surface-wave components and the (feed) correction currents are then explicitly evaluated. Although for conventional Yagi structures surface-wave solutions have been found only for capacitive dipoles, for sufficiently small angles of inclination surface waves can exist on arrays of inductive dipoles.
Role of Tissue Factor in Hemostasis, Thrombosis, and Vascular Development (2004)

Tissue factor (TF) is best known as the primary cellular initiator of blood coagulation. After vessel injury, the TF:FVIIa complex activates the coagulation protease cascade, which leads to fibrin deposition and activation of platelets. TF deficiency causes embryonic lethality in the mouse and there have been no reports of TF deficiency in humans. These results indicate that TF is essential for life, most likely because of its central role in hemostasis. In addition, aberrant TF expression within the vasculature initiates life-threatening thrombosis in various diseases, such as sepsis, atherosclerosis, and cancer. Finally, recent studies have revealed a nonhemostatic role of TF in the generation of coagulation proteases and subsequent activation of protease activated receptors (PARs) on vascular cells. This TF-dependent signaling contributes to a variety of biological processes, including inflammation, angiogenesis, metastasis, and cell migration. This review focuses on the roles of TF in hemostasis, thrombosis, and vascular development.
Viruses: Making Friends with Old Foes (2006)

The study of viruses has traditionally focused on their roles as infectious agents and as tools for understanding cell biology. Viruses are now finding a new expanded role as nanoplatforms with applications in materials science and medicine. Viruses form highly symmetrical monodisperse architectures and are ideal templates for engineering multifunctionality, including multivalent display of surface ligands and encapsulation of inorganic and organic materials. These developments assure that viruses will find applications as versatile nanoscale materials.
Does the Public Still Look at Public Displays? (2018)

Public displays are widely used for displaying information in public space, such as shopping centres. They are typically programmed to display advertisements or general information about the space in which they are situated. Due to recent advances in technology, public displays are becoming ubiquitous in space around cities and can potentially enable new interactions with public space. However, despite these advances, research reports that public displays are often found to be: (1) generally irrelevant to the space in which they are situated; and (2) ignored by passers-by. Although much research has focused on tackling these issues, a gap remains regarding knowledge about how public displays in the wild are currently being used at a time when people are increasingly relying on their smartphones as a main source for accessing information and for connecting with others. The study reported in this article aims to address this gap by presenting new insights about the current practices of non-research public displays and their role in a hyperconnected society. To achieve this, we provide results from a field observation study of non-research public displays and contextualise our findings within an analysis of related work. This article makes three main contributions: (1) identifying how user engagement with public displays has changed over the past 10 years; (2) understanding how the pervasiveness of smartphones and other connected devices has modified whether users notice public displays and their interactions with public displays; and (3) outlining design recommendations and opportunities towards making public displays more relevant in a hyperconnected society.