gebhart/patrepeval huggingface dataset:
Endogenous Retrotransposition Activates Oncogenic Pathways in Hepatocellular Carcinoma (2013)

LINE-1 (L1) retrotransposons are mobile genetic elements comprising ~17% of the human genome. New L1 insertions can profoundly alter gene function and cause disease, though their significance in cancer remains unclear. Here, we applied enhanced retrotransposon capture sequencing (RC-seq) to 19 hepatocellular carcinoma (HCC) genomes and elucidated two archetypal L1-mediated mechanisms enabling tumorigenesis. In the first example, 4/19 (21.1%) donors presented germline retrotransposition events in the tumor suppressor mutated in colorectal cancers (MCC). MCC expression was ablated in each case, enabling oncogenic β-catenin/Wnt signaling. In the second example, suppression of tumorigenicity 18 (ST18) was activated by a tumor-specific L1 insertion. Experimental assays confirmed that the L1 interrupted a negative feedback loop by blocking ST18 repression of its enhancer. ST18 was also frequently amplified in HCC nodules from Mdr2(-/-) mice, supporting its assignment as a candidate liver oncogene. These proof-of-principle results substantiate L1-mediated retrotransposition as an important etiological factor in HCC.
Preservation of DNA (2007)

The preservation of DNA is of wide interest to scientists in disparate fields from biorepository management to pharmaceutical sciences. Although the term “preservation” is used by all these fields and refers to the maintenance of chemical and physical integrity of the DNA molecule, it should not be surprising that the perspectives of scientists from these distinct fields differ significantly. Most notably, the time frame for stability of a pharmaceutical product is approximately 2 years, whereas meaningful stability for an evolutionary biologist is measured in the hundreds of millions of years. Such divergent viewpoints not only have a significant effect on the time span of preservation, but also on what criteria are used to assess “stability.” This review discusses the literature addressing the maintenance of DNA integrity from the perspective of developing methods that offer improved preservation. Specifically, studies on the stability of DNA in solution, frozen, and dried are discussed. The findings from these studies are compared, and the costs associated with maintaining DNA samples via contemporary methods (i.e., cold storage) are estimated. In light of the significant cost of maintaining samples in the frozen state, we conclude that dry storage at ambient temperatures would be adequate for many applications, and we suggest preservation strategies that should be investigated based on findings in the literature. In addition, we offer suggestions regarding critical studies that could be performed to compare published results from different fields using vastly different criteria to assess “stability.”
The Safety and Efficacy of Seasonale, a Novel 91-Day Extended Oral Contraceptive Regimen* (2002)

Eastern Virginia Medical School, Norfolk, VA *This document includes a discussion of use of a product that is unapproved by the U.S. Food and Drug Administration.
Layout tool for high speed electronic and optical circuits (1990)

Powerful layout editing systems are available nowadays for designing integrated circuits, specially in the more popular MOS technology. At present, gallium arsenide, silicon-bipolar, integrated and holographic optics are starting to emerge as potential technologies for designing VLSI circuits. Their use will certainly require a review on the concepts of layout tools, and new algorithms may be included in such systems. This is particularly true for the design of holographic optical interconnection, which is promising way of bringing optics into electronic circuits in order to alleviate the present VLSI communication problems. An algorithm for holographic optical interconnection is discussed for this application it is important that the data structure can represent curved shapes. A comer-stitching based data structure that can represent rectangles, trapezoid and curved shapes is discussed.
Sustained intraocular VEGF neutralization results in retinal neurodegeneration in the Ins2Akita diabetic mouse (2015)

Current therapies that target vascular endothelial growth factor (VEGF) have become a mainstream therapy for the management of diabetic macular oedema. The treatment involves monthly repeated intravitreal injections of VEGF inhibitors. VEGF is an important growth factor for many retinal cells, including different types of neurons. In this study, we investigated the adverse effect of multiple intravitreal anti-VEGF injections (200 ng/μl/eye anti-mouse VEGF164, once every 2 weeks totalling 5-6 injections) to retinal neurons in Ins2(Akita) diabetic mice. Funduscopic examination revealed the development of cotton wool spot-like lesions in anti-VEGF treated Ins2(Akita) mice after 5 injections. Histological investigation showed focal swellings of retinal nerve fibres with neurofilament disruption. Furthermore, anti-VEGF-treated Ins2(Akita) mice exhibited impaired electroretinographic responses, characterized by reduced scotopic a- and b-wave and oscillatory potentials. Immunofluorescent staining revealed impairment of photoreceptors, disruptions of synaptic structures and loss of amacrine and retinal ganglion cells in anti-VEGF treated Ins2(Akita) mice. Anti-VEGF-treated WT mice also presented mild amacrine and ganglion cell death, but no overt abnormalities in photoreceptors and synaptic structures. At the vascular level, exacerbated albumin leakage was observed in anti-VEGF injected diabetic mice. Our results suggest that sustained intraocular VEGF neutralization induces retinal neurodegeneration and vascular damage in the diabetic eye.
Compound developmental eye disorders following inactivation of TGFβ signaling in neural-crest stem cells (2005)

In the developing eye the lens acts as a TGFbeta signaling center that controls the development of eye structures derived from the NC. Defective TGFbeta signal transduction interferes with NC-cell differentiation and survival anterior to the lens and with normal tissue morphogenesis and patterning posterior to the lens. The similarity to developmental eye disorders in humans suggests that defective TGFbeta signal modulation in ocular NC derivatives contributes to the pathophysiology of these diseases.
Influence of timing of gain on growth and reproductive performance of beef replacement heifers. (1997)

Our objective was to determine whether beef heifers could be developed by delaying the majority of weight gain until the last third of the developmental period before the onset of the breeding season. Spring-born Angus x Hereford heifers were used in each of two consecutive years and were allotted at weaning to gain either .45 kg/d for the entire developmental period (yr 1 = 159 d, n = 40; yr 2 = 168 d, n = 40; EVENGAIN) or to gain .11 kg/d from d 0 to 112, followed by .91 kg/d from d 112 to 159 (yr 1, n = 40) or d 168 (yr 2, n = 40; LATEGAIN). Body weights and condition scores were determined at d 0, 112, and 159 (yr 1) or d 0, 112, and 168 (yr 2). Heifers were subjected to a 60-d breeding season. Frame scores and pelvic areas were determined at the conclusion of the breeding season. Actual daily gains for EVENGAIN heifers for yr 1 and yr 2 were .60 and .51 kg/d, respectively. LATEGAIN heifers gained .25 and .05 kg/d during the restricted phases from d 0 to 112, followed by 1.14 and 1.32 kg/d during the accelerated growth phases for yr 1 and 2, respectively. Body weight at the onset of the breeding season and weight at puberty were not different between treatments in either year. Age at puberty did not differ in yr 1, but, age at puberty in yr 2 was delayed (P < .01) in LATEGAIN (406.9 d) compared to EVENGAIN (386.3 d) heifers. The LATEGAIN and EVENGAIN heifers had similar pelvic areas, frame scores, and body condition scores in each year. First-service conception rates of both groups were similar in yr 1 (55.5 vs 55.3%). In yr 2, LATEGAIN heifers tended (P = .18) to have an increase in first-service conception rate compared to EVENGAIN heifers (71.1 vs 56.4%). No treatment differences occurred in either average age of conception or overall pregnancy rates at the conclusion of the breeding season for either year. The LATEGAIN heifers were developed to a similar BW on 12 (P < .01) and 2.5% (not statistically significant) less feed for yr 1 and 2, respectively, compared to EVENGAIN heifers. We interpret these data to indicate that delaying the majority of weight gain until late in heifer development may decrease costs without detrimental effects on reproductive performance.
Effect of Attachment Site on Stability of Cleavable Antibody Drug Conjugates (2015)

The systemic stability of the antibody–drug linker is crucial for delivery of an intact antibody–drug conjugate (ADC) to target-expressing tumors. Linkers stable in circulation but readily processed in the target cell are necessary for both safety and potency of the delivered conjugate. Here, we report a range of stabilities for an auristatin-based payload site-specifically attached through a cleavable valine-citrulline-p-aminobenzylcarbamate (VC-PABC) linker across various sites on an antibody. We demonstrate that the conjugation site plays an important role in determining VC-PABC linker stability in mouse plasma, and that the stability of the linker positively correlates with ADC cytotoxic potency both in vitro and in vivo. Furthermore, we show that the VC-PABC cleavage in mouse plasma is not mediated by Cathepsin B, the protease thought to be primarily responsible for linker processing in the lysosomal degradation pathway. Although the VC-PABC cleavage is not detected in primate plasma in vitro, linker stabilization in the mouse is an essential prerequisite for designing successful efficacy and safety studies in rodents during preclinical stages of ADC programs. The divergence of linker metabolism in mouse plasma and its intracellular cleavage offers an opportunity for linker optimization in the circulation without compromising its efficient payload release in the target cell.
A Phase I Study of 17-Allylamino-17-Demethoxygeldanamycin Combined with Paclitaxel in Patients with Advanced Solid Malignancies (2008)

The recommended phase II dose of twice-weekly 17-AAG (175 mg/m2) and weekly paclitaxel (80 mg/m2/wk) was tolerated well. There was no evidence of drug-drug pharmacokinetic interactions.
Relationships between musical structure and psychophysiological measures of emotion. (2007)

Psychophysiological studies with music have not examined what exactly in the music might be responsible for the observed physiological phenomena. The authors explored the relationships between 11 structural features of 16 musical excerpts and both self-reports of felt pleasantness and arousal and different physiological measures (respiration, skin conductance, heart rate). Overall, the relationships between musical features and experienced emotions corresponded well with those known between musical structure and perceived emotions. This suggests that the internal structure of the music played a primary role in the induction of the emotions in comparison to extramusical factors. Mode, harmonic complexity, and rhythmic articulation best differentiated between negative and positive valence, whereas tempo, accentuation, and rhythmic articulation best discriminated high arousal from low arousal. Tempo, accentuation, and rhythmic articulation were the features that most strongly correlated with physiological measures. Music that induced faster breathing and higher minute ventilation, skin conductance, and heart rate was fast, accentuated, and staccato. This finding corroborates the contention that rhythmic aspects are the major determinants of physiological responses to music.
A Multi-Scale Model of Hepcidin Promoter Regulation Reveals Factors Controlling Systemic Iron Homeostasis (2014)

Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how BMP6 and IL6 control hepcidin expression. Transcription factor (TF) phosphorylation and reporter gene expression were measured under co-stimulation conditions, and the promoter was perturbed by mutagenesis. Using mathematical modeling, we systematically analyzed potential mechanisms of cooperative and competitive promoter regulation by the transcription factors, and experimentally validated the model predictions. Our results reveal that hepcidin cross-regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signaling crosstalk is insignificant. We find that the presence of two BMP-responsive elements enhances the steepness of the promoter response towards the iron-sensing BMP signaling axis, which promotes iron homeostasis in vivo. IL6 co-stimulation reduces the promoter sensitivity towards the BMP signal, because the SMAD and STAT transcription factors compete for recruiting RNA polymerase to the transcription start site. This may explain why inflammatory signals disturb iron homeostasis in anemia of inflammation. Taken together, our results reveal why the iron homeostasis circuit is sensitive to perturbations implicated in disease.
Mesenchymal stem cells and insulin‐like growth factor‐I gene‐enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons (2009)

Tendinitis remains a catastrophic injury among athletes. Mesenchymal stem cells (MSCs) have recently been investigated for use in the treatment of tendinitis. Previous work has demonstrated the value of insulin-like growth factor-I (IGF-I) to stimulate cellular proliferation and tendon fiber deposition in the core lesion of tendinitis. This study examined the effects of MSCs, as well as IGF-I gene-enhanced MSCs (AdIGF-MSCs) on tendon healing in vivo. Collagenase-induced bilateral tendinitis lesions were created in equine flexor digitorum superficialis tendons (SDFT). Tendons were treated with 10 x 10(6) MSCs or 10 x 10(6) AdIGF-MSCs. Control limbs were injected with 1 mL of phosphate-buffered saline (PBS). Ultrasound examinations were performed at t = 0, 2, 4, 6, and 8 weeks. Horses were euthanized at 8 weeks and SDFTs were mechanically tested to failure and evaluated for biochemical composition and histologic characteristics. Expression of collagen types I and III, IGF-I, cartilage oligomeric matrix protein (COMP), matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), and aggrecanase-1 (ADAMTS-4) were similar in MSC and control tendons. Both MSC and AdIGF-MSC injection resulted in significantly improved tendon histological scores. These findings indicate a benefit to the use of MSCs and AdIGF-MSCs for the treatment of tendinitis.
Relationships Between Structural Parameters and Tenacity of Polypropylene Monofilaments (1965)

Quantitative relationships have been established between the tensile strength of polypropylene fibers and their molecular weight, molecular-weight distribution, crystal linity, and orientation. An equation describing the combined effects of the structural parameters on the strength of the fibers has been derived. The correlation shows that, with polypropylene fibers of 94% to 98% isotacticity, the strength of the fibers is primarily a function of the orientation and that the contribution of the other parameters is small in comparison.
Transgenic weed beets: possible, probable, avoidable? (2002)

Summary Weed beets pose a serious problem for sugar beet Beta vulgaris crops. Traditionally, the only efficient method of weed control has been manual removal, but the introduction of transgenic herbicide‐tolerant sugar beets may provide an alternative solution because non‐tolerant weed beets can be destroyed by herbicide. We evaluated the possibility that new, transgenic, weed beets may arise by gene flow between wild and crop plants. In a study area in northern France, weed beets were present in variable densities in sugar beet fields of up to 80 weed beet plants m −2 . Weed beets arise from a long‐lived seed bank, with seeds germinating from depths of 5 cm or less. In addition, diploid F 1 crop–wild hybrids and triploid variety bolters (individuals with a low vernalization requirement) were present in low densities in virtually all sugar beet fields. We found gene flow to be possible between all forms, illustrated by both overlapping flowering periods in the field and successful controlled cross‐pollinations. The F 1 crop–wild hybrids result from pollination in the seed‐production region by wild plants possessing the dominant bolting allele B for flowering without experiencing a period of cold. In the case of a transgene for herbicide tolerance incorporated into male‐sterile seed‐bearer plants, such hybrids will contain both the herbicide‐tolerance and the bolting allele. Contamination of the fields by transgenic weed beets will be the result unless bolters are removed manually. The same will apply in the case of a cytoplasmically inherited transgene. Incorporation of the transgene into the pollinator plants will prevent the immediate formation of transgenic weed beets. However, in sugar beet fields, variety bolters may successfully cross‐pollinate with weed beets in neighbouring fields. The use of diploid pollinator plants instead of tetraploids will considerably enhance gene flow towards wild beets, and is not, therefore, an attractive option. In conclusion, the appearance of transgenic weed beets is possible but can best be retarded if the transgene for herbicide tolerance is incorporated into the tetraploid pollinator breeding line.
Specific flavonoids stimulate intercellular colonization of non-legumes by Azorhizobium caulinodans (1996)

International audience
Comprehensive organometallic chemistry III (2007)

VOLUME 1 Fundamentals (G. Parkin). VOLUME 2 Compounds of Groups 1 to 2 and 11 to 12 (K. Meyer). VOLUME 3 Compounds of Groups 13 to 15 (C.E. Housecroft). VOLUME 4 Compounds of Groups 3 to 4 and the f elements (M. Bochmann). VOLUME 5 Compounds of Groups 5 to 7 (K.H. Theopold). VOLUME 6 Compounds of Group 8 (M.I. Bruce). VOLUME 7 Compounds of Group 9 (C. Claver). VOLUME 8 Compounds of Group 10 (A. Canty). VOLUME 9 Applications I: Main Group Compounds in Organic Synthesis (P. Knochel). VOLUME 10 Applications II: Transition Metal Compounds in Organic Synthesis 1 (Iwao Ojima, Tamejiro Hiyama). VOLUME 11 Applications II: Transition Metal Compounds in Organic Synthesis 2 (Tamejiro Hiyama, Iwao Ojima). VOLUME 12 Applications III: Functional Materials, Environmental and Biological Applications (D. O'Hare). VOLUME 13 Cumulative Indexes
6,7-Dihydro-2-benzothiophen-4(5<i>H</i>)-ones:  A Novel Class of GABA-A α5 Receptor Inverse Agonists (2002)

Nonselective inverse agonists at the benzodiazepine binding site on the GABA-A chloride ion channel enhance cognitive performance in animals but cannot be used in the treatment of cognitive disorders because of anxiogenic and convulsant side effects. We have identified a novel series of GABA-A alpha5 receptor ligands during our search for alpha5 receptor inverse agonists as potential cognition enhancers. In particular, 6,6-dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one (26) has been identified as a functionally selective GABA-A alpha5 inverse agonist.
Analysis on electromechanical coupling coefficients in AlN-based bulk acoustic wave resonators based on first-principle calculations (2012)

We discuss the effect of aluminum nitride (AlN) film stress on the electromechanical coupling coefficient (k <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ) of film bulk acoustic resonators (FBAR) based on first-principle calculations and experiments. Our calculations indicate that the compressive stress of AlN film induces the expansion of the c-axis lattice constant and affected the piezoelectric constant of AlN. We found that the piezoelectric constant of AlN and k <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> of FBAR estimated using first-principle calculation increase with decreasing compressive stress of AlN films. We also confirmed from experiments that the piezoelectric constant increased from 6.5 to 7.1pC/N due to the decrease in compressive stress. Finally, we fabricated air-gap type FBAR that have different AlN film stresses. As a result, k <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> improved from 6.0 to 6.5% by controlling the film stress from -1200 to 0MPa.
Necrotizing Effects of Staphylococcus aureus Extract on Mouse Sarcoma 180. (1961)

1) A trichloracetic acid extract of Staphylococcus aureus, strain D (5 to 40 μg/mouse), in 24 hours caused extensive hemorrhagic necrosis of Sarcoma 180 in HaICR Swiss mice when injected intraperi-toneally 7 days after tumor implantation. The extract was ineffective against tumors 1 to 4 days after implantation. 2) The effect was also produced in Sarcoma 180 grown in C57B1/6, C3H, AKR and DBA2 mice. 3) Epinephrine, dibenzyline and the antihistaminic drug Benadryl, in the doses used, did not alter the necrotizing activity of the extract. Cortisone, however, reduced the incidence of the effect.
Saturated and epimorphically closed varieties of semigroups (1984)

Abstract We establish a necessary condition ( E ) for a semigroup variety to be closed under the taking of epimorphisms and a necessary condition ( S ) for a variety to consist entirely of saturated semigroups. Condition ( S ) is shown to be sufficient for heterotypical varieties and a stronger condition ( S ′) is shown to be sufficient for homotypical varieties.
Cystobactamids: Myxobacterial Topoisomerase Inhibitors Exhibiting Potent Antibacterial Activity (2014)

The development of new antibiotics faces a severe crisis inter alia owing to a lack of innovative chemical scaffolds with activities against Gram-negative and multiresistant pathogens. Herein, we report highly potent novel antibacterial compounds, the myxobacteria-derived cystobactamids 1-3, which were isolated from Cystobacter sp. and show minimum inhibitory concentrations in the low μg mL(-1) range. We describe the isolation and structure elucidation of three congeners as well as the identification and annotation of their biosynthetic gene cluster. By studying the self-resistance mechanism in the natural producer organism, the molecular targets were identified as bacterial type IIa topoisomerases. As quinolones are largely exhausted as a template for new type II topoisomerase inhibitors, the cystobactamids offer exciting alternatives to generate novel antibiotics using medicinal chemistry and biosynthetic engineering.
Optimizing Parameters for Terminating Cortical Afterdischarges with Pulse Stimulation (2002)

BPS is more likely to terminate ADs at primary electrodes, if given early, if applied to the negative peak of the AD waveform, if AD has a rhythmic pattern, and if AD did not start immediately after LS.