gebhart/patrepeval huggingface dataset:
Myosin regulatory light chains are required to maintain the stability of myosin II and cellular integrity (2011)

Myosin II is an actin-binding protein composed of MHC (myosin heavy chain) IIs, RLCs (regulatory light chains) and ELCs (essential light chains). Myosin II expressed in non-muscle tissues plays a central role in cell adhesion, migration and division. The regulation of myosin II activity is known to involve the phosphorylation of RLCs, which increases the Mg2+-ATPase activity of MHC IIs. However, less is known about the details of RLC-MHC II interaction or the loss-of-function phenotypes of non-muscle RLCs in mammalian cells. In the present paper, we investigate three highly conserved non-muscle RLCs of the mouse: MYL (myosin light chain) 12A (referred to as MYL12A), MYL12B and MYL9 (MYL12A/12B/9). Proteomic analysis showed that all three are associated with the MHCs MYH9 (NMHC IIA) and MYH10 (NMHC IIB), as well as the ELC MYL6, in NIH 3T3 fibroblasts. We found that knockdown of MYL12A/12B in NIH 3T3 cells results in striking changes in cell morphology and dynamics. Remarkably, the levels of MYH9, MYH10 and MYL6 were reduced significantly in knockdown fibroblasts. Comprehensive interaction analysis disclosed that MYL12A, MYL12B and MYL9 can all interact with a variety of MHC IIs in diverse cell and tissue types, but do so optimally with non-muscle types of MHC II. Taken together, our study provides direct evidence that normal levels of non-muscle RLCs are essential for maintaining the integrity of myosin II, and indicates that the RLCs are critical for cell structure and dynamics.
Coherent optical CDMA networks (1993)

Recent work in optical code-division multiple access (CDMA) is reviewed, progressing from incoherent to coherent techniques. It is shown that under appropriate conditions, coherent CDMA can in principle rival wavelength-division multiplexing (WDM) in terms of aggregate network throughput. Furthermore, it is shown that at high data rates, some of the components for WDM are coherent CDMA networks are nearly identical, indicating a similarity between the two approaches. CDMA retains a coding aspect which may prove attractive in security applications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Carotid Artery Plaque Characterization Using CT Multienergy Imaging (2012)

Results of this study suggest that the HU values of plaque may significantly change according to the selected kiloelectron volt; therefore, the HU-based plaque type (fatty, mixed, calcified) should be classified according to the energy level applied.
Use of Partially Phosphorothioated "Antisense" Oligodeoxynucleotides for Sequence-Dependent Modulation of Hematopoiesis in Culture (1994)

To distinguish between sequence-dependent effects and non-specific cytotoxicity of phosphorothioate antisense oligonucleotides (AS-oligos), we introduced AS-oligos blocking expression of 2Hs, the Homo sapiens cell division controller cdc2 kinase, its hematopoietically expressed homolog CHED, and the acetylcholine-hydrolyzing enzyme butyrylcholinesterase (BCHE) into primary murine bone marrow (BM) culture. Antisense oligonucleotides were fully phosphorothioated (Ts) or prepared with three phosphorothioate groups at their 3' termini (S3). Each of these oligos could cause reductions in colony counts either as a result of its sequence-dependent biological capacity or due to sequence-independent cytotoxicity. The Ts and S3 forms of the matching sense oligo, S-BCHE, served for comparison. The S3 forms of AS-2Hs, AS-BCHE, and S-BCHE caused more limited drops in colony counts than their Ts counterparts, reflecting lower cytotoxicity. When incubated with electroblotted BM proteins, Ts but not S3 oligos intensively labeled two protein bands. Moreover, 5'-end 32P-labeled (Ts) S-BCHE labeled nuclear proteins in situ in small, mitotic cells, suggesting correlation between oligo-protein interactions and the sequence-independent cytotoxicity of Ts AS-oligos. Extension of the apparently nontoxic AS-CHED by two adenosine residues at the 3' end, creating a potential for intramolecular hydrogen bond formation, resulted in increased toxicity. These findings recommend the use of nonlooped, partially phosphorothioated oligos for the modulation of hematopoiesis.
Adipose Tissue Expression and Genetic Variants of the Bone Morphogenetic Protein Receptor 1A Gene (BMPR1A) Are Associated With Human Obesity (2009)

Our data suggest that genetic variation in the BMPR1A may play a role in the pathophysiology of human obesity, possibly mediated through effects on mRNA expression.
Transient expression of genes introduced into cultured cells of Drosophila. (1983)

Recombinant plasmids in which the sequence encoding the bacterial chloramphenicol acetyltransferase (CAT; acetyl-CoA:chloramphenicol 3-O-acetyltransferase, EC 2.3.1.28) has been placed under the control of Drosophila heat shock protein 70 (hsp 70) or copia promoters have been introduced into cultured cells of two Drosophila species (Schneider II line of Drosophila melanogaster and D. immigrans) as calcium-phosphate complexes. Within 1-2 days after transfection functional CAT enzyme was detected in cells exposed to either CAT recombinant. The expression of the bacterial information depends on the activity of the Drosophila promoters because plasmids in which the Drosophila DNA fragments were fused to the CAT coding sequence in inverted orientation did not support the synthesis of CAT enzyme activity. Low levels of CAT activity and of hybrid mRNA were detected in cells transformed with hsp-cat recombinants when the cells were maintained at room temperature, and both mRNA levels and CAT activity increased substantially after a brief exposure to 37 degrees C. hsp-cat mRNA has the same 5' terminus as authentic Drosophila hsp 70 messenger. These experiments document a practical system for the introduction and expression of isolated genes in cultured cells of Drosophila.
Baseline CTC subtype to predict outcomes on mCRPC patients (pts) receiving enzalutamide (E) compared to abiraterone (A). (2017)

5070 Background: Prior response to A or E does not predict sensitivity to E following A or A following E. The detection of AR-V7 predicts insensitivity to either drug, but identifies only a portion of non-responders. We previously identified 15 CTC subtypes based on unique phenotypic features in mCRPC pts, each with unique biology and different degree of likelihood of predicting resistance to either drug. Here we explored the relationship between individual subtypes and sensitivity to A vs. E, but not both. Methods: 107 pre-treatment blood samples from mCRPC pts starting A (n = 47) or E (n = 60) as a 1 st or 2 nd line of Tx were analyzed for CTCs utilizing the Epic Sciences platform. Samples were assayed for CTC subtypes based upon 15 pre-defined phenotypic CTC classifiers (Type A-O). Treatment outcomes were assessed by serial PSA changes and landmarked percent time of therapy progression on radiographs, and overall survival following either A or E. Cell type prevalence was also analyzed in relation to clinical outcomes, and subsets of the CTC subtypes subject to single cell NGS to ascertain genomic drivers common to each subtype. Results: CTCs were identified in 94% (101/107) of pt samples. One, cell Type K, found in 25% (27/107) of pts, was associated with a statistically significant inferior outcomes on E for all measures. Whereas similar outcomes were seen between K+ &amp; K- pts treated with A. The distinct features of Cell Type K include a large nucleus, high nuclear entropy and high Nuclear/cytoplasmic AR terminal ratio; and a unique genomic profile enriched for cell cycle and DNA repair alterations relative to other CTC subtypes. Conclusions: The presence of specific CTC subtypes in pre-Rx phlebotomy samples associated with outcomes on A or E. A CTC subtype (Cell Type K) helped to identify pts with poor outcomes on E but not A vs. those without the cell type. Further biologic interrogation of K cells and ongoing clincial validation of the CTC subtype is planned. [Table: see text]
Monoclonal gammopathy of undetermined significance: new insights. (2002)

Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF, et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med 2002; 346:564-9. 

Background: A monoclonal gammopathy of undetermined significance (MGUS) is characterized by the presence of
On the Absorption Spectra of Phenolazopyra zolones in Ionization State (1967)

14種のフェノールアゾピラゾロン誘導体の吸収スペクトルを50vol%エタノール水溶液で,ρHメ_タ_の読みが4.0から0.3N水酸化カリウム溶液の間で測定した。この間のρHでは,フェノール基がさきにイオン化(1段目とする)し,λmaxは長波長側へ移動する。しかしフェノ一ル核中の置換基の陰性度が小さいときは,すぐにピラゾロン核中のC=0基もイオン化(2段目とする)するため, 1価陰イオンの吸収帯が明瞭でなかった。しかし補償法を用いることにより,その吸収位置νmaxを正確に推定することができた。1価陰イオンνmaxとフェノール核中の置換基のHammett定数σ との関係はσ の増大するほど直線的にνmaxが大きくなり, その傾向はイオン化しない状態のベンゼンアゾピラゾロン誘導体での関係と同じになった。このことはヒドラゾン基とピラゾロン基の間に水素結合のあることを示している。2価陰イオンのνmaxとσとの関係はσ の増大するほどνmaxは減少し, ベンゼンアゾピラゾロン誘導体がイオン化したときの関係よりもいちじるしかった。'
A partnership between a selling agent and a buyer's agent could mean better business success - for both agents (2016)

It may seem counterintuitive to form an alliance with a buyer's agent but the advantages to selling agents are compelling and can mean more completed sales.
Effects of potent vitamin D3 analogs on clonal proliferation of human prostate cancer cell lines (1997)

A trial of one or more of these innovative compounds should be considered for treatment of minimal residual disease of prostate cancer.
To Be Targeted: Is the Magic Bullet Concept a Viable Option for Synthetic Nucleic Acid Therapeutics? (2011)

Nucleic acids offer the possibility of tailor-made, individualized treatments for genetic disorders, infectious diseases, and cancer. As an alternative to viral vectors, synthetic delivery systems have a potentially improved safety profile, but often lack sufficient efficiency especially when applied in vivo. Receptor targeting of synthetic vectors can improve the specificity of the vector and increase the efficiency of nucleic acid delivery to the target site. This review covers recent concepts for targeted DNA and RNA delivery to organs like liver and lung, and also to solid cancers. Syntheses and applications of delivery systems targeted with proteins, peptides, and small molecules as ligands coupled to polymeric or lipidic nucleic acid carriers are reviewed. Therapeutic concepts for treatment of genetic and infectious diseases are explained. Systemic treatment regimens of metastasized malignancies in combination with chemotherapy and radiation have already been successfully applied in preclinical studies. In addition, a first clinical study in the human application of a targeted synthetic carrier has been performed.
Primary structure and functional expression of a cDNA encoding the thiazide-sensitive, electroneutral sodium-chloride cotransporter. (1993)

Electroneutral Na+:Cl- cotransport systems are involved in a number of important physiological processes including salt absorption and secretion by epithelia and cell volume regulation. One group of Na+:Cl- cotransporters is specifically inhibited by the benzothiadiazine (thiazide) class of diuretic agents and can be distinguished from Na+:K+:2Cl- cotransporters based on a lack of K+ requirement and insensitivity to sulfamoylbenzoic acid diruetics like bumetanide. We report here the isolation of a cDNA encoding a thiazide-sensitive, electroneutral sodium-chloride cotransporter from the winter flounder urinary bladder using an expression cloning strategy. The pharmacological and kinetic characteristics of the cloned cotransporter are consistent with the properties of native thiazide-sensitive sodium-chloride cotransporters in teleost urinary bladder and mammalian renal distal tubule epithelia. The nucleotide sequence predicts a protein of 1023 amino acids (112 kDa) with 12 putative membrane-spanning regions, which is not related to other previously cloned sodium or chloride transporters. Northern hybridization shows two different gene products: a 3.7-kb mRNA localized only to the urinary bladder and a 3.0-kb mRNA present in several non-bladder/kidney tissues.
Targeted inactivation of αi2or αi3disrupts activation of the cardiac muscarinic K+channel, IK+Ach, in intact cells (1997)

Cardiac muscarinic receptors activate an inwardly rectifying K+ channel, IK+Ach, via pertussis toxin (PT)-sensitive heterotrimeric G proteins (in heart Gi2, Gi3, or Go). We have used embryonic stem cell (ES cell)-derived cardiocytes with targeted inactivations of specific PT-sensitive alpha subunits to determine which G proteins are required for receptor-mediated regulation of IK+Ach in intact cells. The muscarinic agonist carbachol increased IK+Ach activity in ES cell-derived cardiocytes from wild-type cells, in cells lacking alphao, and in cells lacking the PT-insensitive G protein alphaq. In cells with targeted inactivation of alphai2 or alphai3, channel activation by both carbachol and adenosine was blocked. Carbachol-induced channel activation was restored in the alphai2- and alphai3-null cells by reexpressing the previously targeted gene and guanosine 5'-[gamma-thio] triphosphate was able to fully activate IK+Ach in excised membranes patches from these mutants. In contrast, negative chronotropic responses to both carbachol and adenosine were preserved in cells lacking alphai2 or alphai3. Our results show that expression of two specific PT-sensitive alpha subunits (alphai2 and alphai3 but not alphao) is required for normal agonist-dependent activation of IK+Ach and suggest that both alphai2- and alphai3-containing heterotrimeric G proteins may be involved in the signaling process. Also the generation of negative chronotropic responses to muscarinic or adenosine receptor agonists do not require activation of IK+Ach or the expression of alphai2 or alphai3.
Purification and characterization of a DNA helicase from Saccharomyces cerevisiae (2021)

A novel DNA helicase, scHelI, has been purified from whole cell extracts of Saccharomyces cerevisiae using biochemical assays to monitor the fractionation. The enzyme unwinds partial duplex DNA substrates, as long as 343 base pairs in length, in a reaction that is dependent on either ATP or dATP hydrolysis. scHelI also catalyzes a single-stranded DNA-dependent ATP hydrolysis reaction; the apparent Km for ATP is 325 microM. The unwinding reaction on circular partial duplex substrates is biphasic, with a fast component occurring within 5 min of the initiation of the reaction and a slow component continuing to 60 min. This is in contrast to the ATP hydrolysis reaction, which exhibits linear kinetics for 60 min. The direction of the unwinding reaction is 5' to 3' with respect to the strand of DNA on which the enzyme is bound. The unwinding reaction is strongly stimulated by the addition of Escherichia coli single-stranded DNA-binding protein when long partial duplex substrates are used. The enzymatic activity of scHelI copurifies with a polypeptide of 135 kDa as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The polypeptide sediments as a monomer in a glycerol gradient in the presence of 0.2 M NaCl.
The reactivity of bromine atoms in brominated pyridines. The preparation of 3‐acetylamino‐5‐ethoxypyridine from 3,5‐dibromopyridine (1948)

Abstract 3‐Acetylamino‐5‐ethoxypyridine was prepared by converting 3,5‐dibromopyridine with sodium ethylate into 3‐bromo‐5‐ethoxypyridine, allowing this substance to interact with ammonia and acetylating the aminoethoxypyridine thus formed with acetic anhydride.
Molecular Self-Healing Processes in Polymers (2005)

A critical review of self-healing processes in polymers and composites based on polymeric matrices is presented. Two self-healing processes are analyzed, one “operating” within micron range and the other at molecular scale. Preliminary data on the molecular self-healing process in living polymers, as obtained by electron spin resonance are discussed. The possibility to develop a multi-scale self-healing material is suggested.
Endometriosis Is Associated with Rare Copy Number Variants (2014)

Endometriosis is a complex gynecological condition that affects 6-10% of women in their reproductive years and is defined by the presence of endometrial glands and stroma outside the uterus. Twin, family, and genome-wide association (GWA) studies have confirmed a genetic role, yet only a small part of the genetic risk can be explained by SNP variation. Copy number variants (CNVs) account for a greater portion of human genetic variation than SNPs and include more recent mutations of large effect. CNVs, likely to be prominent in conditions with decreased reproductive fitness, have not previously been examined as a genetic contributor to endometriosis. Here we employ a high-density genotyping microarray in a genome-wide survey of CNVs in a case-control population that includes 2,126 surgically confirmed endometriosis cases and 17,974 population controls of European ancestry. We apply stringent quality filters to reduce the false positive rate common to many CNV-detection algorithms from 77.7% to 7.3% without noticeable reduction in the true positive rate. We detected no differences in the CNV landscape between cases and controls on the global level which showed an average of 1.92 CNVs per individual with an average size of 142.3 kb. On the local level we identify 22 CNV-regions at the nominal significance threshold (P<0.05), which is greater than the 8.15 CNV-regions expected based on permutation analysis (P<0.001). Three CNV's passed a genome-wide P-value threshold of 9.3 × 10(-4); a deletion at SGCZ on 8p22 (P = 7.3 × 10(-4), OR = 8.5, Cl = 2.3-31.7), a deletion in MALRD1 on 10p12.31 (P = 5.6 × 10(-4), OR = 14.1, Cl = 2.7-90.9), and a deletion at 11q14.1 (P = 5.7 × 10(-4), OR = 33.8, Cl = 3.3-1651). Two SNPs within the 22 CNVRs show significant genotypic association with endometriosis after adjusting for multiple testing; rs758316 in DPP6 on 7q36.2 (P = 0.0045) and rs4837864 in ASTN2 on 9q33.1 (P = 0.0002). Together, the CNV-loci are detected in 6.9% of affected women compared to 2.1% in the general population.
Preparation of Polystyrene- and Silica-Coated Gold Nanorods and Their Use as Templates for the Synthesis of Hollow Nanotubes (2001)

We report the preparation of polystyrene and silica-coated Au nanorods (aspect ratio 13 with 16 nm short axis). The coating resulted in a modification of the optical properties of the Au nanorods. Dissolution of the Au core from the polystyrene- and silica-coated Au nanorods using KCN enabled the formation of hollow polystyrene and silica nanotubes.
Genome‐wide search for schizophrenia susceptibility loci: The NIMH genetics initiative and millennium consortium (1998)

Schizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors. The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessment and systematic ascertainment procedures. The NIMH Genetics Initiative on Schizophrenia, a multisite collaborative study, was established as a national resource with a centralized clinical data base and cell repository. The Millennium Schizophrenia Consortium has completed a genome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schizophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 marker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European descent in their average heterozygosity (79% vs. 76%, P < .0001) and number of alleles per marker (9.2 vs. 8.4, P < .0001). Also, the allele frequencies of 73% of the marker loci differed significantly (P < .01) between individuals of European and African ancestry. However, regardless of ethnic background, this sample was largely comprised of schizophrenics with more than a decade of psychosis associated with pervasive social and occupational impairment. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:275–281, 1998. © 1998 Wiley-Liss, Inc.
Efficient Synthesis of Monoacyl Dipyrromethanes and Their Use in the Preparation of Sterically Unhindered trans-Porphyrins (2000)

The condensation of an aldehyde with a dipyrromethane bearing a sterically unhindered aryl substituent at the 5-position typically results in low yield and a mixture of porphyrin products derived from acidolytic scrambling. We have developed a concise nonscrambling synthesis of such trans-porphyrins that takes advantage of the availability of multigram quantities of dipyrromethanes. This route involves the selective monoacylation of the dipyrromethanes with a pyridyl thioester, reduction of the monoacyl dipyrromethane to the corresponding carbinol, and self-condensation of the carbinol to form the porphyrin. The monoacylation procedure has wide scope as demonstrated by the preparation of a set of 15 diverse monoacyl dipyrromethanes in good yield at the multigram scale. The dipyrromethanecarbinol self-condensation reaction is extremely rapid (<3 min) under mild room-temperature conditions and affords the trans-porphyrin in 16-28% yield. Analysis by laser-desorption mass spectrometry (LD-MS) of samples from the crude reaction mixture revealed no scrambling within the limit of detection (1 part in 100). The self-condensation is compatible with a range of electron-withdrawing or -releasing substituents as well as substituents for building block applications (TMS-ethyne, ethyne, iodo, ester). The absence of any detectable scrambling in the self-condensation enables a simple purification. The synthesis readily affords gram quantities of pure, sterically unhindered trans-porphyrins in a process involving minimal chromatography.
Targeted Integration of T-DNA into the Tobacco Genome at Double-Stranded Breaks: New Insights on the Mechanism of T-DNA Integration (2003)

Agrobacterium tumefaciens T-DNA normally integrates into random sites in the plant genome. We have investigated targeting of T-DNA by nonhomologous end joining process to a specific double-stranded break created in the plant genome by I-CeuI endonuclease. Sequencing of genomic DNA/T-DNA junctions in targeted events revealed that genomic DNA at the cleavage sites was usually intact or nearly so, whereas donor T-DNA ends were often resected, sometimes extensively, as is found in random T-DNA inserts. Short filler DNAs were also present in several junctions. When an I-CeuI site was placed in the donor T-DNA, it was often cleaved by I-CeuI endonuclease, leading to precisely truncated targeted T-DNA inserts. Their structure requires that T-DNA cutting occurred before or during integration, indicating that T-DNA is at least partially double stranded before integration is complete. This method of targeting full-length T-DNA with considerable fidelity to a chosen break point in the plant genome may have experimental and practical applications. Our findings suggest that insertion at break points by nonhomologous end joining is one normal mode of entry for T-DNA into the plant genome.
[18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease (2013)

[(18)F]T807 demonstrates high affinity and selectivity to PHF-tau as well as favorable in vivo properties, making this a promising candidate as an imaging agent for AD.
Activation of H2O2 by Chiral Confined Brønsted Acids: A Highly Enantioselective Catalytic Sulfoxidation (2012)

Confined chiral Brønsted acids are shown to catalyze asymmetric oxidations of sulfides to sulfoxides with hydrogen peroxide. The wide generality and high enantioselectivity of the developed method compare even to the best metal-based systems and suggest utility in other asymmetric oxidations.
A closer look at GPUs (2008)

As the line between GPUs and CPUs begins to blur, it's important to understand what makes GPUs tick.