gebhart/patrepeval huggingface dataset:
LPSH - Some observations and comments (2000)

The Leadership Programme for Serving Headteachers (LPSH) was developed by business consultants Hay McBer in association with the National Association of Headteachers (NAHT) and the Open University on behalf of the Teacher Training Agency (TTA). The programme, which has now been running since 1998, is based on the assessment and subsequent development of a number of competencies which have been identified through examination of the key features of headteachers in highly effective schools. The LPSH has received enthusiastic praise from participants on the programme who generally seem very satisfied with a process that provides them with a rigorous self-evaluation supplemented by high quality training conducted in pleasant surroundings. In this article it is my intention to examine both the basic tenets of the LPSH programme and the development materials recommended for participants. The observations and comments that emerge from that examination will demonstrate a number of concerns that should be addressed by the new National College for School Leadership, due to take responsibility for headship development in the Autumn of 2000.
Continuity Properties of Paretian Utility (1964)

Abstract : In the study of real-valued representations (Paretian utility functions) of a completely preordered space (Space of actions preordered by preferences), the continuity properties of the representation can be made to rest on the following result. R will denote the extended real line, i.e., the real line with negative infinity and positive infinity adjoined. A degenerate set is a set having at most one element. Given a subset S of R, a lacuna of S is a non-degenerate interval of R without points of S but having a lower bound and an upper bound in S; a gap of S is a maximal lacuna of S. (Author)
Antiviral Chemotherapy and Chemoprophylaxis (1985)

Antiviral compounds have been developed for use in chemoprophylaxis and chemotherapy of a variety of infections in humans, including those caused by influenza viruses, respiratory syncytial virus, and herpesviruses. The efficacy of several of these compounds has been demonstrated in rigorously controlled trials. Advances in molecular virology have led to the identification of biochemically defined, virus-specific functions that serve as appropriate targets for the future development of antiviral compounds. Clinical investigators and practicing physicians are now confronting questions previously raised with the use of antibacterial antibiotics. These questions concern appropriate routes of administration for antiviral compounds, optimal dosage regimens, risks of long-term prophylaxis, and the emergence of resistant organisms.
A β 2 Adrenergic Receptor Signaling Complex Assembled with the Ca 2+ Channel Ca v 1.2 (2001)

The existence of a large number of receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) raises the question of how a particular receptor selectively regulates specific targets. We provide insight into this question by identifying a prototypical macromolecular signaling complex. The beta(2) adrenergic receptor was found to be directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(v)1.2. This complex also contained a G protein, an adenylyl cyclase, cyclic adenosine monophosphate-dependent protein kinase, and the counterbalancing phosphatase PP2A. Our electrophysiological recordings from hippocampal neurons demonstrate highly localized signal transduction from the receptor to the channel. The assembly of this signaling complex provides a mechanism that ensures specific and rapid signaling by a G protein-coupled receptor.
Alcohol cue reactivity: effects of detoxification and extended exposure. (1993)

Alcoholics' reactions to drinking-related stimuli (cue reactivity) have been well documented and alcohol cue exposure treatment has been conducted recently in several clinical trials. Prior to conducting large-scale clinical trials it is important to know what effects detoxification may have on cue reactivity. However, no information is available about the effects of stage of detoxification or of detoxification medication on alcohol cue reactivity. In this study, 45 male alcoholics, detoxified without medication, were assessed during either their second, fourth or sixth day of withdrawal. Further, their reactivity was compared to that of alcoholics detoxified with chlordiazepoxide (n = 15), and to that of alcoholics in their fourth week after drinking (n = 28). Cue reactivity assessment investigated salivation and urge to drink after 3 minutes of water cue exposure and then after 3 minutes of alcohol cue exposure. Urges to drink were assessed during an additional 15 minutes of alcohol exposure to explore latency to maximum reactivity and habituation. Reactivity did not differ as a function of group membership, although salivation was elevated to both beverages during the first week of detoxification. Of the sample, 70% reacted to alcohol with increased urge and 65% with increased salivation, with no difference between groups in proportions of reactors. The maximum urge to drink occurred in the first 6 minutes of alcohol exposure, followed by a gradual and significant decrease. There were no differences on these measures between alcoholics in their first or fourth week after their last drink. Implications for theory and clinical applications are discussed.
Characterization of methyltransferase and hydroxylase genes involved in the biosynthesis of the immunosuppressants FK506 and FK520 (1996)

FK506 and FK520 are 23-membered macrocyclic polyketides with potent immunosuppressive and antifungal activities. The gene encoding 31-O-demethyl-FK506 methyltransferase, fkbM, was isolated from Streptomyces sp. strains MA6858 and MA6548, two FK506 producers, and Streptomyces hygroscopicus subsp. ascomyceticus, an FK520 producer. The nucleotide sequence of the fkbM gene revealed an open reading frame encoding a polypeptide of 260 amino acids. Disruption of fkbM in Streptomyces sp. strain MA6548 yielded a mutant that produced 31-O-demethyl-FK506, confirming the involvement of the isolated genes in the biosynthesis of FK506 and FK520. Heterologous expression of fkbM in Streptomyces lividans established that fkbM encodes an O-methyltransferase catalyzing the methylation of the C-31 hydroxyl group of 31-O-demethyl-FK506 and FK520. A second open reading frame, fkbD, was found upstream of fkbM in all three aforementioned species and was predicted to encode a protein of 388 residues that showed a strong resemblance to cytochrome P-450 hydroxylases. Disruption of fkbD had a polar effect on the synthesis of the downstream fkbM gene product and resulted in the formation of 9-deoxo-31-O-demethyl-FK506. This established the product of fkbD as the cytochrome P-450 9-deoxo-FK506 hydroxylase, which is responsible for hydroxylation at position C-9 of the FK506 and FK520 macrolactone ring.
Chemical Modification Study of Antisense Gapmers (2012)

A series of insertion patterns for chemically modified nucleotides [2'-O-methyl (2'-OMe), 2'-fluoro (2'-F), methoxyethyl (MOE), locked nucleic acid (LNA), and G-Clamp] within antisense gapmers is studied in vitro and in vivo in the context of the glucocorticoid receptor. Correlation between lipid transfection and unassisted (gymnotic--using no transfection agent) in vitro assays is seen to be dependent on the chemical modification, with the in vivo results corresponding to the unassisted assay in vitro. While in vitro mRNA knockdown assays are typically reasonable predictors of in vivo results, G-Clamp modified antisense oligonucleotides have poor in vivo mRNA knockdown as compared to transfected cell based assays. For LNA gapmers, knockdown is seen to be highly sensitive to the length of the antisense and number of LNA insertions, with longer 5LNA-10DNA-5LNA compounds giving less activity than 3LNA-10DNA-3LNA derivatives. Additionally, the degree of hepatoxicity for antisense gapmers with identical sequences was seen to vary widely with only subtle changes in the chemical modification pattern. While the optimization of knockdown and hepatic effects remains a sequence specific exercise, general trends emerge around preferred physical properties and modification patterns.
Effect of Troglitazone in Insulin-Treated Patients with Type II Diabetes Mellitus (1998)

When given in conjunction with insulin, troglitazone improves glycemic control in patients with type 2 diabetes mellitus.
Micromechanical comb actuators with low driving voltage (1992)

Comb actuators with submicrometer-wide suspensions have been fabricated and tested. Measurements proved that they are reliable devices for displacements in the range of several micrometers with a precision in the tens of nanometers. Due to the very flexible suspensions (10 mN m-1) only low voltages-around 20 V- were required for the actuation. As an application, the author have fabricated and characterized an xy microstage which allows precise two-dimensional positioning. The limits of the devices were also tested. A main source of problems is the sticking phenomenon. Depending on the design of the actuator, the movable comb will, at a critical voltage, either stick on the sides of the fixed fingers (side sticking) or on the front ends of the fixed finger (front sticking). Analytical calculations, simulation and measurements are compared.
Contrasting histories: Northern and Southern Vietnam (2012)

One country but two different histories: that is the extraordinary story of Vietnam. The northern and southern Vietnamese have separate ethnic backgrounds. In the north the people were originally Australo-Melanesians from at least 30,000 years ago and Viet from about 3000 years ago, but in the south the inhabitants were first Austro-Asiatic, then Austro-Melanesian under the Cham. Today the south Vietnamese are a mixture of Cham, Mon-Khmer and Viet. Their accents, their cooking and their clothing are different but the language they speak and write is the same. The Viet, who are now the largest ethnic group in Vietnam, have gradually moved down from northern Vietnam over the centuries in their nam tien or 'southward march'.
Phosphorylation and assembly of nicotinic acetylcholine receptor subunits in cultured chick muscle cells. (1987)

The assembly of the nicotinic acetylcholine receptor (AChR), an oligomeric cell surface protein, was studied in cultured muscle cells. To measure this process, the incorporation of metabolically labeled alpha-subunit into oligomeric AChR was monitored in pulse-chase experiments, either by the shift of this subunit from the unassembled (5 S) to the assembled (9 S) position in sucrose density gradients, or by its coprecipitation with antisera specific for the delta-subunit. We have found that AChR assembly is initiated 15-30 min after subunit biosynthesis and is completed within the next 60 min. The alpha-subunit is not overproduced, as all detectable pulse-labeled alpha-subunit can be chased into the oligomeric complex, suggesting that AChR assembly in this system is an efficient process. The rate of AChR assembly is decreased by metabolic inhibitors and by monensin, an ionophore that impairs the Golgi apparatus. We have observed that the gamma- and delta-subunits of AChR are phosphorylated in vivo. The delta-subunit is more highly phosphorylated in the unassembled than in the assembled state, indicating that its phosphorylation precedes assembly and that its dephosphorylation is concomitant with AChR assembly. These findings suggest that subunit assembly occurs in the Golgi apparatus and that phosphorylation/dephosphorylation mechanisms play a role in the control of AChR subunit assembly.
A theory for multiresolution signal decomposition: the wavelet representation (1989)

Multiresolution representations are effective for analyzing the information content of images. The properties of the operator which approximates a signal at a given resolution were studied. It is shown that the difference of information between the approximation of a signal at the resolutions 2/sup j+1/ and 2/sup j/ (where j is an integer) can be extracted by decomposing this signal on a wavelet orthonormal basis of L/sup 2/(R/sup n/), the vector space of measurable, square-integrable n-dimensional functions. In L/sup 2/(R), a wavelet orthonormal basis is a family of functions which is built by dilating and translating a unique function psi (x). This decomposition defines an orthogonal multiresolution representation called a wavelet representation. It is computed with a pyramidal algorithm based on convolutions with quadrature mirror filters. Wavelet representation lies between the spatial and Fourier domains. For images, the wavelet representation differentiates several spatial orientations. The application of this representation to data compression in image coding, texture discrimination and fractal analysis is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Modification of the Respiratory Syncytial Virus F Protein in Virus-Like Particles Impacts Generation of B Cell Memory (2014)

The development of vaccines for respiratory syncytial virus (RSV) is hampered by a lack of a clear understanding of the requirements for eliciting protective as well as durable human immune responses to virus antigens. The results of this study indicate that the form of the RSV F protein has a direct and significant impact on the type of anti-F-protein IgG antibodies induced and the generation of F-protein-specific memory. Identification of the conformation of the RSV F protein that most effectively stimulates not only LLPCs and but also memory B cells will be important in the future development of RSV vaccines.
The dhb Operon of Bacillus subtilisEncodes the Biosynthetic Template for the Catecholic Siderophore 2,3-Dihydroxybenzoate-Glycine-Threonine Trimeric Ester Bacillibactin (2001)

Bacillus subtilis was reported to produce the catecholic siderophore itoic acid (2,3-dihydroxybenzoate (DHB)-glycine) in response to iron deprivation. However, by inspecting the DNA sequences of the genes dhbE, dhbB, and dhbF as annotated by the B. subtilis genome project to encode the synthetase complex for the siderophore assembly, various sequence errors within the dhbF gene were predicted and confirmed by re-sequencing. According to the corrected sequence, dhbF encodes a dimodular instead of a monomodular nonribosomal peptide synthetase. We have heterologously expressed, purified, and assayed the substrate selectivity of the recombinant proteins DhbB, DhbE, and DhbF. DhbE, a stand-alone adenylation domain of 59.9 kDa, activates, in an ATP-dependent reaction, DHB, which is subsequently transferred to the free thiol group of the cofactor phosphopantetheine of the bifunctional isochorismate lyase/aryl carrier protein DhbB. The third synthetase, DhbF, is a dimodular nonribosomal peptide synthetase of 264 kDa that specifically adenylates threonine and, to a lesser extent, glycine and that covalently loads both amino acids onto their corresponding peptidyl carrier domains. To functionally link the dhb gene cluster to siderophore synthesis, we have disrupted the dhbF gene. Comparative mass spectrometric analysis of culture extracts from both the wild type and the dhbF mutant led to the identification of a mass peak at m/z 881 ([M-H](1-)) that corresponds to a cyclic trimeric ester of DHB-glycine-threonine.
A surrounding isolation-merged plate electrode (SIMPLE) cell with checkered layout for 256 Mbit DRAMs and beyond (2002)

The authors describe a novel cell structure called a surrounding isolation merged plate electrode (SIMPLE) cell. In this cell, close-packed silicon pillars are laid out checker-wise, and a thin isolation-merged plate electrode surrounds the pillars. This cell structure leads to cell area reduction to 50%, trench depth reduction to 50%, and planarization and process step reduction compared with the conventional trench type cell. Using the design rule of 64 Mbit DRAM (dynamic RAM) (0.35 mu m), the SIMPLE cell can achieve a cell area of 256 Mbit DRAM (0.5 mu m/sup 2/). The SIMPLE cell is an attractive candidate for 256 Mbit DRAMs and beyond.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A phase I trial of intravenous liposomal irinotecan in patients with recurrent high-grade gliomas. (2015)

2029 Background: Treatment options for recurrent malignant glioma are limited. Preclinical activity of irinotecan has been seen in glioma models but only modest efficacy has been noted in clinical studies, perhaps related to drug distribution and/or pharmacokinetic limitations. In preclinical testing, liposomal irinotecan (nal-IRI, also MM-398, PEP02) demonstrates prolongation of drug exposure and higher tissue levels of drug due to slower metabolism. A Phase I study was undertaken in advanced solid tumor patients in Taiwan, and the MTD was 120 mg/m2; UGT1A1 genotyping was not prospectively undertaken in that solid tumor study. Objectives: To assess the safety and pharmacokinetics (PK) of nal-IRI and to determine the maximum tolerated dose (MTD) in patients with recurrent malignant glioma stratified based on UGT1A1 genotyping. Methods: This Phase I study in recurrent malignant glioma stratified patients by UGT1A1 status, to homozygous WT (“WT”) vs heterozygous WT/*28 (“HT”). Patients who were homozygous *28 were ineligible. Eligibility criteria included age > = 18, KPS > = 60, not on enzyme-inducing drugs (including enzyme-inducing seizure medications), and no prior treatment with irinotecan. The design was a standard 3+3 Phase I design. Patients who were WT were started at 120 mg/m2 (the MTD from the Taiwanese study) with dose increases in 60 mg/m2 increments. Patients who were HT were started at 60 mg/m2, with dose increases in 30 mg/m2increments. Dosing was given IV every 3 weeks. The DLT assessment period was 1 cycle (21 days). Results: In the WT cohort, the MTD was 120 mg/m2. In the HT cohort, the MTD was 150 mg/m2. DLTs in both cohorts included diarrhea, some with associated dehydration and/or fatigue. Analysis of PK data is in process, and will be presented at the meeting. Conclusions: Nal-IRI had no unexpected toxicities when given via IV. The toxicity profile of the drug was felt acceptable to move forward with additional testing using convection-enhanced delivery into intracranial tumors, and such a Phase I study is currently enrolling at our institution. Clinical trial information: NCT00734682.
A base matrix method to construct column weight 3 quasi-cyclic LDPC codes with high girth (2016)

This article presents a simple, less computational complexity method for constructing exponent matrix (3, K) of girth 8, 10 and 12 of quasi-cyclic low-density parity-check codes (QC-LDPC) based on generation of base matrix. The construction of code deals with generation of base matrix by a simple algorithm and element wise element method for girth 8, while only element wise element method for girth 10 and 12. These methods are flexible for block-column length K. The simulations are shown in comparison with some existing appreciable work.
Lipoprotein nature of Bacillus licheniformis membrane penicillinase. (1981)

Membrane penicillinase (penicillin amido-beta-lactamhydrolase, EC 3.5.2.6) from Bacillus licheniformis bears a striking resemblance to the major outer membrane lipoprotein of Escherichia coli. It can be specifically labeled in vivo with [3H]glycerol, [35S]cysteine, or [3H]palmitate but not by [32P]orthophosphate. The labeled residues are located at or near the NH2 terminus of the membrane penicillinase because they can be completely removed by trypsin which cleaves a hydrophobic peptide(s) from the NH2 terminus, thereby rendering the enzyme hydrophilic. The membrane penicillinase produced by the 749/C gene carried in E. coli on phage lambda is similar to the enzyme formed in strain 749/C itself. The peptide antibiotic globomycin, which prevents processing of the E. coli prolipoprotein, severely inhibited the attachment of [3H]palmitate or [3H]glycerol to the 749/C enzyme (either in B. licheniformis 749/C or in E. coli), blocked the accumulation of penicillinase in the plasma membrane, and enhanced the formation of exoenzyme. Under the same conditions, globomycin does not prevent the attachment of palmitate or glycerol to the E. coli prolipoprotein but inhibits processing of the modified precursor to the mature lipoprotein. These results are in contrast with the lack of effect of globomycin on the RTEM-beta-lactamase of E. coli which has no detectable hydrophobic membrane form and was not labeled with palmitate or glycerol.
Antisense sequence-directed cross-linking of RNA oligonucleotides by mitomycin. (1997)

Conjugates of mitomycin C (MC) and 15-mer oligodeoxyribonucleotides (ODNs) were synthesized in which the 7-amino group of MC was tethered by either a (-CH2-)6 or a (-CH2-)12 linker to the 5'-terminal phosphate of the ODNs. The conjugates were shown to be cross-linked selectively to complementary 18-mer oligoribonucleotides (ORNs). The cross-linking was dependent on reductive activation of the MC moiety of the conjugates by NADPH-cytochrome c reductase/NADPH. The cross-linked ODN-ORN hybrid duplexes were characterized as such by degeneration by RNase H. Cross-linking efficiencies of the conjugates were 50 and 25% in the case of the (-CH2-)12 tether and the (-CH2-)6 tether respectively The results demonstrate the feasibility of sequence-targeted alkylation of RNA by MC via antisense recognition.
Vitamin E prevents diabetes-induced abnormal retinal blood flow via the diacylglycerol-protein kinase C pathway (1995)

We have characterized effects of d-alpha-tocopherol (vitamin E) on activation of protein kinase C (PKC) and diacylglycerol (DAG) levels in retinal tissues of diabetic rats and correlated its effects to diabetes-induced changes in retinal hemodynamics. Membrane PKC specific activities were increased by 71% in streptozocin-induced diabetic rats compared with controls (P < 0.05). Western blot analysis showed that membrane PKC-beta II was increased by 133 +/- 5% (P < 0.05). Injection of d-alpha-tocopherol (40 mg/kg ip) every other day prevented the increases in membrane PKC specific activity and PKC-beta II protein by immunoblots. Diabetes-induced increases in DAG levels were also normalized by d-alpha-tocopherol treatment of 2 wk duration. Physiologically, angiographic abnormalities of retinal hemodynamics based on computerized video-based fluorescein angiography and associated with increases of DAG and membranous PKC levels were also prevented by d-alpha-tocopherol treatment in diabetic rats. The effect of d-alpha-tocopherol on retinal vascular cells was also studied. Exposure of retinal endothelial cells to 22 mM glucose for 3 days increased total DAG and [3H]palmitate-labeled DAG levels by 35 +/- 8 and 50 +/- 8% (P < 0.05), respectively, compared with exposure to 5.5 mM glucose. The presence of d-alpha-tocopherol (50 micrograms/ml) prevented the increases in total DAG and [3H]palmitate-labeled DAG levels in cells exposed to 22 mM glucose. These findings suggested that treatment with d-alpha-tocopherol can prevent diabetes-induced abnormalities in rat retinal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Direct Asymmetric α‐Fluorination of Aldehydes (2005)

Linear and branched aldehydes are asymmetrically α-fluorinated with L-proline- and pyrrolidine-based organocatalysts (see scheme; NFSi: N-fluorobenzenesulfonamide). In the first case, yields and enantioselectivities were high; in the second, the yields remained high and the enantioselectivities were moderate. Significantly, linear aldehydes were only monofluorinated.