gebhart/patrepeval huggingface dataset:
Ribonuclease H1-dependent hepatotoxicity caused by locked nucleic acid-modified gapmer antisense oligonucleotides (2016)

Gapmer antisense oligonucleotides cleave target RNA effectively in vivo, and is considered as promising therapeutics. Especially, gapmers modified with locked nucleic acid (LNA) shows potent knockdown activity; however, they also cause hepatotoxic side effects. For developing safe and effective gapmer drugs, a deeper understanding of the mechanisms of hepatotoxicity is required. Here, we investigated the cause of hepatotoxicity derived from LNA-modified gapmers. Chemical modification of gapmer's gap region completely suppressed both knockdown activity and hepatotoxicity, indicating that the root cause of hepatotoxicity is related to intracellular gapmer activity. Gene silencing of hepatic ribonuclease H1 (RNaseH1), which catalyses gapmer-mediated RNA knockdown, strongly supressed hepatotoxic effects. Small interfering RNA (siRNA)-mediated knockdown of a target mRNA did not result in any hepatotoxic effects, while the gapmer targeting the same position on mRNA as does the siRNA showed acute toxicity. Microarray analysis revealed that several pre-mRNAs containing a sequence similar to the gapmer target were also knocked down. These results suggest that hepatotoxicity of LNA gapmer is caused by RNAseH1 activity, presumably because of off-target cleavage of RNAs inside nuclei.
Apparatus for Monitoring the Mineralization of Volatile <sup>14</sup> C-Labeled Compounds (1979)

Quantitative mineralization studies on radiolabeled compounds having high vapor pressures need to cope with several technical difficulties. An incubation and trapping system is described that was successfully used in mineralization studies on highly volatile trichlorobenzenes and other xenobiotic pollutants.
The Efficacy and Safety of <i>Tanacetum Parthenium</i> (Feverfew) in Migraine Prophylaxis—a Double-Blind, Multicentre, Randomized Placebo-Controlled Dose-Response Study (2002)

Tanacetum parthenium (feverfew), is a well-known herb for the prophylactic treatment of migraine. The primary objective was to show a dose-response of a new stable extract (MIG-99) reproducibly manufactured with supercritical CO2 from feverfew (T. parthenium). Furthermore, the study should provide data on the safety and tolerability of MIG-99. In a randomized, double-blind, multicentre, controlled trial with an adaptive design, the clinical efficacy and safety of three dosages of MIG-99 (2.08 mg; 6.25 mg; 18.75 mg t.i.d.) were compared with placebo. The patients (n = 147) suffered from migraine with and without aura according to International Headache Society (IHS) criteria and were treated with one of the study medications for 12 weeks after a 4-week baseline period. The primary efficacy parameter was the number of migraine attacks during the last 28 days of the treatment period compared with baseline. Secondary endpoints were total and average duration and intensity of migraine attacks, mean duration of the single attack, number of days with accompanying migraine symptoms, number of days with inability to work due to migraine as well as type and amount of additionally taken medications for the treatment of migraine attacks. The design of the study included a pre-planned adaptive interim analysis for patients with at least four migraine attacks within the baseline period. With respect to the primary and secondary efficacy parameter, a statistically significant difference was not found between the overall and the confirmatory intention-to-treat (ITT) sample in the exploratorily analysed four treatment groups. The frequency of migraine attacks for the predefined confirmatory subgroup of patients (n = 49) with at least four migraine attacks during the baseline period decreased in a dose-dependent manner (P = 0.001). The highest absolute change of migraine attacks was observed under treatment with 6.25 mg t.i.d. (mean +/- SD = -1.8 +/- 1.5 per 28 days) compared with placebo (-0.3 +/- 1.9; P = 0.02). Overall, 52 of 147 (35%) patients reported at least one adverse event (AE). The incidence of AEs in the active treatment groups was similar to that in the placebo group, and no dose-related effect was observed in any safety parameter. MIG-99 failed to show a significant migraine prophylactic effect in general. Accordingly, in the ITT analysis a dose-response relationship could not be observed. MIG-99 was shown to be effective only in a small predefined subgroup of patients with at least four attacks during the 28-day baseline period where the most favourable benefit-risk ratio was observed with a dosage of three capsules of 6.25 mg MIG-99 extract per day. Because of the low number of patients, these findings need to be verified in a larger sample. The incidence of AEs was similar for all treatment groups.
EXAFS and WAXS structure determination for an antiarthritic drug, sodium gold(I) thiomalate (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEXAFS and WAXS structure determination for an antiarthritic drug, sodium gold(I) thiomalateR. C. Elder, K. Ludwig, J. N. Cooper, and M. K. EidsnessCite this: J. Am. Chem. Soc. 1985, 107, 17, 5024–5025Publication Date (Print):August 1, 1985Publication History Published online1 May 2002Published inissue 1 August 1985https://doi.org/10.1021/ja00303a049RIGHTS & PERMISSIONSArticle Views210Altmetric-Citations65LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (220 KB) Get e-Alerts Get e-Alerts
Drug delivery systems for cancer drugs (2003)

Drug delivery systems can offer significant advantages in cancer therapy. They not only allow the delivery of active drug substances that are difficult to formulate (overcoming inherent shortcomings of both biologicals and sparingly water-soluble active drugs) but also decrease the inherent toxicity of most agents, increasing their efficacy (by modulation of the release kinetic from the formulation and of the residence time in the body) and specifically localising the therapy to the site of action. Due to the vast number of feasible approaches and the scrutiny they are under to achieve the abovementioned targets, it is obvious that this review cannot be exhaustive but instead will concentrate on highlighting recent progress in areas where the authors have seen growing interest for oncology applications. The main topics discussed will be oral delivery (with particular regard to advantages in modulating transporter inhibitors), loco-regional therapies (where the major focus will be on lung cancer therapy), colloidal delivery systems (liposomes and second generation lipid formulations) and biodegradable implants.
Efficacy and safety of autologous hematopoietic stem cell therapy for refractory Crohn's disease (2017)

Autologous HSCT could be a complicated treatment with relatively high mortality and significantly high efficacy for refractory CD, which should be used with caution. However, more RCTs of larger samples using refined and standardized protocols and longer period of follow-up time are needed to further assess the outcomes of autologous HSCT therapy.
Functional Roles of Ubiquitin-Like Domain (ULD) and Ubiquitin-Binding Domain (UBD) Containing Proteins (2009)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTFunctional Roles of Ubiquitin-Like Domain (ULD) and Ubiquitin-Binding Domain (UBD) Containing ProteinsCaroline Grabbe† and Ivan Dikic*‡§†View Author Information Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University Frankfurt am Main, Theodor-Stern-Kai 7, D-60590 Frankfurt (Main), Germany, Mediterranean Institute for Life Sciences, 21000 Split, Croatia, and Department of Immunology, School of Medicine, University of Split, Soltanska 2, 21 000 Split, Croatia* To whom correspondence should be addressed. Phone: +49 69 6301 83647. Fax: +49 69 6301 5577. E-mail: [email protected]†Goethe University Frankfurt am Main.‡Mediterranean Institute for Life Sciences.§University of Split.Cite this: Chem. Rev. 2009, 109, 4, 1481–1494Publication Date (Web):March 2, 2009Publication History Received13 June 2008Published online2 March 2009Published inissue 8 April 2009https://doi.org/10.1021/cr800413pCopyright © 2009 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views5539Altmetric-Citations86LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (2 MB) Get e-AlertsSUBJECTS:Degradation,Fungi,Peptides and proteins,Surface interactions,Targeting Get e-Alerts
Drug therapy: dose‐response relationship of oral mesalazine in inflammatory bowel disease (1998)

Mesalazine is widely used in the treatment of inflammatory bowel disease. Little is known about the dose-response relationship and about possible dose related side effects. In ulcerative colitis higher dosages of mesalazine (3 g) are more effective in maintaining a remission than lower dosages (1.5 g). In mild to moderately active ulcerative colitis, studies also indicate that higher dosages might be more effective in inducing remission. Dose-comparing studies in Crohn's disease are even more sparse, but the available results indicate higher efficacy at higher dose levels. None of the known side effects of mesalazine are clearly dose-related. A pH-dependent release system, however, can cause a sudden release of high doses of mesalazine. Consequent peak levels in serum have been implicated in mesalazine induced nephrotoxicity. In conclusion, despite the current practice of using increasing dosages of mesalazine in inflammatory bowel disease, both efficacy and safety have been established tentatively.
[Anti-inflammatory and antipyretic activity of aqua-dihydroxybenzoate copper complexes]. (1992)

Using screening methods, the anti-inflammatory and antipyretic activities of mononuclear otahedral complexes [composition:Cu(2,YDHB)2.H2O;dihydroxybenzoate ion - DHB; Y(n)-4(8).5(4) and 6(8)] and the corresponding carboxylic acids were studied. On paw dextran edema (rats, an effective dose of 10 mg/kg), a higher efficacy of the complexes was found as compared with the acids. All compounds significantly reduced the endotoxin pyretic reaction (rabbits, in a single dose of 20 mg/kg; in the case of the first two complexes half-dose was administered). Marked toxic effects were determined for Cu(II) salts when they were administered i.p. The observed biological activities of complexes are discussed in relation to their proposed structures.
A crucial role for the phosphorylation of STRAP at Ser<sup>188</sup>by MPK38 in STRAP-dependent cell death through ASK1, TGF-β, p53, and PI3K/PDK1 signaling pathways (2014)

Serine-threonine kinase receptor-associated protein (STRAP) is a TGF-β receptor-interacting protein that participates in the regulation of cell proliferation and cell death in response to various stresses. Here, we demonstrate that STRAP phosphorylation plays an important role in determining the pro- or anti-apoptotic function of STRAP. Murine protein serine/threonine kinase 38 (MPK38) phosphorylates STRAP at Ser(188) via direct interaction. Complex formation between STRAP and MPK38 is mediated by Cys(152) and Cys(270) of STRAP and Cys(339) and Cys(377) of MPK38, suggesting the redox dependency of this interaction. MPK38-mediated STRAP Ser(188) phosphorylation contributes to the pro-apoptotic function of STRAP by modulating key steps in STRAP-dependent ASK1, TGF-β, p53, and PI3K/PDK1 signaling pathways. Moreover, knockdown of endogenous MPK38 using an inducible MPK38 shRNA system and in vivo activation of MPK38 by treatment of HEK293 and STRAP-null MEF cells with 1-chloro-2,4-dinitrobenzene (DNCB), a specific inhibitor of Trx reductase, provide evidence that STRAP Ser(188) phosphorylation plays a key role in STRAP-dependent cell death. Adenoviral delivery of MPK38 in mice also demonstrates that STRAP Ser(188) phosphorylation in the liver is tightly associated with cell death and proliferation through ASK1, TGF-β, p53, and PI3K/PDK1 pathways, resulting in apoptotic cell death.
Electroacoustic effect in electrolytes (1994)

A highly sensitive pulse-modulated technique has been used to verify experimentally the existence of electroacoustic effect in electrolytes. Some insight to the mechanisms involved is obtained by studying the Fourier spectrum of the detected acoustic signal and its dependence on the exciting voltage.
The Impact of Saponins or Saponin-Containing Plant Materials on Ruminant ProductionA Review (2005)

Saponins are steroid or triterpene glycoside compounds found in a variety of plants. Some saponin-containing plants, mainly legumes, have been used as animal feed, but others are toxic. Several studies on the effect of saponins on ruminant production have also been reported. Some in vitro and in vivo experiments that demonstrate the beneficial effects of saponin such as defaunation of the rumen and manipulation of the end products of fermentation are described. Defaunation is the selective removal of protozoa from the rumen microbial ecosystem by a cell membrane cholesterol-saponin interaction, which causes cell rupture. Because protozoa in the rumen cause protein turnover by predating on bacteria, defaunation increases the nitrogen utilization of the ruminant and may lead to an increase in growth, milk, or wool production. The growth-promoting effect was evident in the high roughage diet suggesting that the application of saponins or saponin-containing plant materials may be beneficial for the subsistence farmers in developing countries. Saponins are deglycosylated by rumen microbes. Some sapogenins have been detected in the digestive tract of ruminants; however, the direct action of these compounds on the host animal is still unclear. No information on the effects of saponin on ruminant reproduction is available. There is an urgent need for a systematic evaluation of the most active structural components of the saponins, and their interaction with the microbial community, the host animal, and the diet. Along with these studies, the direct effects of saponins or their microbial degradation products on the host must be examined in order to get the full understanding of the metabolism and beneficial effects of saponins on animals.
Novel Complication of an Emerging Disease: Invasive Klebsiella pneumoniae Liver Abscess Syndrome as a Cause of Acute Respiratory Distress Syndrome (2018)

Klebsiella pneumoniae is an increasingly recognized cause of a unique invasive syndrome manifesting as pyogenic liver abscess and hematogenous extrahepatic dissemination to a variety of sites, including the lung. Originally described only in Asia, this entity has now been reported across continents and ethnicities. Intrathoracic complications of invasive Klebsiella pneumoniae liver abscess syndrome (IKPLAS) have been characterized sporadically but have not been the subject of an all-encompassing investigation. Review of the English-language literature yields no reports of the acute respiratory distress syndrome as a consequence of IKPLAS. Herein we report what, to our knowledge, is the first such description.
移动系统存储文件（夹）菜鸟也行 (2004)

50期特别刊大家感觉怎么样？还喜欢吧，那些可都是众小编们优中选优之后的杰作啊，当然，本期也绝对不是“残羹冷炙”之作……不知道大家发现没有，“冲浪技巧”栏目新增加了一个“狂卿E夜”子栏目，怎么样，所有的聊天方面技巧都集中到此，大家感觉很爽吧？如果大家对这个新开设的栏目有什么意见或者建议的话，欢迎给泡泡鱼来信，最后，感谢大家对泡泡鱼的支持……
Microscale oscillating crack propagation in silicon nitride thin films (2010)

Controlled microscale (&lt;50 μm) wavy cracks in silicon nitride thin films have been produced through a simple heating process. The crack paths were controlled by metal patterns under the silicon nitride thin films. Wavy crack characteristics were investigated by changing the metal, metal linewidths, metal thickness, and silicon nitride thickness. We discuss the differences in the characteristics and mechanisms of propagation of wavy cracks formed due to differential thermal expansion and those that result from thermal gradients.
Adults with dyslexia exhibit large effects of crowding, increased dependence on cues, and detrimental effects of distractors in visual search tasks (2011)

Difficulties in visual attention are increasingly being linked to dyslexia. To date, the majority of studies have inferred functionality of attention from response times to stimuli presented for an indefinite duration. However, in paradigms that use reaction times to investigate the ability to orient attention, a delayed reaction time could also indicate difficulties in signal enhancement or noise exclusion once oriented. Thus, in order to investigate attention modulation and visual crowding effects in dyslexia, this study measured stimulus discrimination accuracy to rapidly presented displays. Adults with dyslexia (AwD) and controls discriminated the orientation of a target in an array of different numbers of - and differently spaced - vertically orientated distractors. Results showed that AwD: were disproportionately impacted by (i) close spacing and (ii) increased numbers of stimuli, (iii) did use pre-cues to modulate attention, but (iv) used cues less successfully to counter effects of increasing numbers of distractors. A greater dependence on pre-cues, larger effects of crowding and the impact of increased numbers of distractors all correlated significantly with measures of literacy. These findings extend previous studies of visual crowding of letters in dyslexia to non-complex stimuli. Overall, AwD do not use cues less, but they do use cues less successfully. We conclude that visual attention is an important factor to consider in the aetiology of dyslexia. The results challenge existing theoretical accounts of visual attention deficits, which alone are unable to comprehensively explain the pattern of findings demonstrated here.
[Assessment of the maximum allowable discharge of hazardous substances into the atmosphere with regard to population morbidity]. (1992)

Positive correlation between the data of the children morbidity and the air pollution was obtained. Mathematical models may be used in the forecast of medico-social effects of the air pollution and prevention of it.
Copper supplementation and the maintenance of bone mineral density in middle-aged women (1996)

Osteoporosis is a common disease of older women in developed countries. Hormone replacement therapy (HRT) is currently the most effective way of reducing the rate of bone loss in older women. This study investigated the effects of copper supplementation over 2 years on vertebral trabecular bone mineral density (VTBMD) of a group of 73 apparently healthy women, aged 45–56 years, recruited from a general practice in north Belfast. Women were given, at random and double blind, either a supplement of 3 mg copper as amino acid chelate or a placebo to take daily. At the beginning and end of the study, VTBMD of the lumbar vertebrae (L2–4) was measured by computed tomography-scan (CT-scan) and random blood samples were taken for putative measures of copper status (erythrocyte Cu and superoxide dismutase activity). The women were seen every 3 months to monitor compliance with supplementation. There was no difference in initial and final VTBMD for the 24 women who took the copper supplement (initial VTBMD 124.6 (32.1) mg/cm3 and final VTBMD 123.8 (36.3) mg/cm3) while the 32 women who took the placebo had significantly lower VTBMD at the end of the study period (initial VTBMD 120.7 (29.2) mg/cm3 and final VTBMD 113.2 (26.6) mg/cm3, paired t-test P = 0.01). Seventeen women (14 allocated the copper supplement and three the placebo) stopped taking the supplement during the study. Although copper supplementation had no effect on the putative biochemical measurements of copper status, it appeared to have reduced the loss of VTBMD in these middle-aged women over a 2 year period. © 1997 Wiley-Liss, Inc.
Identification and characterization of a soluble c-kit receptor produced by human hematopoietic cell lines (1995)

Stem cell factor (SCF) triggers cell growth by binding to cell surface c-kit receptors. Soluble forms of several cytokine receptors have been described and may play a role in the modulation of cytokine activity in vivo. For these reasons, we investigated whether human hematopoietic cells produce soluble c-kit receptors. The human leukemia cell lines OCIM1 and MO7e display approximately 80,000 and approximately 35,000 high-affinity cell surface c-kit receptors, respectively. Soluble c-kit receptors were detected by enzyme immunoassay in OCIM1 and MO7e culture supernatants. We determined the molecular weight and binding affinity of soluble c-kit receptor produced by OCIM1 cells, soluble c-kit receptor purified from human serum, and recombinant soluble c-kit receptor expressed in CHO cells. The three soluble c-kit receptors each have a molecular weight of 98 kD. Quantitative binding experiments with 125I-SCF indicate that the soluble c-kit receptors obtained from human serum or OCIM1 cells have binding affinities for SCF of approximately 200 to 300 pmol/L, in contrast to the recombinant form, which has a binding affinity of approximately 1.5 nmol/L. All three forms of the soluble c-kit receptor were able to compete with c-kit receptors on OCIM1 cells for 125I-SCF binding. Thus human hematopoietic cells can produce a soluble form of the c-kit receptor that retains high-affinity SCF binding activity. We speculate that the soluble c-kit receptor may bind SCF and function as a receptor antagonist in vivo.