gebhart/patrepeval huggingface dataset:
THE COMPOSITION OF THE STRONG PHOSPHORIC ACIDS (1956)

The composition of the strong phosphoric acids was studied in the range 68.8 to 86.3% phosphorus pentoxide by weight. Improved filter-paper chromatography made possible the quantitative determination of the nine lower members of the series, and occasionally up to the twelfth member. It was found that when the strong phosphoric acids are prepared by heating at 350 °C, a dynamic equilibrium between the component acids is set up which persists when the mixtures are cooled to room temperature. Only linear condensed polyphosphoric acids were present in the range studied. The composition corresponding to 100% orthophosphoric acid contains about 6 mole percent each of pyrophosphoric acid and “free water”. As the mole ratio of water to phosphorus pentoxide decreases, the number of component acids increases. Orthophosphoric acid is present to an appreciable extent in the stronger phosphoric acids. “Hexametaphosphoric acid” is not a separate chemical entity, but a mixture of higher linear polyphosphoric acids.
Synthesis and Biological Evaluation of Novel Analogues and Prodrugs of the Cytotoxic Antibiotic CC-1065 for Selective Cancer Therapy (2002)

This paper describes novel seco-analogues 25−27 of the cytotoxic antibiotic CC-1065 (1) and their prodrugs 5, 6a, and 6b, for antibody-directed enzyme prodrug therapy (ADEPT). The partially hydrogenated seco-CCI-analogue 7 and the corresponding methyl-CCI analogues 8a and 8b were synthesized by alkylation of 9 with 15 and 16, respectively, followed by radical cyclization and deprotection. Treatment of 7, 8a, and 8b with the galactose trichloroacetimidate 21 and the bisindolyl-carboxylic acid 20 in the presence of EDC followed by solvolysis gave the desired prodrugs 5, 6a, and 6b, respectively. Compounds 25−27 were prepared by treatment of 7, 8a, and 8b with 20 after deprotection. In vitro tests showed a strong cytotoxicity for 25 and a fairly low toxicities for 26 and 27. However, the selectivity of the prodrugs 5, 6a, and 6b was not sufficient for ADEPT. Interestingly, 8a and 8b did not undergo Winstein cyclization to produce the spirocyclopropylcyclohexadienone moiety. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)
In vivo biotinylation of the vasculature in B-cell lymphoma identifies BST-2 as a target for antibody-based therapy (2009)

The discovery of accessible markers of lymphoma may facilitate the development of antibody-based therapeutic strategies. Here, we describe the results of a chemical proteomic study, based on the in vivo biotinylation of vascular proteins in lymphoma-bearing mice followed by mass spectrometric and bioinformatic analysis, to discover proteins expressed at the tissue-blood border of disseminated B-cell lymphoma. From a list of 58 proteins, which were more than 10-fold up-regulated in nodal and extranodal lymphoma lesions compared with their levels in the corresponding normal host organs, we validated BST-2 as a novel vascular marker of B-cell lymphoma, using immunochemical techniques and in vivo biodistribution studies. Furthermore, targeting BST-2 with 2 independent monoclonal antibodies delayed lymphoma growth in a syngeneic mouse model of the disease. The results of this study delineate a strategy for the treatment of systemic B-cell lymphoma in humans and suggest that anti-BST-2 antibodies may facilitate pharmacodelivery approaches that target the tumor-stroma interface.
Epigallocatechin Gallate Synergistically Enhances the Activity of Carbapenems against Methicillin-Resistant <i>Staphylococcus aureus</i> (2002)

Combinations of carbapenems and epigallocatechin gallate (EGCg; a main constituent of tea catechins) showed potent synergy against 24 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). MICs of imipenem in the presence of EGCg at 3.125, 6.25, 12.5, and 25 microg/ml, were restored to the susceptible breakpoint (< or =4 microg/ml) for 8, 38, 46, and 75% of the MRSA isolates, respectively. Similar results were also observed for combinations of panipenem or meropenem and EGCg. Therefore, the combinations may be worthy of further evaluation in vivo against MRSA infection.
Anorexic and Behavioural Effects of a New Imidazo-Isoindole Derivative (Mazindol) in Comparison with &lt;i&gt;d&lt;/i&gt;-Amphetamine in the Rat (1977)

The effect of an imidazo-isoindole derivative (mazindol) upon motor and feeding activity and two different avoidance behaviours have been compared with those of d-amphetamine in rats. It was found that both drugs depress feeding activity in a dose-related manner and increase the motor activity of the animals. However, the ratio of the lowest motility-increasing dose and the lowest appetite suppressant dose is 0.5 for d-amphetamine and 2 for mazindol. Mazindol, like d-amphetamine, caused a stereotyped behaviour in rats when given in very high doses, but the range between the anorexic and the stereotyped behaviour dose is much higher for mazindol than for d-amphetamine. The shuttle-box avoidance behaviour suppressed by tetrabenazine is completely restored by d-amphetamine and partially by mazindol. Lever-pressing avoidance suppressed by tetrabenazine is restored by d-amphetamine while mazindol at the doses used is ineffective. It is concluded that mazindol could be an anorexic agent better suited than d-amphetamine for clinical use.
Synthesis and Purification of Phosphorodithioate DNA (2003)

Oligonucleotide analogs bearing modified phosphodiester linkages have been the focus of considerable interest in the antisense field, with methylphosphonates and phosphorothioates being the most extensively studied derivatives to date (1–3). These modifications, whereby a single nonbridging oxygen atom is replaced with either a methyl group or sulfur atom, generate certain very desirable oligomer characteristics (4–7), such as resistance toward nucleases, retention of the ability to form duplexes with natural DNA or RNA, and, relative to the phosphorothioate derivative, an ability to stimulate RNase H activity. Unfortunately, and in contrast to natural DNA, the phosphorus center is rendered chiral by these substitutions. Thus, for a deoxyoligonucleotide with n phosphodiester linkages, there can be 2 n stereo-isomers with perhaps only one being the most active. Recent attempts to overcome this problem have focused on developing chemistries that either are stereoselective and generate oligomers enriched in one diastereomer (8,9) or are designed to synthesize new, phosphorus achiral analogs. In addition to being phosphorus achiral, perhaps new analogs may also have unique and attractive properties relative to the antisense area.
Amplification of a Cryptosporidium parvum gene fragment encoding thymidylate synthase. (1992)

Currently, there is no effective therapy for cryptosporidiosis and it is unclear why antifolate drugs which are effective treatments for infections caused by closely related parasites are not also effective against Cryptosporidium parvum. In protozoa, the target of these drugs, dihydrofolate reductase (DHFR), exists as a bifunctional enzyme also manifesting thymidylate synthase (TS) activity and is encoded by a fused DHFR-TS gene. In order to prepare a probe to isolate the C. parvum DHFR-TS gene we have used degenerate oligonucleotides whose sequences are based on strongly conserved regions of TS protein sequence to prime the polymerase chain reaction (PCR) with C. parvum DNA. The PCR amplified a 375-bp DNA fragment which was cloned and sequenced; the deduced amino acid sequence had significant identity with known TS sequences, including strict conservation of all phylogenetically invariant TS amino acid residues. The cloned PCR fragment was used as a probe to isolate a number of overlapping clones from a C. parvum genomic library which were definitively shown to be of cryptosporidial origin by genomic Southern and molecular karyotype analyses. The deduced protein sequence of C. parvum TS was most similar to the bifunctional TS enzymes of Plasmodium chabaudi and Plasmodium falciparum.
Estimating the usefulness of search engines (1999)

In this paper, we present a statistical method to estimate the usefulness of a search engine for any given query. The estimates can be used by a metasearch engine to choose local search engines to invoke. For a given query, the usefulness of a search engine in this paper is defined to be a combination of the number of documents in the search engine that are sufficiently similar to the query and the average similarity of these documents. Experimental results indicate that the proposed estimation method is quite accurate.
The synthesis of monomethoxy[1]benzothieno[2,3‐<i>c</i>]quinolines (1987)

Abstract A series of monomethoxy[1]benzothieno[2,3‐ c ]quinolines 24‐28 were prepared by photocylization of the appropriate 3‐chloro‐ N ‐phenylbenzo[ b ]thiophene‐2‐carboxamides 9–13 to [1]benzothieno[2,3‐ c ]quinolin‐6( 5H )‐ones 14‐18 followed by chlorination to 6‐chloro[1]benzothieno[2,3‐ c ]quinolines 19‐23 then dechlorination resulting in the title compounds except for 25 which was achieved by direct reduction of 15 . Reaction of 24‐28 with methyl iodide provided the corresponding N ‐methyl quaternary salts 29‐33 . Also, conversion of 4‐meth‐oxy[1]benzothieno[2,3‐ c ]quinolin‐6( 5H )‐one 16 to 4‐methoxy‐6‐methylthio[1]benzothieno[2,3‐ c ]quinoline 35 and 4,6‐dimethoxy[1]benzothieno[2,3‐ c ]quinoline 36 is described.
<i>Rhodococcus equi</i> infection in foals: the science of ‘rattles’ (2007)

Infection with Rhodococcus (Corynebacterium) equi is a well-recognised condition in foals that represents a consistent and serious risk worldwide. The condition manifests itself primarily as one of pulmonary abscessation and bronchitis, hence the terminology of 'rattles' derived from its most obvious clinical sign, frequently terminal when first identified. This review addresses the clinical manifestation, bacteriology and pathogenesis of the condition together with recent developments providing knowledge of the organism in terms of virulence, epidemiology, transmission and immune responses. Enhanced understanding of R. equi virulence mechanisms and biology derived from the recently available genome sequence may facilitate the rational development of a vaccine and the improvement of farm management practices used to control R. equi on stud farms in the future. Reliance on vaccines alone, in the absence of management strategies to control the on-farm challenge is likely to be disappointing.
Immunodetection of nmt55/p54nrbisoforms in human breast cancer (2001)

Our study indicates that nmt55/p54nrb protein is post-transcriptionally regulated in human breast tumors leading to reduced expression in ER- tumors and the expression of an amino terminal altered isoform in a subset of ER+ tumors. The potential involvement of nmt55/p54nrb in RNA binding and pre-mRNA splicing may be important for normal cell growth and function; thus, loss or alteration of protein structure may contribute to tumor growth and progression.
Mitochondrial dysfunction and age (2007)

Purpose of review Mitochondrial dysfunction is commonly thought to result from oxidative damage that leads to defects in the electron transport chain (ETC). In this review, we highlight new research indicating that there are early changes in mitochondrial function that precede ETC defects and are reversible thereby providing the possibility of slowing the tempo of mitochondrial aging and cell death. Recent findings Increased mitochondrial uncoupling – reduced adenosine triphosphate (ATP) produced per O2 uptake – and cell ATP depletion are evident in human muscle nearly a decade before accumulation of irreversible DNA damage that causes ETC defects. New evidence points to reduction in activators of biogenesis (e.g. PGC-1α) and to degradation of mitochondria allowing accumulation of molecular and membrane damage in aged mitochondria. The early dysfunction appears to be reversible based on improved mitochondrial function in vivo and elevated gene expression levels after exercise training. Summary New molecular and in vivo findings regarding the onset and reversibility of mitochondrial dysfunction with age indicate the potential: 1) for diagnostic tools to identify patients at risk for severe irreversible defects later in life; and 2) of an intervention to delay the tempo of aging and improve the quality of life of the elderly.
Anti-tumor Activity of Compound Derived from Diketene and Their Related Compounds (1977)

Various derivatives containing acetoacetamide, β-aminocrotonamide, pyrimidine, pyridine, dihydroxybenzoic acid, quinoline, pyridone, 2-pyrone and 2-pyrrolidone were prepared mainly from diketene. Their anti-tumor activities were examined by use of ascitic or solid type of Ehrlich carcinoma, and among them eleven compounds were found to have some anti-tumor effects on this solid tumor. These compounds were derivatives of pyrimidine (No. 30), pyridine (No. 41, 42, 54, 55, 56, 57 and 63), 2-pyrone (No. 124 and 125) and pyridopyrimidine (No. 137). No correlation was found between anti-tumor activity and these derivatives. No other substances in Table I-XII ; were effective.
THE REVISED STRUCTURE OF FURANOFUKINOL, A CONSTITUENT FROM <i>PETASITES JAPONICUS</i> MAXIM. RHIZOMES (1978)

Abstract The structure of furanofukinol, a constituent of Petasites japonicus Maxim., proposed previously as 3α,6β-dihydroxyfuranoeremophilane (V-a) should be revised to 3α,6β-dihydroxyfuranoeremophilane (I) by the PMR study of 3-O-angeloyl-6-O-acetylfuranofukinol (VIII) and by the chemical conversion of furanofukinol to 3β-hydroxyeremophilanes (X-a,b). The structures of the two related sesquiterpenes, isolated from Farfugium hiberniflorum Kitam., must therefore be revised to 3β-angeloyloxy-6β-hydroxyfuranoeremophilane (VII) and 3β-angeloyloxy-6β-acetoxyfuranoeremophilane (VIII).
New Guanidinium-based Room-temperature Ionic Liquids. Substituent and Anion Effect on Density and Solubility in Water (2010)

In order to examine the influence of the alkyl chain length on some physical properties of guanidinium salts, the synthesis of a homologous series of new N″-n-alkylsubstituted N,N-diethyl-N′ ,N′- di-n-propyl-N″-n-hexyl guanidinium ionic liquids (gILs), containing chloride (Cl), tetrafluoroborate (BF 4 ), acesulfamate (Ace), saccharinate (Sac), and tosylate (Tos) as anions, is reported. C n -gILAce, C n -gILSac, and C n -gILBF 4 were obtained by ion exchange reaction of the corresponding hexasubstituted guanidinium chlorides (C n -gCl, n = 3, 4, 6, 8, 10), which were synthesized by a quaternization reaction of the pentaalkyl-substituted guanidine 3 and the corresponding alkylchloride in DMF. The tosylates gILs C n -gTos (n = 1, 2, 4, 6, 8, 10) were synthesized by alkylation of 3 with the corresponding alkyltosylates. Some physical properties, such as solubility in water and organic solvents, refractive index and density, are considered as a function of the length of the n-alkyl substituent R and the nature of the anion
A multichannel compression strategy for a digital hearing aid (2002)

Multi-channel compression schemes are a practical methods of mapping the wide dynamic range of speech signals into the reduced dynamic range of hearing impaired listeners. These systems address two of the shortcomings of single-channel compression systems: (1) the reduction of gain as a result of narrow-band non-speech stimuli and (2) the reduction of gain that often occurs when high-frequency speech components are followed by intense low-frequency speech components. They also provide frequency-dependent compression ratios that are needed by many newer supra-threshold fitting strategies (e.g., DSL I/O). This paper presents a multichannel compression scheme that employs an oversampled, polyphase DFT filterbank. In each compressor channel, the gain is controlled by an adjustable combination of a overall, dual time-constant input signal level and the individual channel signal level that is measured with a short time-constant RMS detector. Informal listening tests have demonstrated that the design has very good audio quality and performs well in real-world listening situations. The design is suited for low-power, real-time operation.
Design of an integrated OLED driver for a modular large-area lighting system (2013)

The concept of a flexible, large-area, OLED-based lighting system with a modular structure and built-in intelligent light management is introduced. The paper describes the design of a high-voltage integrated circuit for driving and controlling an individual OLED tile in this modular lighting system. The chip comprises a switching DC-DC buck converter for generating the OLED current and a sensitive analog feedback loop for adjusting the duty cycle of the converter’s PWM control signal. The chip was designed in the 80V 0.35µm I3T80 technology of ON Semiconductor.
Vaccination trial with HPV16 L1E7 chimeric virus‐like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3) (2007)

Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus-like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric virus-like particles (CVLP) consist of a carboxy-terminally truncated HPV16L1 protein fused to the amino-terminal part of the HPV16 E7 protein and self-assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1- and E7-specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A randomized, double blind, placebo-controlled clinical trial has been conducted in 39 HPV16 mono-infected high grade cervical intraepithelial neoplasia (CIN) patients (CIN 2/3). Two doses (75 mug or 250 mug) of CVLP were applied. The duration of the study was 24 weeks with 2 optional visits after another 12 and 24 weeks. The vaccine showed a very good safety profile with only minor adverse events attributable to the immunization. Antibodies with high titers against HPV16 L1 and low titers against HPV16 E7 as well as cellular immune responses against both proteins were induced. Responses were equivalent for both vaccine concentrations. A trend for histological improvement to CIN 1 or normal was seen in 39% of the patients receiving the vaccine and only 25% of the placebo recipients. Fifty-six percent of the responders were also HPV16 DNA-negative by the end of the study. Therefore, we demonstrated evidence for safety and a nonsignificant trend for the clinical efficacy of the HPV16 L1E7 CVLP vaccine.
A Diffusion Barrier Charcoal Adsorption Collector for Measuring Rn Concentrations in Indoor Air (1986)

Development of a practical detector for collecting Rn by adsorption in charcoal with a time integration of 2 d or more, achieved by use of a diffusion barrier through which Rn enters, is described. The sensitivity is adequate for monitoring Rn levels in houses. It is easily sent and returned by mail, and instructions for use are simple enough for any householder to follow. The cost per measurement is apparently well below that for competitive techniques.
Preparation of biologically active platelet-derived growth factor type BB from a fusion protein expressed in Escherichia (1989)

Preparations of the mitogen platelet-derived growth factor (PDGF) from human platelets contain two related polypeptides termed A chain and B chain. PDGF-B is highly homologous to a portion of p28v-sis, the transforming protein of simian sarcoma virus. We have studied the mitogenic potential of a PDGF-BB-like homodimer by expressing the sequence coding for the mature part of PDGF-B in Escherichia coli. Expression was achieved as cro-beta-gal-PDGF-B fusion protein which was exclusively found in the "inclusion bodies". A monomeric PDGF-B fragment shortened by 12 amino acid residues from the NH2 terminus was excised from the fusion protein by CNBr cleavage. After protection of thiols by S-sulfonation, this fragment was purified by gel permeation chromatography and reversed-phase high-performance liquid chromatography. This monomeric protein was dimerized in the presence of a mixture of reduced and oxidized glutathione to yield biologically active rPDGF-BB with an overall yield of approximately 0.7 mg of rPDGF-BB/L of culture. Escherichia coli rPDGF-BB stimulated [3H]thymidine incorporation into AKR2B fibroblast at concentrations of about 1 ng/mL.
A general procedure for isotopic (deuterium) labelling of non‐steroidal antiinflammatory 2‐arylpropionic acids (1994)

Abstract Alkaline treatment of nonsteroidal antiinflammatory 2‐arylpropionic acids in deuterium oxide led in all cases to isotopic exchange of the proton located at the α‐position of the side chain. Monodeuteration was observed in the case of carprofen, ibuprofen, ketoprofen, fenoprofen, flurbiprofen and naproxen. Additional exchange of one or two protons of the heterocyclic ring occurred in indoprofen, suprofen and tiaprofenic acid. The isotopic labelling survived under the conditions required to perform in vitro photoallergic studies (photolysis in non‐deuterated aqueous media).
Cholera toxin acts as a potent adjuvant for the induction of cytotoxic T-lymphocyte responses with non-replicating antigens. (1994)

Cholera toxin (CT) is a strong systemic and mucosal adjuvant that greatly enhances IgG and IgA immune responses, but its adjuvant effects for cellular immunity, particularly class I-restricted cytotoxic T lymphocyte (CTL) responses, are less well understood. In the present report, CT and the purified non-toxic B component (CTB) were assessed for their ability to facilitate class I-restricted CTL induction to soluble proteins as well as to permit sensitization of target cells for CTL-mediated lysis. Priming for ovalbumin (OVA)-specific CTL occurred following oral exposure to a combination of OVA with CT plus CTB. In addition, CTB mixed with soluble proteins and administered intravenously primed mice for antigen-specific class I-restricted CTL. Target cells could also be sensitized for CTL-mediated killing following their exposure to soluble antigen and CTB in vitro. These results indicate that combinations of CT and CTB not only enhance antibody responses, but also have an immunomodulating effect to allow sensitization and priming for antigen-specific class I-restricted CTL.
Bio-sulphite pulping with ceriporiopsis subvermispora (1996)

Increase of productivity and product quality as well as energy savings and improvement of the environmental impact are main strategies of the pulp and paper production in the nineties. Biotechnological processes are consistent with these strategies and are getting access to this industry. Pretreatment of wood chips with selectively delignifying white rot fungi, called biopulping, was found to assist the sulphite cooking process, leading to reduced kappa numbers and an increase in brightness of pulp. The results obtained with the fungus Ceriporiopsis subvermispora on laboratory and small pilot scale will be reported. Emphasis will be put on the ergosterol assay to determine the development of fungal biomass in wood chips and its correlation with parameters of the solid substrate fermentation. The chemical background will be discussed.