gebhart/patrepeval huggingface dataset:
Construction and characterization of amplifiable multicopy DNA cloning vehicles derived from the P15A cryptic miniplasmid (1978)

Construction and characterization of a class of multicopy plasmid cloning vehicles containing the replication system of miniplasmid P15A are described. The constructed plasmids have cleavage sites within antibiotic resistance genes for a variety of commonly employed site-specific endonucleases, permitting convenient use of the insertional inactivation procedure for the selection of clones that contain hybrid DNA molecules. Although the constructed plasmids showed DNA sequence homology with the ColE1 plasmid within the replication region, were amplifiable by chloramphenicol or spectinomycin, required DNA polymerase I for replication, and shared other replication properties with ColE1, they were nevertheless compatible with ColE1. P15A-derived plasmids were not self-transmissible and were mobilized poorly by Hfr strains; however, mobilization was complemented by the presence of a ColE1 plasmid within the same cell.
Protection of Endothelial Survival by Peroxisome Proliferator-Activated Receptor-δ Mediated 14-3-3 Upregulation (2006)

PGI2 protects ECs from H2O2-induced apoptosis by inducing PPARdelta binding to 14-3-3alpha promoter, thereby upregulating 14-3-3alpha protein expression. Elevated 14-3-3alpha augments Bad sequestration and prevents Bad-triggered apoptosis.
FimZ Is a Molecular Link between Sticking and Swimming in Salmonella enterica Serovar Typhimurium (2002)

Salmonella enterica serovar Typhimurium produces two types of filamentous appendages on its surface. Fimbriae mediate adherence to tissues and cells via receptor-specific interactions, and flagella are the organelles of motility. These appendages play a role in colonization and dissemination, respectively, from infected surfaces and may be important components of bacterial survival. Increased expression of FimZ in serovar Typhimurium resulted in bacteria which were hyperfimbriated but were nonmotile in soft agar. This lack of motility was associated with down regulation of the flhDC master flagellar operon. Therefore, FimZ represents a molecular connection between flagella and fimbrial formation in serovar Typhimurium, indicating that the synthesis of flagella and fimbriae are oppositely controlled.
The Utility of Basal Cell—Specific Anti-Cytokeratin Antibody (34βE12) in the Diagnosis of Prostate Cancer (1995)

Basal cell-specific anti-cytokeratin antibody (34 beta E12) decorates the basal cells of benign prostatic epithelium by standard immunohistochemical techniques, whereas adenocarcinoma of the prostate lacks immunoreactivity with this antibody. We reviewed our experience with this antibody to determine its utility in the diagnosis of adenocarcinoma of the prostate as well as its pattern of usage at a tertiary medical center. In all, 7,242 prostate specimens from 5,262 men were seen at Johns Hopkins Hospital between 1/89 and 4/93. Immunostaining for basal cell-specific cytokeratin (34 beta E12) was originally used for diagnostic purposes in 289 questionable area from 228 cases; 45% of these cases were seen in consultation. The distribution of cases using 34 beta E12 was 52% needle biopsies, 32% transurethral prostatic resections (TURPs). 13% radical prostatectomies, and 3% open enucleations. These procedures constituted 2.8% of all needle biopsies, 7.2% of all TURPs, 1.7% of all radical prostatectomies, and 3.5% of all enucleations seen during this time period. For this study the hematoxylin and eosin stain was reviewed without knowledge of the original diagnosis, a diagnosis was favored, the 34 beta E12 stain was examined, and a final diagnosis was determined. The 34 beta E12 stain established (14%), confirmed (58%), or changed (2%) our favored diagnoses, while 18% remained or became equivocal. The 34 beta E12 stain was of no use in 8% of the cases, yet we felt we were still able to render a final diagnosis even without the help of the stain. The differential diagnoses in the questionable foci using 34 beta E12 were cancer versus focus of atypical glands (44%), adenosis (39%), prostatic intraepithelial neoplasia (PIN) (8%), basal cell hyperplasia (5%), and atrophy (4%). However, 34 beta E12 was used in only 15-20% of all cases of adenosis and basal cell hyperplasia and in < 2% of PIN and atrophy cases seen during this time. Reasons for equivocal results were loss of suspicious glands on cut downs used for staining (49%), too few glands to rely on negative staining (23%), technical problems (15%), limited number of positive staining glands in a small focus (7%), and cautery artifact (6%). Although equivocal cases tended to have fewer negative stained glands than cases diagnosed with cancer, there was no minimum number of negative stained glands required to establish a diagnosis of cancer. From these data we conclude that 34 beta E12 staining is a useful tool in confirming, establishing, or changing the diagnosis in questionable foci seen in the everyday practice of surgical pathology.(ABSTRACT TRUNCATED AT 400 WORDS)
HSF access to heat shock elements in vivo depends critically on promoter architecture defined by GAGA factor, TFIID, and RNA polymerase II binding sites. (1995)

Chromatin structure can modulate gene expression by limiting transcription factor access to gene promoters. We examined sequence elements of the Drosophila hsp70 promoter for their ability to facilitate the binding of the transcription factor, heat shock factor (HSF), to chromatin. We assayed HSF binding to various transgenic heat shock promoters in situ by measuring amounts of fluorescence at transgenic loci of polytene chromosomes that were stained with an HSF antibody. We found three promoter sequences that influence the access of HSF to its binding sites: the GAGA element, sequences surrounding the transcription start site, and a region in the leader of hsp70 where RNA polymerase II arrests during early elongation. The GAGA element has been shown previously to disrupt nucleosome structure. Because the two other critical regions include sequences that are required for stable binding of TFIID in vitro, we examined the in vivo occupancy of the TATA elements in the transgenic promoters. We found that TATA occupancy correlated with HSF binding for some promoters. However, in all cases HSF accessibility correlated with the presence of paused RNA polymerase II. We propose that a complex promoter architecture is established by multiple interdependent factors, including GAGA factor, TFIID, and RNA polymerase II, and that this structure is critical for HSF binding in vivo.
Effective Approaches to Attention-based Neural Machine Translation (2015)

An attentional mechanism has lately been used to improve neural machine translation (NMT) by selectively focusing on parts of the source sentence during translation. However, there has been little work exploring useful architectures for attention-based NMT. This paper examines two simple and effective classes of attentional mechanism: a global approach which always attends to all source words and a local one that only looks at a subset of source words at a time. We demonstrate the effectiveness of both approaches on the WMT translation tasks between English and German in both directions. With local attention, we achieve a significant gain of 5.0 BLEU points over non-attentional systems that already incorporate known techniques such as dropout. Our ensemble model using different attention architectures yields a new state-of-the-art result in the WMT'15 English to German translation task with 25.9 BLEU points, an improvement of 1.0 BLEU points over the existing best system backed by NMT and an n-gram reranker. 1
A review of the role of radiation therapy in the treatment of patients with breast cancer. (1991)

Irradiation has been used to treat cancer of the breast since 1895. Over the period between 1895 to the present, the therapeutic use of irradiation has evolved from a cauterizing agent to a sophisticated use of theory and practice to cause tumor cell death while at the same time producing maximum normal tissue sparing. The use of radiation has made it possible for the surgeon to use conservative breast sparing surgery to obtain excellent cosmetic results, while at the same time producing a local control equal to that of mastectomy. For the patient, conservative surgery becomes a better option than mastectomy because it not only produces local control equal to that of mastectomy, but gives the wonderful added benefit of a more superior and pleasing cosmetic result.
Switchable Hydrogels Obtained by Supramolecular Cross‐Linking of Adamantyl‐Containing LCST Copolymers with Cyclodextrin Dimers (2006)

En route to intelligent hydrogels: Copolymers of N-isopropylacrylamide containing adamantyl groups can be cross-linked noncovalently with cyclodextrin dimers. This results in thermosensitive hydrogels with cloud points that are lower than those of the pure copolymers. Addition of monomeric methylated cyclodextrin results in an increase in the cloud points but has no significant influence on the viscosity of the copolymer solution.
Controlling mRNA stability and translation with the CRISPR endoribonuclease Csy4 (2015)

The bacterial CRISPR endoribonuclease Csy4 has recently been described as a potential RNA processing tool. Csy4 recognizes substrate RNA through a specific 28-nt hairpin sequence and cleaves at the 3' end of the stem. To further explore applicability in mammalian cells, we introduced this hairpin at various locations in mRNAs derived from reporter transgenes and systematically evaluated the effects of Csy4-mediated processing on transgene expression. Placing the hairpin in the 5' UTR or immediately after the start codon resulted in efficient degradation of target mRNA by Csy4 and knockdown of transgene expression by 20- to 40-fold. When the hairpin was incorporated in the 3' UTR prior to the poly(A) signal, the mRNA was cleaved, but only a modest decrease in transgene expression (∼2.5-fold) was observed. In the absence of a poly(A) tail, Csy4 rescued the target mRNA substrate from degradation, resulting in protein expression, which suggests that the cleaved mRNA was successfully translated. In contrast, neither catalytically inactive (H29A) nor binding-deficient (R115A/R119A) Csy4 mutants were able to exert any of the effects described above. Generation of a similar 3' end by RNase P-mediated cleavage was unable to rescue transgene expression independent of Csy4. These results support the idea that the selective generation of the Csy4/hairpin complex resulting from cleavage of target mRNA might serve as a functional poly(A)/poly(A) binding protein (PABP) surrogate, stabilizing the mRNA and supporting translation. Although the exact mechanism(s) remain to be determined, our studies expand the potential utility of CRISPR nucleases as tools for controlling mRNA stability and translation.
Metabolism of Triiodothyronine in Rat Hepatocytes* (1989)

The metabolism of T3 by isolated rat hepatocytes was analyzed by Sephadex LH-20 chromatography, HPLC, and RIA for T3 sulfate (T3S) and 3,3'-diiodothyronine (3,3'-T2). Type I iodothyronine deiodinase activity was inhibited with propylthiouracil (PTU), and phenol sulfotransferase activity by SO4(2-) depletion or with competitive substrates or inhibitors. Under normal conditions, labeled T3 glucuronide and I- were the main products of [3'-125I]T3 metabolism. Iodide production was decreased by inhibition (PTU) or saturation (greater than 100 nM T3) of type I deiodinase, which was accompanied by the accumulation of T3S and 3,3'-T2S. Inhibition of phenol sulfotransferase resulted in decreased iodide production, which was associated with an accumulation of 3,3'-T2 and 3,3'-T2 glucuronide, independent of PTU. Formation of 3,3'-T2 and its conjugates was only observed at T3 substrate concentrations below 10 nM. Thus, T3 is metabolized in rat liver cells by three quantitatively important pathways: glucuronidation, sulfation, and direct inner ring deiodination. Whereas T3 glucuronide is not further metabolized in the cultures, T3S is rapidly deiodinated by the type I enzyme. As confirmed by incubations with isolated rat liver microsomes, direct inner ring deiodination of T3 is largely mediated by a low Km, PTU-insensitive, type III-like iodothyronine deiodinase, and production of 3,3'-T2 is only observed if its rapid sulfation is prevented.
p38 Mitogen-Activated Protein Kinase Mediates the Fas-Induced Mitochondrial Death Pathway in CD8+ T Cells (2006)

The p38 mitogen-activated protein kinase (MAPK) signaling pathway can be activated by a variety of stress stimuli such as UV radiation and osmotic stress. The regulation and role of this pathway in death receptor-induced apoptosis remain unclear and may depend on the specific death receptor and cell type. Here we show that binding of Fas ligand to Fas activates p38 MAPK in CD8+ T cells and that activation of this pathway is required for Fas-mediated CD8+ T-cell death. Active p38 MAPK phosphorylates Bcl-xL and Bcl-2 and prevents the accumulation of these antiapoptotic molecules within the mitochondria. Consequently, a loss of mitochondrial membrane potential and the release of cytochrome c lead to the activation of caspase 9 and, subsequently, caspase 3. Therefore, the activation of p38 MAPK is a critical link between Fas and the mitochondrial death pathway and is required for the Fas-induced apoptosis of CD8+ T cells.
The Promise of Poop (2013)

Fecal transplants offer hope for treating many diseases. But they need to be studied more scientifically, says one of the treatment's pioneers.
Precise Ablation of Skin With Reduced Collateral Damage Using the Femtosecond-Pulsed, Terawatt Titanium-Sapphire Laser (1993)

The results suggest that ablation of skin with femtosecond-pulsed, terawatt Ti:Al2O3 laser may have potential for precision cutaneous surgery, and in vivo studies are indicated.
Treatment of severe psoriasis with fumaric acid esters: scientific background and guidelines for therapeutic use (1999)

Fumaric acid ester (FAE) therapy has proved to be safe and effective in patients with severe psoriasis vulgaris. This treatment was introduced nearly 30 years ago, but is only now gaining renewed interest among dermatologists. FAE therapy is licensed in Germany and registration is pending in many European countries. Multicentre trials have confirmed the beneficial effect of FAE in psoriasis and have defined the spectrum of its adverse effects. Although the mode of action of FAEs in the treatment of psoriasis is not fully understood, recent experimental data point towards a skewing of the Th1-dominated T-cell response in psoriasis to a Th2-like pattern, and inhibition of proliferation of keratinocytes. This article reviews the experimental and clinical information on FAEs in psoriasis and provides guidelines for the clinical use of FAEs derived from a consensus meeting of leading experts.
The GCN2 eIF2α Kinase Is Required for Adaptation to Amino Acid Deprivation in Mice (2002)

The GCN2 eIF2alpha kinase is essential for activation of the general amino acid control pathway in yeast when one or more amino acids become limiting for growth. GCN2's function in mammals is unknown, but must differ, since mammals, unlike yeast, can synthesize only half of the standard 20 amino acids. To investigate the function of mammalian GCN2, we have generated a Gcn2(-/-) knockout strain of mice. Gcn2(-/-) mice are viable, fertile, and exhibit no phenotypic abnormalities under standard growth conditions. However, prenatal and neonatal mortalities are significantly increased in Gcn2(-/-) mice whose mothers were reared on leucine-, tryptophan-, or glycine-deficient diets during gestation. Leucine deprivation produced the most pronounced effect, with a 63% reduction in the expected number of viable neonatal mice. Cultured embryonic stem cells derived from Gcn2(-/-) mice failed to show the normal induction of eIF2alpha phosphorylation in cells deprived of leucine. To assess the biochemical effects of the loss of GCN2 in the whole animal, liver perfusion experiments were conducted. Histidine limitation in the presence of histidinol induced a twofold increase in the phosphorylation of eIF2alpha and a concomitant reduction in eIF2B activity in perfused livers from wild-type mice, but no changes in livers from Gcn2(-/-) mice.
A Novel Nonsense Mutation inCEP290Induces Exon Skipping and Leads to a Relatively Mild Retinal Phenotype (2010)

PURPOSE. To identify the genetic defect in a family with variable retinal phenotypes. The proband had a diagnosis of Leber congenital amaurosis (LCA), whereas her two cousins had an early-onset severe retinal dystrophy (EOSRD) with useful vision. A distant family member had retinitis pigmentosa (RP). METHODS. DNA samples of the affected family members were genotyped with 250 K genome-wide SNP microarrays. Genetic defects were localized by linkage analysis and homozygosity mapping, and candidate genes were analyzed by sequencing. Patients underwent a full ophthalmic examination. RESULTS. Compound heterozygous mutations in CEP290 were identified in the proband and her two cousins: the frequent c.2991+1655A>G founder mutation and a novel nonsense mutation in exon 7 (c.451C>T, p.Arg151X). The proband had nystagmus, hyperopia, a flat electroretinogram (ERG), and decreased visual acuity (20/250) from birth. The two cousins had minimal scotopic ERG responses at the age of 2. In one of these patients, visual acuity had reached a level of 20/32 at age 5, which is high for patients with CEP290 mutations. Analysis of the CEP290 mRNA in affected individuals revealed altered splice forms in which either exon 7 or exons 7 and 8 were skipped. In both mutant cDNA products, the open reading frame was not disrupted. Furthermore, homozygosity mapping and mutation analysis in the distant family member affected by RP revealed a homozygous mutation in MERTK, but no CEP290 mutations. This MERTK mutation was heterozygously present in the most severely affected (LCA) patient, but was absent in the two more mildly affected cousins. CONCLUSIONS. A novel nonsense mutation in CEP290 results in nonsense-associated altered splicing. That the remaining open reading frame is intact may explain the less severe phenotype observed in the two affected cousins. The additional heterozygous mutation in MERTK may clarify the more severe phenotype in the proband. This study extends the phenotypic spectrum of CEP290-associated diseases at the mild end.
Taste Evaluations of Angiotensin I Converting Enzyme Inhibitors, Leu-Lys-Tyr Analogues (1995)

Tastes of Leu-Lys-Tyr (LKY) analogues, a series of potent angiotensin I converting enzyme (ACE) inhibitory peptides were evaluated. Some of these analogues were found to be sweet, such as Val-Lys-Tyr and Ala-Orn-Tyr. Furthermore, the structural requirements for sweetness or decreasing the bitterness were investigated by considerations of the structure-taste relationship with LKY analogues.
Resolutions with metal complexes. Preparation and resolution of (R,S)-methylphenyl(8-quinolyl)phosphine and its arsenic analog. Crystal and molecular structure of (+)589-[(R)-dimethyl(1-ethyl-.alpha.-naphthyl)aminato-C2,N][(S)-methylphenyl(8-quinolyl)phosphine]palladium(II) hexafluorophosphate (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTResolutions with metal complexes. Preparation and resolution of (R,S)-methylphenyl(8-quinolyl)phosphine and its arsenic analog. Crystal and molecular structure of (+)589-[(R)-dimethyl(1-ethyl-.alpha.-naphthyl)aminato-C2,N][(S)-methylphenyl(8-quinolyl)phosphine]palladium(II) hexafluorophosphateDavid G. Allen, George M. McLaughlin, Glen B. Robertson, William L. Steffen, Geoffrey Salem, and Stanley Bruce WildCite this: Inorg. Chem. 1982, 21, 3, 1007–1014Publication Date (Print):March 1, 1982Publication History Published online1 May 2002Published inissue 1 March 1982https://pubs.acs.org/doi/10.1021/ic00133a027https://doi.org/10.1021/ic00133a027research-articleACS PublicationsRequest reuse permissionsArticle Views474Altmetric-Citations142LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Intravenous Administration of Human Bone Marrow Stromal Cells Induces Angiogenesis in the Ischemic Boundary Zone After Stroke in Rats (2003)

We tested the hypothesis that intravenous infusion of human bone marrow stromal cells (hMSCs) promotes vascular endothelial growth factor (VEGF) secretion, VEGF receptor 2 (VEGFR2) expression and angiogenesis in the ischemic boundary zone (IBZ) after stroke. hMSCs (1x10(6)) were intravenously injected into rats 24 hours after middle cerebral artery occlusion (MCAo). Laser scanning confocal microscopy (LSCM), immunohistochemistry and ELISA were performed to assay angiogenesis and levels of human and rat VEGF in the host brain, respectively. In addition, capillary-like tube formation was measured using mouse brain-derived endothelial cells (MBDECs). Morphological and three dimensional image analyses revealed significant (P<0.05) increases in numbers of enlarged and thin walled blood vessels and numbers of newly formed capillaries at the boundary of the ischemic lesion in rats (n=12) treated with hMSCs compared with numbers in rats (n=12) treated with PBS. ELISA measurements showed that treatment with hMSCs significantly (P<0.05) raised endogenous rat VEGF levels in the IBZ from 10.5+/-1.7 ng/mL in the control group to 17.5+/-1.6 ng/mL in the hMSC-treated group. In addition, treatment with hMSCs increased endogenous VEGFR2 immunoreactivity. In vitro, when MBDECs were incubated with the supernatant obtained from cultured hMSCs, capillary-like tube formation was significantly (P<0.01) induced. However, hMSC-induced capillary-like tube formation was significantly (P<0.01) inhibited when the endothelial cells were incubated with the supernatant from hMSCs in the presence of a neutralizing anti-VEGFR2. These data suggest that treatment of stroke with hMSCs enhances angiogenesis in the host brain and hMSC-enhanced angiogenesis is mediated by increases in levels of endogenous rat VEGF and VEGFR2.