gebhart/patrepeval huggingface dataset:
The Arp2/3 complex mediates multigeneration dendritic protrusions for efficient 3‐dimensional cancer cell migration (2013)

Arp2/3 is a protein complex that nucleates actin filament assembly in the lamellipodium in adherent cells crawling on planar 2-dimensional (2D) substrates. However, in physiopathological situations, cell migration typically occurs within a 3-dimensional (3D) environment, and little is known about the role of Arp2/3 and associated proteins in 3D cell migration. Using time resolved live-cell imaging and HT1080, a fibrosarcoma cell line commonly used to study cell migration, we find that the Arp2/3 complex and associated proteins N-WASP, WAVE1, cortactin, and Cdc42 regulate 3D cell migration. We report that this regulation is caused by formation of multigeneration dendritic protrusions, which mediate traction forces on the surrounding matrix and effective cell migration. The primary protrusions emanating directly from the cell body and prolonging the nucleus forms independent of Arp2/3 and dependent on focal adhesion proteins FAK, talin, and p130Cas. The Arp2/3 complex, N-WASP, WAVE1, cortactin, and Cdc42 regulate the secondary protrusions branching off from the primary protrusions. In 3D matrices, fibrosarcoma cells as well as migrating breast, pancreatic, and prostate cancer cells do not display lamellipodial structures. This study characterizes the unique topology of protrusions made by cells in a 3D matrix and show that these dendritic protrusions play a critical role in 3D cell motility and matrix deformation. The relative contribution of these proteins to 3D migration is significantly different from their role in 2D migration.
miR-221 Silencing Blocks Hepatocellular Carcinoma and Promotes Survival (2011)

Patients with advanced hepatocellular carcinoma (HCC) face a dismal prognosis because of a lack of any effective therapies. To address this situation, we conducted a preclinical investigation of the therapeutic efficacy of oligonucleotides directed against the oncogenic microRNA miR-221, which has been implicated in HCC. Of 9 chemistries evaluated, we determined that a 2'-O-methyl phosphorothioate-modified anti-miR-221 oligonucleotide was most effective at reducing proliferation in vitro. A cholesterol-modified isoform of anti-miR-221 (chol-anti-miR-221) exhibited improved pharmacokinetics and liver tissue distribution compared with unmodified oligonucleotide. Chol-anti-miR-221 significantly reduced miR-221 levels in liver within a week of intravenous administration and in situ hybridization studies confirmed accumulation of the oligonucleotide in tumor cells in vivo. Within the same period, chol-anti-miR-221 reduced tumor cell proliferation and increased markers of apoptosis and cell-cycle arrest, elevating the tumor doubling time and increasing mouse survival. Taken together, our findings offer a preclinical proof of efficacy for chol-anti-miR-221 in a valid orthotopic mouse model of HCC, suggesting that this targeted agent could benefit treatment for patients with advanced HCC.
The recA gene from Clostridium perfringens is induced by methyl methanesulphonate and contains an upstream Cheo box (1997)

The recA gene from Clostridium perfringens was cloned using degenerate oligonucleotide primers designed from conserved regions of RecA proteins from other bacteria. The 1089 bp gene encoded a putative RecA protein with 69% amino acid sequence similarity to the RecA protein from Bacillus subtilis. The C. perfringens recA gene was induced by exposure to methyl methanesulphonate and complemented a recA mutant of Escherichia coli. A cheo box was identified in the region upstream of the gene. Since this SOS-like operator site is conserved in many DNA-damage-inducible recA gene regions from Gram-positive bacteria, the results suggest that the regulation of the C. perfringens recA gene also involves the binding of a LexA-like protein to this site.
A common protein binds to two silencers 5′ to the human β-globin gene (1989)

The temporal sequence of expression of human globin genes during development suggests precise regulation of these genes. Recent studies have characterized a number of DNA sequences within or flanking the human beta-globin gene which are important in its regulation and several proteins which bind to these sequences have been identified. We have found two proteins which bind 5' to the human beta-globin gene. One of these proteins, which we designate BP1, binds to two sequences, one between -550 and -527 bp relative to the cap site, the other between -302 and -294 bp. A second protein, BP2, binds to sequences between -275 and -263 bp. The binding sites for both BP1 and BP2 are in two regions which function as silencers in a transient expression assay using the human erythroleukemia cell line K562. These results and others presented here suggest that BP1 may act as a repressor protein. Negative regulation seems to be an important component of tissue and developmental specific globin gene regulation.
Segregated Coupling of Phospholipases A2, Cyclooxygenases, and Terminal Prostanoid Synthases in Different Phases of Prostanoid Biosynthesis in Rat Peritoneal Macrophages (1998)

We examined herein the functional linkage of enzymes regulating the initial, intermediate, and terminal steps of PG biosynthesis to provide PGs in rat peritoneal macrophages stimulated with LPS and/or A23187. Quiescent cells stimulated with A23187 produced thromboxane B2 (TXB2) in marked preference to PGE2 within 30 to 60 min (constitutive immediate response), which was mediated by preexisting cytosolic phospholipase A2 (cPLA2), cyclooxygenase-1 (COX-1), and TX synthase. Cells treated with LPS predominantly produced PGE2 during culture for 3 to 24 h (delayed response), where cPLA2 and secretory PLA2 functioned cooperatively with inducible COX-2, which was, in turn, coupled with inducible PGE2 synthase. Cells primed for 12 h with LPS and stimulated for 30 min with A23187 produced PGE2 in marked preference to TXB2 (induced immediate response), in which three inducible enzymes, cPLA2, COX-2, and PGE2 synthase, were functionally linked. Preferred coupling of the two inducible enzymes, COX-2 and PGE2 synthase, was further confirmed by the ability of LPS-treated cells to convert exogenous arachidonic acid to PGE2 optimally at a time when both enzymes were simultaneously induced. These results suggest that distinct PG biosynthetic enzymes display segregated functional coupling following different transmembrane stimulation events even when enzymes that catalyze similar reactions in vitro coexist in the same cells.
Isothermal Titration Calorimetry (2004)

In the last two decades, isothermal titration calorimetry (ITC) has become the preferred technique to determine the binding energetics of biological processes, including protein-ligand binding, protein-protein binding, DNA-protein binding, protein-carbohydrate binding, protein-lipid binding, and antigen-antibody binding. In this unit several protocols are presented, ranging from the basic ones that are aimed at characterizing binding of moderate affinity to advanced protocols that are aimed at determining very high or very low affinity binding processes. Also, alternate protocols for special cases (homodimeric proteins and unstable proteins) and additional information accessible by ITC (heat capacity and protonation/deprotonation processes coupled to binding) are presented.
The Value of Serum Prostate Specific Antigen Determinations Before and after Radical Prostatectomy (1989)

We evaluated serum prostate specific antigen before and after radical prostatectomy. In 100 consecutive patients who underwent radical prostatectomy, preoperative prostate specific antigen levels tended to increase with the increasing severity of pathological stage. However, even at levels of greater than 10 ng. per ml. the positive and negative predictive values (78 and 61 per cent, respectively) of prostate specific antigen to predict extracapsular disease were not sufficient to make this test useful alone for staging. In theory, after radical prostatectomy prostate specific antigen should be zero if no remaining prostatic tissue is present. Tests of precision and analytical sensitivity in our laboratory using a commercial prostate specific antigen assay revealed that a value of 0.4 ng. per ml. or more is different from zero at a greater than 95 per cent confidence level. With this guideline we evaluated the meaning of prostate specific antigen levels 3 to 6 months after radical prostatectomy in 59 men. Among men whose prostate specific antigen level was less than 0.4 ng. per ml. only 9 per cent demonstrated recurrence as evidenced by the development of positive bone scan or progressively elevated prostate specific antigen levels within 6 to 50 months. Alternatively, in men whose 3 to 6-month prostate specific antigen level was 0.4 ng per ml. or more there was evidence of recurrence in 100 per cent within 6 to 49 months (p less than 0.0001). Progressively elevated (more than 0.4 ng. per ml.) prostate specific antigen levels preceded recurrence from 12 to 43 months in all 6 patients who had positive bone scans, while increasing prostate specific antigen levels since radical prostatectomy have continued from 9 to 65 months in the 11 patients who have no radiological evidence of recurrent disease to date. Prostatic acid phosphatase serum values after radical prostatectomy were not useful to predict persistent disease. Prostate specific antigen values 3 to 6 months after radical prostatectomy are a sensitive indicator of persistent disease after radical prostatectomy and often precede other evidence of this occurrence by many years. This fact may alter concepts about surgical results, and possibly shorten and sharpen clinical studies involving adjuvant therapy after radical prostatectomy.
Extension of Life-Span by Introduction of Telomerase into Normal Human Cells (1998)

Normal human cells undergo a finite number of cell divisions and ultimately enter a nondividing state called replicative senescence. It has been proposed that telomere shortening is the molecular clock that triggers senescence. To test this hypothesis, two telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected with vectors encoding the human telomerase catalytic subunit. In contrast to telomerase-negative control clones, which exhibited telomere shortening and senescence, telomerase-expressing clones had elongated telomeres, divided vigorously, and showed reduced straining for beta-galactosidase, a biomarker for senescence. Notably, the telomerase-expressing clones have a normal karyotype and have already exceeded their normal life-span by at least 20 doublings, thus establishing a causal relationship between telomere shortening and in vitro cellular senescence. The ability to maintain normal human cells in a phenotypically youthful state could have important applications in research and medicine.
BREAST AND ARTIFICIAL FEEDING (1934)

There is no question that the artificial feeding of infants has taken remarkable strides in the past few years. It has had such success that in the minds of many physicians and perhaps a large proportion of the public there has grown up the idea that artificial formulas can safely replace breast milk without any detrimental results to the child. So far as we know, this has been based on empirical observations and has not been supported by sufficient evidence to be regarded as in any way proof. Although in the past few years many accessory foodstuffs have unquestionably been discovered, notably vitamins, which are necessary for life, and it has been discovered also that in many instances the inorganic materials were of far greater importance than had been suspected, one cannot be at all certain that all the elements which go to make up a perfect food have been
Levitation in Physics (1989)

Several physical effects allow free floatation of solid and even liquid matter. Materials may be levitated by a jet of gas, by intense sound waves, or by beams of laser light. In addition, conductors levitate in strong radio-frequency fields, charged particles in alternating electric fields, and magnets above superconductors or vice versa. Although levitation by means of ferromagnets is unstable, supper-conductors may be suspended both above and below a magnet as a result of flux pinning. Levitation is used for containerless processing and investigation of materials, for frictionless bearings and high-speed ground transportation, for spectroscopy of single atoms and microparticles, and for demonstrating superconductivity in the new oxide superconductors.
Fluorescence in situ hybridization (FISH) : protocols and applications (2010)

The design simplicity and cost-effectiveness of the early Fluorescence in situ Hybridization (FISH) protocols, combined with the significant acceleration of discoveries in related technical areas like fluorescence microscopy, digital imaging, and nucleic acid technology have prompted the diversification of the original technique into an outstanding number of imaginative and useful applications, thus promoting its expansion into different areas of basic and applied research in the post-genomic era. In Fluorescence in situ Hybridization (FISH): Protocols and Applications, experts in the field portray the vibrant complexity and diversity of the current FISH protocol landscape, providing cutting-edge examples of various applications for genetic and developmental research, cancer research, reproductive medicine, diagnostic and prognostic purposes, microbial ecology and evolutionary studies. The book is divided into four convenient sections covering the core techniques, technical advancements and novel adaptations, applications for human genetics and medicine, as well as protocols for model organisms. Written in the highly successful Methods in Molecular Biology™ series format, chapters include introductions to their respective chapters, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes highlighting tips on troubleshooting and avoiding known pitfalls. Comprehensive and up-to-date, Fluorescence in situ Hybridization (FISH): Protocols and Applications aims to aid scientists from across the world in applying this tried-and-true scientific technique to their own lab’s current research
Formation of extremely low resistance Ti/Pt/Au ohmic contacts to p-GaAs (1993)

Nonalloyed Ti/Pt/Au contacts to heavily doped p-GaAs have been fabricated using effective cleaning of the semiconductor surface by bombardment with low energy Ar+ ions (60 eV) prior to the metal deposition. Short-time annealing cycles for 1 and 20 s were employed in order to restore the primary properties of the subsurface layer disordered during ion bombardment. Annealing at temperatures ranging from 420 to 530 °C provides formation of contacts with an extremely low resistivity of 2.8×10−8 Ω cm2. A definite correlation between electrical properties and structural modifications of the contact interface was found. Measurements of the contact resistivity at different ambient temperatures yielded a good quantitative agreement with the theoretically predicted values using the field-emission model. The results indicate that the metal-semiconductor junctions formed under optimal conditions are intimate and that tunneling is the dominant mechanism of the current flow.
Synthesis, Structure, and Biological Activity of New Azine‐Bridged Dinuclear Platinum(II) Complexes − a New Class of Anticancer Compounds (2003)

Abstract A recently described new class of dinuclear platinum anticancer compounds, represented so far by the isomeric azine‐bridged complexes [{ cis ‐Pt(NH 3 ) 2 Cl} 2 (µ‐pzn)]Cl 2 ( 1 ) (pzn = pyrazine), [{ cis ‐Pt(NH 3 ) 2 Cl} 2 (µ‐pmn)]Cl 2 ( 2 ) (pmn = pyrimidine) and [{ cis ‐Pt(NH 3 ) 2 Cl} 2 (µ‐pdn)](NO 3 ) 2 ( 3 ) (pdn = pyridazine), has been added to. Three new dinuclear complexes of this type, [{ cis ‐Pt(NH 3 ) 2 Cl} 2 (µ‐2,5pzn)]Cl 2 ( 4 ) (2,5pzn = 2,5‐dimethylpyrazine), [{ cis ‐Pt(NH 3 ) 2 Cl} 2 (µ‐qzn)]Cl 2 ( 5 ) (qzn = quinazoline), and [{ cis ‐Pt(NH 3 ) 2 Cl} 2 (µ‐pht)](NO 3 ) 2 ( 6 ) (pht = phthalazine), have been newly synthesized and characterized by 1 H and 195 Pt NMR spectroscopy. The interaction of the new compounds with 2 equiv. of 9EtG in D 2 O at 310 K has been investigated. Complexes 4 and 5 undergo substitution of both chloride ligands by 9EtG similarly to the related complexes 1 and 2 , respectively. The methyl substituents on the pyrazine ring induce steric hindrance in 4 resulting in a slower reaction rate as compared to 1 . Similarly to the case of 3 , interaction of complex 6 with 9EtG results in cleavage of the Pt−N(pht) bond and subsequent formation of the polymeric species. A cytotoxicity assay of 4 − 6 has been performed on seven human tumor cell lines and on L1210 murine leukemia cell lines, sensitive and resistant to cisplatin. Compounds 4 and 5 exhibit lower cytotoxicity than the analogous complexes with unsubstituted azines. Complex 6 is more active: its cytotoxicity in the L1210 cell lines is similar to that of cisplatin. Analysis of nuclear DNA fragmentation in L1210 cells treated with the azine‐bridged complexes 1 − 6 has been carried out. The results clearly indicate induction of apoptosis by all the compounds, implying considerable anticancer potential. The structure‐activity relationship for this class of dinuclear platinum( II ) complexes is discussed. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)
The dynamics of a family’s gut microbiota reveal variations on a theme (2014)

This analysis underscores the complex interactions that give rise to a personalized microbiota and suggests the value of studying families as a surrogate for longitudinal studies.
Experiments in automatic statistical thesaurus construction (1992)

A well constructed thesaurus has long been recognized as a valuable tool in the effective operation of an information retrieval system. This paper reports the results of experiments designed to determine the validity of an approach to the automatic construction of global thesauri (described originally by Crouch in [1] and [2] based on a clustering of the document collection. The authors validate the approach by showing that the use of thesauri generated by this method results in substantial improvements in retrieval effectiveness in four test collections. The term discrimination value theory, used in the thesaurus generation algorithm to determine a term's membership in a particular thesaurus class, is found not to be useful in distinguishing a “good” from an “indifferent” or “poor” thesaurus class). In conclusion, the authors suggest an alternate approach to automatic thesaurus construction which greatly simplifies the work of producing viable thesaurus classes. Experimental results show that the alternate approach described herein in some cases produces thesauri which are comparable in retrieval effectiveness to those produced by the first method at much lower cost.
Synthesis of Anacardic Acids, 6-[8(Z),11(Z)-Pentadecadienyl]salicylic Acid and 6-[8(Z),11(Z),14-Pentadecatrienyl]salicylic Acid. (2001)

11-Chloro-3-methoxy-2-undecenal was synthesized from 8-bromooctanol, and an annelation reaction with this aldehyde and ethyl acetoacetate proceeded to give the ethyl 6-(8-chlorooctyl)salicylate. Ethyl 6-(8-chlorooctyl)salicylate was converted to ethyl 6-(7-formylheptyl)-2-methoxybenzoate through the iodide after protection of the phenolic hydroxyl group. Finally, the Wittig reaction with the aldehyde and triphenylphosphonium iodides in the presence of BuLi gave the methoxybenzoates, and then treatments of these methoxybenzoates with BBr3 in CH2Cl2 and 10% NaOH in ethanol gave 6-18(Z),11(Z)-pentadecadienyllsalicylic acid (anacardic acid 3) and 6-[8(Z),11(Z),14-pentadecatrienyl]salicylic acid (anacardic acid 4) which were isolated from plants of the anacardiaceae.
Emergence and persistence of Pseudomonas aeruginosa in the cystic fibrosis airway. (1992)

Colonization in the respiratory tracts of cystic fibrosis (CF) patients by mucoid Pseudomonas aeruginosa correlates with the progression of bronchial airway pathology. There is a direct correlation between the incidence of Pseudomonas colonization and age, clinical score, extent of pulmonary disease, severity of radiographic changes, and level of serum immunoglobulins. The central propensity to Pseudomonas colonization in patients with CF is not freely understood, but we discuss the acquisition and persistence of P aeruginosa in the CF airway. Elucidation of pathogenetic mechanisms of CF inflammatory airways disease is the first essential step to initiating novel therapies. It has been difficult to prove that the ability of P aeruginosa to adhere to the respiratory epithelium and provide selective advantage for this gram-negative bacillus over other potential pathogens for infection in the CF airway. However, flexible filaments (pili) extending from the Pseudomonas cell wall are thought to medicate epithelial cell adherence for nonmucoid P aeruginosa, and similarly, the gelatinous exopolysaccharide alginate produced by mucoid variants of P aeruginosa seems to be the adhesive to tracheal cells. Following the signal event of adherence, this bacterial pathogen competes successfully for iron cofactor and multiplies, releasing proteases with broad substrate specificities that dramatically alter the airway antiprotease screen, and the pathogen creates defects in local antibacterial defenses. Lung inflammation in CF is characterized by massive neutrophil infiltration. Although critical to host defense, neutrophils also cause progressive airway damage by release of bioactive lipids, oxygen metabolites, and granule enzymes such as hydrolases, myeloperoxidase (MPO), lysozyme, and neutral serine proteases. The necessarily circumscribed discussion that follows will focus narrowly on the host cell-derived factors (macrophages and neutrophils) proposed as important components in this pathogenetic scheme.
Protein kinase Cdc15 activates the Dbf2-Mob1 kinase complex (2001)

Exit from mitosis in budding yeast requires inactivation of cyclin-dependent kinases through mechanisms triggered by the protein phosphatase Cdc14. Cdc14 activity, in turn, is regulated by a group of proteins, the mitotic exit network (MEN), which includes Lte1, Tem1, Cdc5, Cdc15, Dbf2/Dbf20, and Mob1. The direct biochemical interactions between the components of the MEN remain largely unresolved. Here, we investigate the mechanisms that underlie activation of the protein kinase Dbf2. Dbf2 kinase activity depended on Tem1, Cdc15, and Mob1 in vivo. In vitro, recombinant protein kinase Cdc15 activated recombinant Dbf2, but only when Dbf2 was bound to Mob1. Conserved phosphorylation sites Ser-374 and Thr-544 (present in the human, Caenorhabditis elegans, and Drosophila melanogaster relatives of Dbf2) were required for DBF2 function in vivo, and activation of Dbf2-Mob1 by Cdc15 in vitro. Although Cdc15 phosphorylated Dbf2, Dbf2-Mob1, and Dbf2(S374A/T544A)-Mob1, the pattern of phosphate incorporation into Dbf2 was substantially altered by either the S374A T544A mutations or omission of Mob1. Thus, Cdc15 promotes the exit from mitosis by directly switching on the kinase activity of Dbf2. We propose that Mob1 promotes this activation process by enabling Cdc15 to phosphorylate the critical Ser-374 and Thr-544 phosphoacceptor sites of Dbf2.