gebhart/patrepeval huggingface dataset:
Ligand-Independent and Tissue-Selective Androgen Receptor Inhibition by Pyrvinium (2013)

Pyrvinium pamoate (PP) is a potent noncompetitive inhibitor of the androgen receptor (AR). Using a novel method of target identification, we demonstrate that AR is a direct target of PP in prostate cancer cells. We demonstrate that PP inhibits AR activity via the highly conserved DNA binding domain (DBD), the only AR inhibitor that functions via this domain. Furthermore, computational modeling predicts that pyrvinium binds at the interface of the DBD dimer and the minor groove of the AR response element. Because PP acts through the DBD, PP is able to inhibit the constitutive activity of AR splice variants, which are thought to contribute to the growth of castration resistant prostate cancer (CRPC). PP also inhibits androgen-independent AR activation by HER2 kinase. The antiandrogen activity of pyrvinium manifests in the ability to inhibit the in vivo growth of CRPC xenografts that express AR splice variants. Interestingly, PP was most potent in cells with endogenous AR expression derived from prostate or bone. PP was able to inhibit several other hormone nuclear receptors (NRs) but not structurally unrelated transcription factors. PP inhibition of other NRs was similarly cell-type selective. Using dual-energy X-ray absorptiometry, we demonstrate that the cell-type specificity of PP manifests in tissue-selective inhibition of AR activity in mice, as PP decreases prostate weight and bone mineral density but does not affect lean body mass. Our results suggest that the noncompetitive AR inhibitor pyrvinium has significant potential to treat CRPC, including cancers driven by ligand-independent AR signaling.
The calf 5‘- to 3‘-exonuclease is also an endonuclease with both activities dependent on primers annealed upstream of the point of cleavage. (1994)

The catalytic activity of the calf thymus 5'- to 3'-exonuclease was measured on substrates consisting of two primers annealed adjacent to each other on a template. Exonucleolytic degradation of the downstream primer is very slow if the primers are separated by a gap of one nucleotide or if no upstream primer is present. When only a nick separates the primers, degradation is rapid. This suggests that the nuclease is designed to work with calf DNA polymerases such that synthesis from an upstream primer creates the favored nuclease substrate. Nuclease action then destroys the substrate, but it is regenerated by further polymerization. This process, termed nick translation, is necessary for both DNA replication and repair. If the downstream primer has an unannealed 5'-region, that region is removed by an endonuclease activity residing in the same enzyme. Efficient endonuclease action also requires an upstream primer that is annealed such that its 3'-end is directly adjacent to the annealed region of the downstream primer. This reaction is likely to be important for removal of DNA segments that are damaged such that exonuclease cleavage of the damaged site is not possible.
A BROAD SPECTRUM ARTIFICIAL SEA WATER MEDIUM FOR COASTAL AND OPEN OCEAN PHYTOPLANKTON 1 (1980)

ABSTRACT A new artificial seawater medium has been tested with 83 strains of coastal and open ocean phytoplankton from 11 different algal classes. The cultures were carried through four transfers, representing a period of eight weeks for most species. Only three species could not be maintained in the enriched artificial seawater, and 16 species, mainly from the Prymnesiophyceae and Dinophyceae, had reduced final cell yields compared to those grown in enriched natural seawater. Since 77% of the species tested grew equally well in enriched artificial or natural seawater and more than 95% could be maintained in the artificial medium, this recipe is useful over a broad spectrum of species. The artificial seawater base was enriched with a modified ES enrichment solution; the primary modifications were the omission of Tris and the addition of Si. Enriched medium was autoclaved without precipitation by lowering the pH before autoclaving. This was accomplished by adding equimolar amounts of Na‐HCO 3 and HCl which produced NaCl and CO 2 during the heating process. When no pH buffer was used, precipitation could only be avoided by autoclaving the artificial seawater base as two separate salt solutions (with Ca and Sr separated from CO 3 −2 and SO 4 −2 ), cooling, mixing and aseptically adding the sterilized enrichment solution.
Etanercept in Alzheimer disease (2015)

This study shows Class I evidence that weekly subcutaneous etanercept is well tolerated in Alzheimer disease dementia.
Isolated iodine images using spatial‐frequency encoding (1979)

A system has been implemented for imaging subtle amounts of iodine. Using a grating, information is encoded representing the transmission on either side of the iodine K edge. The information is decoded by filtering and processing the signal on a drum scanner. Experimental results are shown using a thyroid phantom and a rat. This system can be used in a number of studies including hepatography, the radiographic visualization of the liver.
High Surface Area Calcium Carbonate:  Pore Structural Properties and Sulfation Characteristics (1997)

Limestone or calcium carbonate (CaCO3) used as a sorbent in the removal of acid gas precursors (SO2) from combustion systems suffers from poor pore structural properties which causes low reactivity and incomplete utilization. The surface area and pore size distribution of CaCO3, if tailored appropriately, can considerably enhance its reactivity for SO2. This study focuses on the optimization of pore properties of CaCO3 particles and the enhancement of SO2 reactivity and ultimate utilization. The carbonate is produced by precipitation from an aqueous suspension of calcium hydroxide by injecting CO2. The influence of operating parameters, suspension concentration, gas flow rate, and additives (surfactant) on the surface area and pore volume is investigated. The surface area of the carbonate powder can be controlled in the range of 10−70 m2/g by varying the operating parameters. The SO2 reactivity and the ultimate utilization of the calcium carbonate indicate a dramatic improvement and can be correlated with the surface area and pore volume characteristics of the particles.
Development of an Implanted RFID Impedance Sensor for Detecting Gastroesophageal Reflux (2007)

A new method to detect gastroesophageal reflux is presented. Based on passive RFID principles, the impedance of the refluxate can be determined. We have designed and fabricated planar coils integrated with electrodes on flexible substrates using standard photolithography processes. The device can be implanted in the esophagus using currently available clinical techniques. In vitro experiments with simulated stomach acid were conducted. An approach to integrate the sensor with RFID systems is proposed. This device can help diagnose gastroesophageal reflux disease effectively.
CHANGES IN SURFACE PROPERTIES OF POLY (ETHYLENE TEREPHTHALATE) TREATED WITH LOW TEMPERATURE PLASMA: EFFECT OF PRETREATMENT WITH DIMETHYLFORMAMIDE (1986)

Modification of poly(ethylene terephthalate) (PET) fabric with low temperature oxygen plasma has been studied. Prior to the plasma modification, the fabric was treated with a strongly-interacting solvent, dimethylformamide (DMF). The effect of the prior DMF treatment on the subsequent plasma treatment was examined. The plasma-treated sample was characterized by X-ray photoelectron spectroscopy and viewed under a scanning electron microscope. Also wettability and loss in weight after plasma treatment were measured. The oxidative functionalization, surface roughness, and wettability are significantly larger for the sample which has received DMF treatment prior to the plasma treatment than that treated solely with the plasma. Furthermore, DMF-treated PET is much more subjected to etching after plasma treatment than the DMF-untreated sample and hence the weight loss of the former sample is larger than that of the latter one. DMF followed by plasma treatment leads to significant effect on the surface morphology. DMF-induced plastisization in PET causes a marked influence on the subsequent plasma modification.
An intact histone 3'-processing site is required for transcription termination in a mouse histone H2a gene. (1991)

A transcription termination site has been characterized between the mouse histone H2a-614 and H3-614 genes. There is a poly(A)- RNA present in small amounts in the nucleus which ends 600 nucleotides 3' to the H2a-614 gene. Nuclear transcription studies demonstrate that transcription extends at least 600 nucleotides 3' to the gene but is greatly reduced 700 nucleotides 3' to the gene. If all or part of the normal 3'-processing signal, consisting of the stem-loop and the U7 small nuclear ribonucleoprotein binding site, is deleted, transcription then continues past the putative termination site and RNAs which end at the 3' end of the downstream H3-614 gene accumulate. Insertion of a 150-nucleotide fragment containing the termination site between the histone 3' end and downstream polyadenylation sites reduces usage of polyadenylation sites 85 to 90%. Taken together these results suggest there is a transcription termination site which requires an intact histone 3'-processing signal to function.
Molecular Size Modulates Pharmacokinetics, Biodistribution, and Renal Deposition of the Drug Delivery Biopolymer Elastin-like Polypeptide (2018)

Elastin-like polypeptides (ELP) are engineered proteins that consist of repetitions of a five amino acid motif, and their composition is easily modified to adjust their physical properties and attach therapeutics. Because of the repetitive nature of the ELP sequence, polymer size is particularly amenable to manipulation. ELP fusion proteins are being actively developed as therapeutics for many disease applications, and how the ELP size and shape affects its pharmacokinetics and biodistribution is a critical question for the general field of ELP drug delivery. To address this, we generated a library of ELPs ranging in size from 25 kDa to 110 kDa. Terminal plasma half-life was directly proportional to polymer size, and organ biodistribution was also size dependent. The kidneys accumulated the highest levels of ELP of all sizes, followed by the liver. Within the kidney, most ELP was found in the proximal tubule, but intra-renal localization shifted from exclusively cortical to a mixture of cortical and medullary as ELP size increased.
How do neuroleptics affect cognitive dysfunctions in schizophrenia? (1999)

In studies of how neuroleptics affect schizophrenia there has been a certain shift from symptoms to cognitive deficits. This paper is a review of effect studies, organized in accordance with six different areas of cognitive and psychophysiologic measures. The effects of both conventional neuroleptics and the newer antipsychotic medication are reviewed. Although many studies have been carried out, it is difficult to arrive at clear conclusions. There is not sufficient empirical evidence that traditional neuroleptics have dramatic effects on any of the cognitive functions examined. What can be said with certainty is that anticholinergic medication adversely affects memory and learning in patients with schizophrenia. Results from the few studies published so far indicate that the new generation of neuroleptics, primarily risperidone, has a more positive effect on cognitive functions than conventional neuroleptics.
Efficiency of Feed Use in Beef Cattle (1963)

Feed efficiency measured as a function of gain in body weight and feed consumed was studied for 1,324 bull and heifer calves at three experiment stations. Three measures were computed: (1) feed consumption adjusted for differences in gain; (2) gain adjusted for differences in feed consumption; and (3) the ratio of gain to feed consumed. In all three measures, mid-weight was considered simultaneously in an attempt to remove differences in maintenance requirements. Efficiency expressed as gain adjusted for differences in feed consumption (i.e., ±deviation from the regression of gain on consumption) was considered the most accurate mathematical description of the cause and effect relationships and resulted in the highest heritability of the three measures studied. No trends in the heritabilities calculated for each experiment station were noted. The combined heritabilities were 0.65 for gain on test, 0.64 for feed consumed, 0.62 for gain adjusted for differences in feed consumption, 0.28 for feed consumption adjusted for differences in gain, and 0.36 for the ratio of gain to feed consumed. A path analysis of feed efficiency (gain adjusted for feed consumption), feed consumption and gain was made. The analysis indicated that 38% of the variation in gain could be attributed directly to genetic differences in feed efficiency. Genetic differences in feed consumption accounted for 25% of the variation in gain. The remaining 37% of the variation in gain was accounted for by variations in environmental influences. The genetic correlation between feed efficiency and gain was 0.79, between feed consumption and gain was 0.64, and between feed efficiency and feed consumption was 0.04. These results indicate that selecting for gain should be effective and lead to both increased feed efficiency and increased feed consumption. Selecting for feed efficiency would increase feed efficiency and result in increased daily gain, but feed consumption would not be affected. Selection for feed consumption would increase feed consumption and daily gain, but would lead to no improvement in feed efficiency other than that attributable to a smaller portion of the intake being used for body maintenance.
Maintenance of sinus rhythm with metoprolol CR initiated before cardioversion and repeated cardioversion of atrial fibrillation: a randomized double-blind placebo-controlled study (2007)

A treatment strategy of metoprolol CR started before cardioversion in combination with prompt second cardioversion in case of early relapse (1-6 weeks) significantly increases the proportion of patients in SR during six months of follow-up.
Commissioning cost‐effective delivery of intravenous iron (2011)

Abstract In our Navigator series Omar Ali looks at some of the commissioning and medicines management issues facing primary and secondary care and provides guidance and solutions. Copyright © 2011 Wiley Interface Ltd
Activation of Monocyte/Macrophage Functions Related to Acute Atheroma Complication by Ligation of CD40 (1997)

By inducing the expression of matrix-degrading proteinases and of TF procoagulant, CD40 signaling may contribute to the triggering of acute coronary events.
Antiviral Screening of Multiple Compounds against Ebola Virus (2016)

In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine). A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna). The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.
A phase II study of active specific immunotherapy and5-FU/Leucovorin as adjuvant therapy for stage III colon carcinoma (2002)

Active specific immunotherapy, using vaccines with autologous tumour cells and BCG, significantly reduces the rate of tumour recurrence in stage II colon cancer patients, while no clinical benefit has yet been observed in stage III patients. Adjuvant treatment with 5-Fluorouracil/Leucovorin is now considered standard therapy for stage III colon carcinoma and results in an absolute survival benefit of approximately 10%. Yet, the 5-year overall survival rate of stage III colon cancer patients is only 40-50%. Combining chemotherapy and immunotherapy might improve prognosis for stage III patients, especially when considering that active specific immunotherapy and chemotherapy have shown synergistic effects in pre-clinical tumour models. We performed a phase II study with 56 patients, using the combination of active specific immunotherapy and chemotherapy as an adjuvant therapy in stage III colon cancer patients to assess the influence of 5-Fluorouracil/Leucovorin on anti-tumour immunity induced by autologous tumour cell vaccinations. Anti-tumour immunity was measured before and after chemotherapy by means of delayed type hypersensitivity reactions, taken 48 h after the third and the fourth vaccination. We also investigated the toxicity of this combined immuno-chemotherapy treatment. Delayed type hypersensitivity reactions before chemotherapy had a median size of 20.3 mm, while after chemotherapy delayed type hypersensitivity size was 18.4 mm (P=0.01), indicating that chemotherapy hardly affected anti-tumour immunity. The severity of ulcers at the BCG vaccination sites was comparable to previous studies. In 30% of the patients grade III or grade IV chemotherapy related toxicity was seen; this is comparable to what is normally observed after adjuvant chemotherapy alone. This study shows that the active specific immunotherapy-induced anti-tumour immune response is only minimally impaired by consecutive chemotherapy and that the combined treatment of stage III colon cancer patients with active specific immunotherapy and 5-Fluorouracil/Leucovorin does not cause unexpected toxicity.
Detection of breast cancer micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction. Comparison between MUC1 mRNA and keratin 19 mRNA amplification. (1996)

Usefulness of MUC1 mRNA and keratin 19 mRNA as a target of reverse-transcriptase polymerase chain reaction (RT-PCR) was compared in the detection of breast cancer micrometastases in axillary lymph nodes. RT-PCR amplification of MUC1 mRNA and keratin 19 mRNA was conducted using total RNA samples. RT-PCR products were stained with ethidium bromide and analyzed by agarose gel electrophoresis. Expression of both MUC1 mRNA and keratin 19 mRNA was detected by RT-PCR in a breast cancer cell line (MRK) and in all the 23 primary breast cancers but not in the control lymph nodes obtained from patients with benign diseases. A serial dilution study of MRK cells against normal lymph node cells has shown that detection sensitivity of MUC1 RT-PCR and keratin 19 RT-PCR were 1/10(5) and 1/10(6) (cancer/lymph node cells), respectively. Sixty-three axillary lymph nodes were obtained from 23 patients with primary breast cancer, and metastases in each lymph node were investigated by histological examination (hematoxylin and eosin sections) and RT-PCR method. In all 10 lymph nodes, which were histologically metastasis-positive, both MUC1 mRNA and keratin mRNA were detected by RT-PCR. Of the 53 histologically negative lymph nodes, 3 (6%) and 5 (9%) lymph nodes were found to express MUC1 mRNA and keratin 19 mRNA, respectively, indicating the presence of micrometastases which could be detected by RT-PCR but not by histological examination. These results demonstrate the usefulness of both MUC1 RT-PCR and keratin 19 RT-PCR in the detection of breast cancer micrometastases in lymph nodes, and also indicate the superiority of keratin 19 RT-PCR over MUC1 RT-PCR because of its higher detection sensitivity.
Down-regulation and Inactivation of Neutral Endopeptidase 24.11 (Enkephalinase) in Human Neutrophils (1989)

Neutral endopeptidase (EC 3.4.24.11, NEP) is an integral membrane protein of human neutrophils. NEP is identical with the common acute lymphoblastic leukemia antigen (CALLA) of leukemic cells. The expression of NEP on the surface of neutrophils is down-regulated by endocytosis which can be induced by phorbol 12-myristate 13-acetate (PMA) at 37 degrees C. The activity of the enzyme on the surface of intact cells decreases by 76% within 5 min. The activity can be recovered, however, if the cells are lysed within 5 min of the endocytosis. After 30 min, only 32% of the NEP activity is present in the neutrophil lysates. The loss of activity is presumably due to proteolytic inactivation. Diacylglycerol and monoclonal antibody to CALLA/NEP also induce internalization of NEP. PMA induces endocytosis even at 4 degrees C, but NEP is not inactivated at that temperature. The disappearance of NEP activity after adding PMA was inhibited by various agents. Among the most active were the phospholipase inhibitor 4-bromophenacyl bromide and a combination of the serine protease and cathepsin inhibitors, diisopropylfluorophosphate and N-ethylmaleimide. The employment of fluorescent monoclonal antibody confirmed the down-regulation and internalization of NEP antigen on the neutrophils. Since NEP inactivates chemotactic peptides and thereby affects chemotaxis of neutrophils (Painter, R. G., Dukes, R., Sullivan, J., Carter, R., Erdös, E. G., and Johnson, A. R. (1988) J. Biol. Chem. 263, 9456-9461), the down-regulation of NEP activity on the cell membrane may modulate the function of these cells in inflammation.
Cloning, sequencing, and molecular analysis of the sol operon of Clostridium acetobutylicum, a chromosomal locus involved in solventogenesis (1993)

A DNA region of Clostridium acetobutylicum contiguous with the adc operon has been cloned and sequenced. Structural genes encoding the acetoacetyl coenzyme A:acetate/butyrate:coenzyme A transferase (ctfB and ctfA) and an alcohol/aldehyde dehydrogenase (adhE) could be identified. These three genes together with a small open reading frame (ORF) of unknown function (upstream of adhE) formed an operon (sol operon), as shown by mRNA analyses. The complete sol operon was transcriptionally induced or derepressed before the onset of solventogenesis, thus confirming earlier results of Northern hybridizations with a ctfB gene probe (U. Gerischer and P. Dürre, J. Bacteriol. 174:426-433, 1992). Upstream of the sol operon, we identified two putative promoters that were located in regions with possible stem-loop structures formed by several inverted repeats. The distal promoter P1 showed only minor transcription initiation in solventogenic C. acetobutylicum cells but was recognized in Escherichia coli, presumably because of its high similarity to the sigma 70 consensus sequence. The adhE-proximal promoter P2 directed the major transcription start point in solventogenic C. acetobutylicum but was not recognized in E. coli. The clostridial AdhE showed high similarity to a novel family (type III) of alcohol dehydrogenases. Two other ORFs (ORF 5 and ORF 6) were found on the cloned DNA region that showed no significant similarity to sequences in various available data bases. mRNA studies revealed that ORF 5 formed a monocistronic operon and showed increased expression before onset of solventogenesis.
ChemInform Abstract: POSSIBLE ANTIPARKINSONIAN COMPOUNDS ‐ PART XII. SYNTHESIS OF SOME QUINAZOLONE DERIVATIVES (1978)

Abstract Die Anthranilsäuren (I) werden über die Benzoxazinone (II) in die Hydroxyethyl‐chinazolone (III) übergeführt.