gebhart/patrepeval huggingface dataset:
Aberrant expression of an amplified c-myb oncogene in two cell lines from a colon carcinoma. (1984)

Two cell lines (COLO 201 and COLO 205) derived independently from a single adenocarcinoma of the human colon each harbored an approximately 10-fold amplification of the cellular oncogene c-myb and a proportional abundance of the 4-kilobase mRNA derived from c-myb. By contrast, expression of c-myb could not be detected in cells from a variety of other solid tumors, including other colon carcinomas. Analysis of the amplified DNA with restriction endonucleases failed to reveal any topographical abnormalities within c-myb. Neither COLO 201 nor COLO 205 carry the double minute chromosomes and homogeneously staining regions of chromosomes that frequently serve as karyotypic signatures of amplified DNA. Instead, amplified c-myb is carried on what appear to be disomic or trisomic copies of the same anomalous marker chromosome that is characteristic of both COLO 201 and COLO 205. The karyological origin of this abnormal chromosome is not presently apparent. Our findings show c-myb expression by cells outside of the hemopoietic lineage, raise the possibility that amplification and/or ectopic expression of c-myb may have contributed to the genesis of the tumor from which the cells of COLO 201 and COLO 205 arose, and suggest that amplification of cellular oncogenes may be a more common factor in tumorigenesis than might have been suspected from available karyological data.
Screening Rose Clover and Subterranean Clover Germplasm for Isoflavones (1991)

Subterranean clovers ( Trifolium brachycalycinum Katzn. and Morley, T. subterraneum L., and T. yanninicum Katzn. &amp; Morley) contain phytoestrogenic isoflavones. High levels of these compounds are responsible for sheep ( Ovis aries ) reproductive disorders. Our objective was to screen the available subterranean and rose clover ( T. hirtum All.) germplasm from the USDA Plant Introduction collection for isoflavone content. Clover plants were grown in the greenhouse and sampled when the seedlings were 42‐d old. Leaves were extracted with methanol (7 d at 5 °C) and analyzed using highperformance liquid chromatography techniques. Isoflavones were very low (&lt;0.2 g kg −1 ) or not detectable in rose clover. Total isoflavone levels in subterranean clover ranged from 0.1 to 18.5 g kg −1 . The information generated in this study will aid in identification of subterranean clover lines with low isoflavone traits.
PEN110 treatment functionally inactivates the PBMNCs present in RBC units: comparison to the effects of exposure to gamma irradiation (2002)

Because PEN110 was as effective as gamma irradiation at inhibiting WBC proliferation, PEN110 treatment could potentially be used to prevent the development of GVHD following transfusion.
Automatic detection of instruments in laparoscopic images: a first step towards high level command of robotized endoscopic holders (2006)

The tracking of surgical instruments offers interesting possibilities for the development of high level commands for robotized camera holders in laparoscopic surgery. We present a new method to detect instruments in laparoscopic images which uses information on the 3D position of the insertion point of an instrument in the abdominal cavity. This information strongly constrains the search for the instrument in each endoscopic image. Hence, the instrument can be detected thanks to shape considerations, which would otherwise not be feasible in near real time. Early results show that the method is rapid and robust to partial occlusion and smoke
Wild-Type Human TDP-43 Expression Causes TDP-43 Phosphorylation, Mitochondrial Aggregation, Motor Deficits, and Early Mortality in Transgenic Mice (2010)

Transactivation response DNA-binding protein 43 (TDP-43) is a principal component of ubiquitinated inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions and in amyotrophic lateral sclerosis (ALS). Mutations in TARDBP, the gene encoding TDP-43, are associated with sporadic and familial ALS, yet multiple neurodegenerative diseases exhibit TDP-43 pathology without known TARDBP mutations. While TDP-43 has been ascribed a number of roles in normal biology, including mRNA splicing and transcription regulation, elucidating disease mechanisms associated with this protein is hindered by the lack of models to dissect such functions. We have generated transgenic (TDP-43PrP) mice expressing full-length human TDP-43 (hTDP-43) driven by the mouse prion promoter to provide a tool to analyze the role of wild-type hTDP-43 in the brain and spinal cord. Expression of hTDP-43 caused a dose-dependent downregulation of mouse TDP-43 RNA and protein. Moderate overexpression of hTDP-43 resulted in TDP-43 truncation, increased cytoplasmic and nuclear ubiquitin levels, and intranuclear and cytoplasmic aggregates that were immunopositive for phosphorylated TDP-43. Of note, abnormal juxtanuclear aggregates of mitochondria were observed, accompanied by enhanced levels of Fis1 and phosphorylated DLP1, key components of the mitochondrial fission machinery. Conversely, a marked reduction in mitofusin 1 expression, which plays an essential role in mitochondrial fusion, was observed in TDP-43PrP mice. Finally, TDP-43PrP mice showed reactive gliosis, axonal and myelin degeneration, gait abnormalities, and early lethality. This TDP-43 transgenic line provides a valuable tool for identifying potential roles of wild-type TDP-43 within the CNS and for studying TDP-43-associated neurotoxicity.
Loss of OPA1 Perturbates the Mitochondrial Inner Membrane Structure and Integrity, Leading to Cytochrome c Release and Apoptosis (2003)

OPA1 encodes a large GTPase related to dynamins, anchored to the mitochondrial cristae inner membrane, facing the intermembrane space. OPA1 haplo-insufficiency is responsible for the most common form of autosomal dominant optic atrophy (ADOA, MIM165500), a neuropathy resulting from degeneration of the retinal ganglion cells and optic nerve atrophy. Here we show that down-regulation of OPA1 in HeLa cells using specific small interfering RNA (siRNA) leads to fragmentation of the mitochondrial network concomitantly to the dissipation of the mitochondrial membrane potential and to a drastic disorganization of the cristae. These events are followed by cytochrome c release and caspase-dependent apoptotic nuclear events. Similarly, in NIH-OVCAR-3 cells, the OPA1 siRNA induces mitochondrial fragmentation and apoptosis, the latter being inhibited by Bcl2 overexpression. These results suggest that OPA1 is a major organizer of the mitochondrial inner membrane from which the maintenance of the cristae integrity depends. As loss of OPA1 commits cells to apoptosis without any other stimulus, we propose that OPA1 is involved in the cytochrome c sequestration and might be a target for mitochondrial apoptotic effectors. Our results also suggest that abnormal apoptosis is a possible pathophysiological process leading to the retinal ganglion cells degeneration in ADOA patients.
Noninvasive Measurement of Hematocrit by Electrical Admittance Plethysmography Technique (1980)

A new method for the noninvaive measurement of hematocrit by means of electrical admittance plethysmography was developed. The pninciple of this method is based on the evidence that the elecical admittance variation in a finger segment inmersed in an electrolyte solution disappears when the resistivity of the solution is equal to that of the blood flowing into the segment. Thus, the blood resistivity and, therefore, the hematocrit can be noninvasively determined from the electrolyte resistivity. The hematocrit values determined by this method (HctY) were compared with those by the capillary method (Hctc) in 16 subjects: the linear regression equation was HctY = 1.02Hctc-0.35 with a correlation coefficient r = 0.981.
Exopolysaccharide Production and Texture-Promoting Abilities of Mixed-Strain Starter Cultures in Yogurt Production (1997)

An exopolysaccharide-producing strain of Lactobacillus delbrueckii ssp. bulgaricus (CNRZ 1187) and two colonial white and pink variants were grown in skim milk in association with a strain of Streptococcus thermophilus (CNRZ 389) that did not produce exopolysaccharide to assess the effects of associative growth on exopolysaccharide formation. After 10 h of fermentation, viscosity (380 mPa.s) was highest with the parental strain CNRZ 1187 in the mixed-strain starter, the lowest (220 mPa.s) with the mixed-strain starter containing the white variant and S. thermophilus CNRZ 389, and intermediate (290 mPa.s) with the mixed-strain starter containing the pink variant and S. thermophilus CNRZ 389. Viscosities of the milks with exopolysaccharide-producing strains decreased after mechanical stirring, but values remained higher (170 to 230 mPa.s) than those obtained with nonproducing strains (70 mPa.s). The mixed-strain starter composed of the white colonies of L. delbrueckii spp. bulgaricus and S. thermophilus produced the highest amount of exopolysaccharide (240 mg/L), and the mixed-strain starter containing the parental strain CNRZ 1187 produced the lowest amount (110 mg/L) of exopolysaccharide. The exopolysaccharide production from the mixed-strain starter containing the white and pink L. delbrueckii ssp. bulgaricus colonies began earlier and was higher after 3 h of fermentation than that from the starter containing the parental L. delbrueckii ssp. bulgaricus strain. Production of exopolysaccharide from the latter approached the maximum in the beginning of the stationary growth phase; production from the mixed-strain starter with the pink and white variants continued during the early stationary growth phase. The exopolysaccharide contained mainly galactose with small amounts of glucose and rhamnose. The monosaccharide composition of the exopolysaccharide changed during the exponen-tial growth phase ( 6 h ) and remained stable thereafter.
Analysis of HLA class I expression in different metastases from two melanoma patients undergoing peptide immunotherapy (2001)

We characterized the HLA class I alterations in five metastases obtained from two patients with melanoma immunized with Melan A/MART-1, tyrosinase and gp100 tumor peptides. All three metastases analyzed in the first patient (NW145) showed a similar HLA class I alteration with a dual population of melanoma cells. One population was HLA class I antigen positive and the other had loss of heterozygosity (LOH) in the short arm of chromosome 6 leading to an HLA haplotype loss (A02011, B4007, Cw1). The absence of HLA-A2 antigen may explain why this patient did not develop HLA-A2 restricted, Melan A/MART-1 specificity immunization, since this HLA molecule is the restriction element for the tumor peptides used. However, this HLA-deficient population was not selected after peptide immunotherapy. The primary tumor in this patient presented LOH in region 6q, but only in the vertical growth phase of the lesion, whereas LOH at 6p was observed only in DNA from metastatic material. The second patient (NW16) also presented two metastatic lesions with an identical HLA molecular defect, i.e. HLA B locus downregulation (HLA B51011: serological B51; B1503: serological B70). One lesion expressed the tumor antigen (Melan A/ MART-1), but the other did not. Interestingly, the antigen-positive metastasis regressed after peptide immunotherapy, whereas the other progressed rapidly. These findings provide the first indication that multiple metastases generated in the same host can have identically altered HLA class I phenotypes.
[Post-operatory biometry and refraction results estimated and refraction surprises--clinical study]. (2003)

Preoperative biometry has a major influence on the success or failure of IOL implantation procedures. The paper wishes to demonstrate the significance of this manoeuvre for the refraction and visual outcome and for the postoperative satisfaction rate of the patients. The clinical study has rulled out for one year period and a number of 239 patients suffered a IOL implantation procedure (cataract or lens extraction for refractive purposes). The preoperative biometry was always necessary. We used one of the existing IOL power calculation formula (SRK II, SRK T, Holladay). The surgeon decided about the IOL power, always after discussing with the patient their postoperative refractive expectations. The postoperative refraction was, in the majority of cases, the estimated refraction and the errors were similar with those from the literature. Refractive surprises of several diopters were registered in high myopic and hyperopic eyes or in cases of coexisting ocular diseases which have modified the anatomical parameters of the eye. In conclusion, small errors in calculation can have large effects on visual outcome. This problem will be solved in the future, because the field is evolving rapidly driven by a new understanding of the anatomy of the eye and new hardware for measuring that anatomy.
Speeding up artificial neural networks in the 'real' world (1989)

Summary form only given, as follows. A novel heuristic, called focused-attention backpropagation (FAB) learning, is introduced. FAB enhances the backpropagation procedure by focusing attention on the exemplar patterns that are most difficult to learn. Results are reported using FAB learning to train multilayer feedforward artificial neural networks to represent real-valued elementary functions. The rate of learning observed for FAB is 1.5 to 10 times faster than for backpropagation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
P‐Glycoprotein‐Mediated Hoechst 33342 Transport Out of the Lipid Bilayer (1997)

High-level expression of P-glycoprotein, a 170-kDa mammalian plasma membrane ATPase, is the cause of an important and widespread form of cancer multidrug resistance. P-glycoprotein reduces cellular accumulation of an enormous variety of lipophilic compounds. The basis for this broad substrate specificity is not well understood. We explored this issue by measuring the kinetics of transport of the lipophilic P-glycoprotein substrate Hoechst 33342 by P-glycoprotein-rich plasma membrane vesicles from CH(R)B30 cells. Hoechst 33342 is fluorescent when bound to the membrane, but not when in the aqueous medium, allowing movement of the dye out of the membrane to be quantitated by fluorescence intensity. The initial specific rate of transport was directly proportional to the amount of Hoechst 33342 in the lipid phase and inversely proportional to the concentration in the aqueous phase. This demonstrates that P-glycoprotein removes Hoechst 33342 from the lipid membrane, where it concentrates due to its hydrophobicity. Because the membrane concentration of hydrophobic P-glycoprotein substrates is high, it may be that P-glycoprotein need not recognize them with high affinity. Transport of hydrophobic substrates out of the lipid bilayer instead of the cytoplasm thus helps to explain the broad substrate specificity of P-glycoprotein.
Acid–base catalysis in Leuconostoc mesenteroides sucrose phosphorylase probed by site-directed mutagenesis and detailed kinetic comparison of wild-type and Glu237→Gln mutant enzymes (2007)

The role of acid-base catalysis in the two-step enzymatic mechanism of alpha-retaining glucosyl transfer by Leuconostoc mesenteroides sucrose phosphorylase has been examined through site-directed replacement of the putative catalytic Glu237 and detailed comparison of purified wild-type and Glu237-->Gln mutant enzymes using steady-state kinetics. Reactions with substrates requiring Brønsted catalytic assistance for glucosylation or deglucosylation were selectively slowed at the respective step, about 10(5)-fold, in E237Q. Azide, acetate and formate but not halides restored catalytic activity up to 300-fold in E237Q under conditions in which the deglucosylation step was rate-determining, and promoted production of the corresponding alpha-glucosides. In situ proton NMR studies of the chemical rescue of E237Q by acetate and formate revealed that enzymatically formed alpha-glucose 1-esters decomposed spontaneously via acyl group migration and hydrolysis. Using pH profiles of kcat/K(m), the pH dependences of kinetically isolated glucosylation and deglucosylation steps were analysed for wild-type and E237Q. Glucosylation of the wild-type proceeded optimally above and below apparent pK(a) values of about 5.6 and 7.2 respectively whereas deglucosylation was dependent on the apparent single ionization of a group of pK(a) approximately 5.8 that must be deprotonated for reaction. Glucosylation of E237Q was slowed below apparent pK(a) approximately 6.0 but had lost the high pH dependence of the wild-type. Deglucosylation of E237Q was pH-independent. The results allow unequivocal assignment of Glu237 as the catalytic acid-base of sucrose phosphorylase. They support a mechanism in which the pK(a) of Glu237 cycles between approximately 7.2 in free enzyme and approximately 5.8 in glucosyl enzyme intermediate, ensuring optimal participation of the glutamate residue side chain at each step in catalysis. Enzyme deglucosylation to an anionic nucleophile took place with Glu237 protonated or unprotonated. The results delineate how conserved active-site groups of retaining glycoside hydrolases can accommodate enzymatic function of a phosphorylase.
74. A rearrangement of carbamyl-sulphones and -sulphides (1936)

W. J. Evans and S. Smiles, J. Chem. Soc., 1936, 329 DOI: 10.1039/JR9360000329
Soluble Guanylate Cyclase Stimulation Prevents Fibrotic Tissue Remodeling and Improves Survival in Salt-Sensitive Dahl Rats (2011)

Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions.
Molecular Interactions of Antibody Drugs Targeting PD-1, PD-L1, and CTLA-4 in Immuno-Oncology (2019)

Cancer cells can evade immune surveillance through the molecular interactions of immune checkpoint proteins, including programmed death 1 (PD-1), PD-L1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Since 2011, the FDA-approved antibody drugs ipilimumab (Yervoy<sup>®</sup>), nivolumab (Opdivo<sup>®</sup>), pembrolizumab (Keytruda<sup>®</sup>), cemiplimab (Libtayo<sup>®</sup>), atezolizumab (Tecentriq<sup>®</sup>), durvalumab (Imfinzi<sup>®</sup>), and avelumab (Bavencio<sup>®</sup>), which block the immune checkpoint proteins, have brought about a significant breakthrough in the treatment of a wide range of cancers, as they can induce durable therapeutic responses. In recent years, crystal structures of the antibodies against PD-1, PD-L1, and CTLA-4 have been reported. In this review, we describe the latest structural studies of these monoclonal antibodies and their interactions with the immune checkpoint proteins. A comprehensive analysis of the interactions of these immune checkpoint blockers can provide a better understanding of their therapeutic mechanisms of action. The accumulation of these structural studies would provide a basis that is essential for the rational design of next-generation therapies in immuno-oncology.
Synthetic approaches towards new polymer systems by the combination of living carbocationic and anionic polymerizations (1996)

Abstract This study summarizes recent efforts to obtain by combination of living carbocationic and anionic polymerizations block copolymers which are potential precursors for building new well‐defined polymeric architectures with microphase separated morphology. Living carbocationic polymerization (LCCP) yields telechelic polyisobutylene (PIB) chains with a variety of useful endgroups, such as tert ‐chlorine, isopropenyl, primary hydroxyl, tolyl etc. When tolyl‐ended PIB was used as precursor for macroinitiator of living anionic polymerization of 2‐( tert ‐butyldimethylsilyloxy)ethyl methacrylate ( t BuMe 2 SiOEMA), mixtures of homopolymers and block copolymers were formed due to incomplete lithiation of this chain end. In another approach a new functionalization method was developed by end‐quenching living PIB chains with 1,1‐diphenylethylene (DPE). In the presence of BCl 3 a new telechelic PIB with 2,2‐diphenylvinyl (DPV) endgroups was formed. A corresponding DPV model compound was synthesized from 2‐chloro‐2,4,4‐trimethylpentane (TMPCl). Because of steric hindrance less than quantitative lithiation of this material occurred. Controlled deprotection of P t BuMe 2 SiOEMA obtained by living anionic polymerization (LAP) was utilized to prepare a precursor network composed of partially deprotected P t BuM 2 SiOEMA and hydroxyl‐telechelic PIB by using a diisocyanate crosslinker. After network formation deprotection with HCl was completed and a new amphiphilic network (APN) containing PIB and poly(2‐hydroxyethyl) methacrylate) (PHEMA) segments crosslinked by urethane linkages was obtained.
Precolumn Reactions with Electrophoretic Analysis Integrated on a Microchip (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPrecolumn Reactions with Electrophoretic Analysis Integrated on a MicrochipStephen C. Jacobson, Roland. Hergenroder, Alvin W. Jr. Moore, and J. Michael. RamseyCite this: Anal. Chem. 1994, 66, 23, 4127–4132Publication Date (Print):December 1, 1994Publication History Published online1 May 2002Published inissue 1 December 1994https://pubs.acs.org/doi/10.1021/ac00095a003https://doi.org/10.1021/ac00095a003research-articleACS PublicationsRequest reuse permissionsArticle Views646Altmetric-Citations214LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Rapid Ventricular Pacing Produces Myocardial Protection by Nonischemic Activation of K ATP + Channels (1996)

Rapid ventricular pacing protects the myocardium against infarction via nonischemic KATP+ channel activation. Continued activation of KATP+ channels does not appear mandatory for the protection that is still present 15 minutes after cessation of pacing.