gebhart/patrepeval huggingface dataset:
A rapid method for efficient gene replacement in the filamentous fungus Aspergillus nidulans (2000)

The construction of mutant fungal strains is often limited by the poor efficiency of homologous recombination in these organisms. Higher recombination efficiencies can be obtained by increasing the length of homologous DNA flanking the transformation marker, although this is a tedious process when standard molecular biology techniques are used for the construction of gene replacement cassettes. Here, we present a two-step technology which takes advantage of an Escherichia coli strain expressing the phage lambda Red(gam, bet, exo) functions and involves (i) the construction in this strain of a recombinant cosmid by in vivo recombination between a cosmid carrying a genomic region of interest and a PCR-generated transformation marker flanked by 50 bp regions of homology with the target DNA and (ii) genetic exchange in the fungus itself between the chromosomal locus and the circular or linearized recombinant cosmid. This strategy enables the rapid establishment of mutant strains carrying gene knock-outs with efficiencies >50%. It should also be appropriate for the construction of fungal strains with gene fusions or promoter replacements.
CART Classification of Human 5' UTR Sequences (2000)

A nonredundant database of 2312 full-length human 5'-untranslated regions (UTRs) was carefully prepared using state-of-the-art experimental and computational technologies. A comprehensive computational analysis of this data was conducted for characterizing the 5' UTR features. Classification and regression tree (CART) analysis was used to classify the data into three distinct classes. Class I consists of mRNAs that are believed to be poorly translated with long 5' UTRs filled with potential inhibitory features. Class II consists of terminal oligopyrimidine tract (TOP) mRNAs that are regulated in a growth-dependent manner, and class III consists of mRNAs with favorable 5' UTR features that may help efficient translation. The most accurate tree we found has 92.5% classification accuracy as estimated by cross validation. The classification model included the presence of TOP, a secondary structure, 5' UTR length, and the presence of upstream AUGs (uAUGs) as the most relevant variables. The present classification and characterization of the 5' UTRs provide precious information for better understanding the translational regulation of human mRNAs. Furthermore, this database and classification can help people build better computational models for predicting the 5'-terminal exon and separating the 5' UTR from the coding region.
G-protein beta gamma dimers. Membrane targeting requires subunit coexpression and intact gamma C-A-A-X domain. (1991)

Attachment of heterotrimeric G-proteins to the inner face of the plasma membrane is fundamental to their role as signal transducers by allowing interaction with both receptors and effectors. Certain G-protein alpha subunits are anchored to the membrane by covalent myristoylation. The beta gamma complex is required for G-protein interaction with receptors and is independently membrane associated through an unknown mechanism. A series of carboxyl-terminal modifications including isoprenylation which may contribute to membrane attachment has been identified recently in G-protein gamma subunits. Expression and membrane targeting of beta and gamma subunits were examined in COS cells. The expression of either subunit was found to require cotransfection with both beta and gamma cDNAs. Mutation of the carboxyl-terminal cysteine residue of gamma shown to undergo isoprenylation and carboxymethyl-esterification preserved beta gamma expression but blocked isoprenylation and membrane attachment. These results implicate the carboxyl-terminal processing of G-protein gamma subunits and beta coexpression as necessary and sufficient for membrane targeting of the beta gamma complex.
Free α subunit of human chorionic gonadotrophin: molecular basis of immunologically and biologically active domains (1994)

Immunochemical studies were undertaken to identify surface-orientated epitopes of the free alpha subunit of human chorionic gonadotrophin (hCG-alpha) at the amino acid sequence level. We investigated the molecular organization of these epitopes, resolved the immunological topography in terms of spatial arrangement of antigenic domains and related structures to functions such as subunit association or receptor binding. Overlapping synthetic peptides covering the entire amino acid sequence of hCG-alpha, an enzymatically digested hCG-alpha subunit, and a reduced and alkylated hCG-alpha preparation were assayed in a solid-phase one-site enzyme-linked immunoassay, and in a solution-phase competitive radioimmunoassay (RIA). The antigenic topography was mapped by monoclonal antibodies (MCAs) in two-site binding assays (sandwich RIA). On the surface of hCG-alpha, seven different epitopes (alpha 1-alpha 7), arranged in four spatially distinct domains, could be distinguished: A, alpha 1,2,4; B, alpha 3,5; C, alpha 6; D, alpha 7. The peptides spanning hCG-alpha(13-18), hCG-alpha(17-22) and hCG-alpha(33-42) appeared to contribute to the formation of epitopes alpha 2, alpha 4 and alpha 6 respectively. Since epitope alpha 6 is present only on the free non-assembled subunit of different species, we concluded that the region hCG-alpha(33-42), which is evolutionarily highly conserved, represents a subunit assembly site. All but one epitope (alpha 7) are destroyed by reducing and alkylating hCG-alpha. In contrast, chymotryptic digestion of hCG-alpha, leading to release of the heptapeptide hCG-alpha(41-47), did not affect epitope expression, indicating that this sequence is not involved in the formation of antigenic determinants. Addressing the biological properties of hCG-alpha epitopes by radioreceptor assay revealed that the three hCG-alpha peptides corresponding to epitopes alpha 2, alpha 4 and alpha 6 did not displace radiolabelled hCG from its receptor, whereas any of the MCAs directed against determinants (alpha 1-alpha 5), shared by hCG and hCG-alpha, totally inhibited binding. Consistent with this, the antibodies neutralized the biological activity of hCG in terms of testosterone production in a mouse Leydig cell in vitro bioassay. We therefore concluded that hormone antibody-binding sites differ from those of hormone receptor binding, revealing no essential congruence of immunologically and biologically active domains.
The pathophysiology of lymphedema (1998)

The primary insult to the axillary lymphatic system by surgery and radiotherapy presumably is the root cause of PME; however, there is strong evidence to suggest that hemodynamic factors are contributory to the chronic swelling.
Neural Wiskott-Aldrich syndrome protein modulates Wnt signaling and is required for hair follicle cycling in mice (2010)

The Rho family GTPases Cdc42 and Rac1 are critical regulators of the actin cytoskeleton and are essential for skin and hair function. Wiskott-Aldrich syndrome family proteins act downstream of these GTPases, controlling actin assembly and cytoskeletal reorganization, but their role in epithelial cells has not been characterized in vivo. Here, we used a conditional knockout approach to assess the role of neural Wiskott-Aldrich syndrome protein (N-WASP), the ubiquitously expressed Wiskott-Aldrich syndrome-like (WASL) protein, in mouse skin. We found that N-WASP deficiency in mouse skin led to severe alopecia, epidermal hyperproliferation, and ulceration, without obvious effects on epidermal differentiation and wound healing. Further analysis revealed that the observed alopecia was likely the result of a progressive and ultimately nearly complete block in hair follicle (HF) cycling by 5 months of age. N-WASP deficiency also led to abnormal proliferation of skin progenitor cells, resulting in their depletion over time. Furthermore, N-WASP deficiency in vitro and in vivo correlated with decreased GSK-3beta phosphorylation, decreased nuclear localization of beta-catenin in follicular keratinocytes, and decreased Wnt-dependent transcription. Our results indicate a critical role for N-WASP in skin function and HF cycling and identify a link between N-WASP and Wnt signaling. We therefore propose that N-WASP acts as a positive regulator of beta-catenin-dependent transcription, modulating differentiation of HF progenitor cells.
Epithelial Peroxidase and Endometrial Granulocytes in the Normal Cyclic Human Endometrium* (1983)

Studies in animal models have clearly shown a relationship between the administration of estrogens and the appearance of peroxidase activity in growth-responsive estrogen target tissues (endometrium, cervix, vagina, breast, and DMBA rat mammary tumor). We have studied the ultrastructural localization of endogenous peroxidase activity in the normal cyclic human endometrium. Endogenous peroxidase activity was not identified in proliferative phase endometria, with the exception of one very late proliferative phase endometrium. Most secretory phase endometria showed at least some ultrastructurally identified peroxidase activity in glandular epithelial cells. The number of epithelial cells showing peroxidase activity varied from less than 10% to 85%. The peroxidase activity was present throughout the endoplasmic reticulum of these epithelial cells, extending from the perinuclear cistern to the most peripheral portions of the endoplasmic reticulum adjacent to the apical lumen. Biochemical assays of peroxidase activity in these endometria were compared with the ultrastructurally identified epithelial peroxidase and the endometrial granulocyte count. Uterine granulocyte peroxidase appeared to make a substantial contribution to the total peroxidase activity assayed by biochemical methods. Standard biochemical techniques alone, therefore were not considered to be adequate to evaluate epithelial peroxidase activity.
A Review on Tumor-Treating Fields (TTFields): Clinical Implications Inferred From Computational Modeling (2018)

Tumor-treating fields (TTFields) are a cancer treatment modality that uses alternating electric fields of intermediate frequency (∼100-500 kHz) and low intensity (1-3 V/cm) to disrupt cell division. TTFields are delivered by transducer arrays placed on the skin close to the tumor and act regionally and noninvasively to inhibit tumor growth. TTFields therapy is U.S. Food and Drug Administration approved for the treatment of glioblastoma multiforme, the most common and aggressive primary human brain cancer. Clinical trials testing the safety and efficacy of TTFields for other solid tumor types are underway. The objective of this paper is to review computational approaches used to characterize TTFields. The review covers studies of the macroscopic spatial distribution of TTFields generated in the human head, and of the microscopic field distribution in tumor cells. In addition, preclinical and clinical findings related to TTFields and principles of its operation are summarized. Particular emphasis is put on outlining the potential clinical value inferred from computational modeling.
Laser-assisted derivation of human embryonic stem cell lines from IVF embryos after preimplantation genetic diagnosis (2007)

These hESC lines can serve as an important model of the genetic disorders that they carry. Laser-assisted isolation of the ICMs may be applied for the derivation of new hESC lines in a xeno-free system for future clinical applications.
Differential patterns of DNA binding by myc and max proteins. (1993)

c-myc, N-myc, and L-myc genes are subject to highly variable degrees of tissue-specific regulation. Their aberrant expression has also been implicated in the pathogenesis of a variety of malignant tumors. The recently identified max protein dimerizes with c-myc to promote its sequence-specific DNA binding. max exists in two forms (long and short) that differ by virtue of a 9-amino acid insertion/deletion at the N terminus. We tested recombinant myc and max proteins for binding to six oligonucleotides containing related c-myc sites. Each myc protein, alone and in association with max proteins, manifested a unique pattern of DNA binding. Phosphorylation of both max proteins was observed when they were incubated in a rabbit reticulocyte lysate. This strongly affected DNA binding by max(long) but not by max(short). Our results point to the existence of specific DNA binding preferences for each of the myc proteins. The 9-amino acid segment that distinguishes max(long) from max(short) appears to serve a regulatory function that provides additional control over DNA sequence recognition.
232. A reaction of certain diazosulphonates derived from β-naphthol-1-sulphonic acid. Part XV. Derivatives of 2′-nitro-4′-methyl-benzene-2-naphthol-1-diazosulphonate and synthesis of 2-(2′-nitro-4′-methylphenylamino)isoindolinone-3-acetic acid (1936)

F. M. Rowe, A. S. Haigh and A. T. Peters, J. Chem. Soc., 1936, 1098 DOI: 10.1039/JR9360001098
TG1050, an immunotherapeutic to treat chronic hepatitis B, induces robust T cells and exerts an antiviral effect in HBV-persistent mice (2014)

Injection of TG1050 induced both splenic and intrahepatic functional T cells producing cytokines and displaying cytolytic activity in HBV-naïve and HBV-persistent mouse models together with significant reduction of circulating viral parameters. These results warrant clinical evaluation of TG1050 in the treatment of CHB.
Liquid chromatography/tandem mass spectrometry sensitivity enhancement via online sample dilution and trapping: applications in microdosing and dried blood spot (DBS) bioanalysis (2010)

A simple online sample dilution, enrichment, and cleanup technique was developed for sensitive microdosing and dried blood spot (DBS) liquid chromatography/tandem mass spectrometric (LC/MS/MS) bioanalysis. Samples are diluted online with water and enriched in a trap column which is subsequently switched inline with the analytical column. Excellent lansoprazole (in acetonitrile) peak shape is maintained even with an 80-microL injection. In comparison, similar chromatographic peaks were observed only when a small volume of the same solution, i.e., 1 microL, was injected on a regular high-performance liquid chromatography (HPLC) system, where an injection of 5 microL resulted in severe peak fronting. A substantial enhancement in sensitivity is realized in the trapping mode using large injection volumes. The trap column is washed at the beginning and at the end of each injection with aqueous and organic solvent respectively to remove matrix components. This ultimately leads to reduction of matrix effects and mass spectrometer noise, thus facilitating the utilization of protein precipitation as the sample preparation for plasma samples. A lower limit of quantitation (LLOQ) of 0.5 pg/mL was demonstrated for lansoprazole in human plasma with a signal-to-noise (S/N) ratio of 13 using a 100 microL injection. Excellent intra-day precision and accuracy were established for lansoprazole in human plasma with good linearity (R(2) > 0.999) from 0.5 to 500 pg/mL. This level of LLOQ makes LC/MS/MS a practical alternative for microdosing bioanalysis, where the dose is typically 100 times lower than the therapeutic dose. The same technique was applied to quantitate lansoprazole in human whole blood employing DBS technology. With a single 3-mm punch, i.e. approximately 2 microL of whole blood or approximately 1 microL plasma, a LLOQ of 0.1 ng/mL showed sufficient S/N ratio (40) for lansoprazole when 75 microL of extract was injected. In all, the online sample dilution, cleanup, and enrichment technique demonstrated the practical utility of LC/MS/MS in microdosing and DBS bioanalysis.
Sendai virus assembly: M protein binds to viral glycoproteins in transit through the secretory pathway (1993)

We have examined the relative ability of Sendai virus M (matrix) protein to associate with membranes containing viral glycoproteins at three distinct stages of the exocytic pathway prior to cell surface appearance. By the use of selective low-temperature incubations or the ionophore monensin, the transport of newly synthesized viral glycoproteins was restricted to either the pre-Golgi intermediate compartment (by incubation at 15 degrees C), the medial Golgi (in the presence of monensin), or the trans-Golgi network (by incubation at 20 degrees C). All three of these treatments resulted in a marked accumulation of the M protein on perinuclear Golgi-like membranes which in each case directly reflected the distribution of the viral F protein. Subsequent redistribution of the F protein to the plasma membrane by removal of the low-temperature (20 degrees C) block resulted in a concomitant redistribution of the M protein, thus implying association of the two components during intracellular transit. The extent of M protein-glycoprotein association was further examined by cell fractionation studies performed under each of the three restrictive conditions. Following equilibrium sedimentation of membranes derived from monensin-treated cells, approximately 40% of the recovered M protein was found to cofractionate with membranes containing the viral glycoproteins. Also, by flotation analyses, a comparable subpopulation of M protein was found to be membrane associated whether viral glycoproteins were restricted to the trans-Golgi network, the medial Golgi, or the pre-Golgi intermediate compartment. Additionally, transient expression of M protein alone from cloned cDNA showed that neither membrane association nor Golgi localization occurs in the absence of Sendai virus glycoproteins.
Dynamics of cervical langerhans cell counts in the course of HPV-positive CIN treatment with the use of human recombinant interferon gamma. (2005)

Our data strongly support the observation from static studies suggesting that regression of HPV-related cervical lesions is associated with increased density of epithelial Langerhans cells.
MUTUAL INFORMATION RELEVANCE NETWORKS: FUNCTIONAL GENOMIC CLUSTERING USING PAIRWISE ENTROPY MEASUREMENTS (1999)

Increasing numbers of methodologies are available to find functional genomic clusters in RNA expression data. We describe a technique that computes comprehensive pair-wise mutual information for all genes in such a data set. An association with a high mutual information means that one gene is non-randomly associated with another; we hypothesize this means the two are related biologically. By picking a threshold mutual information and using only associations at or above the threshold, we show how this technique was used on a public data set of 79 RNA expression measurements of 2,467 genes to construct 22 clusters, or Relevance Networks. The biological significance of each Relevance Network is explained.
Spurious Reporting of Nocturnal Hypoglycemia by CGMS in Patients With Tightly Controlled Type 1 Diabetes (2002)

CGMS reports of asymptomatic nighttime hypoglycemia may be spurious and should be interpreted with caution in patients with tightly controlled diabetes.
Meister Eckhart (1999)

1. 1326 wird ein fast siebzigjähriger Dominikaner angeklagt, der lange angesehen in der Leitung des Ordens gewirkt hatte und zweimal sogar den berühmten Lehrstuhl in Paris innehatte. Als dieser kurz darauf stirbt, wird das Urteil öffentlich gemacht. Der von der offiziellen Kirche zum Ketzer erklärte ist bald kaum noch bekannt. Erst 500 Jahre später kehrt sich das um: Eckhart wird zum Vorbild und Märtyrer moderner Religiosität, die den »Gott in mir« an die Stelle des vorgeschriebenen Gottes setzt. Die Verurteilung bestätigt das Urteil über ›die‹ Kirche: Der fromme Mensch als Vertreter einer ›modernen‹ individuellen Religiosität wurde von der Inquisition, als dem ›wahren Gesicht‹ institutioneller Religion, verdammt. Wie kommt es zu dieser Doppeldeutigkeit?
The envelope-associated 22K protein of human respiratory syncytial virus: nucleotide sequence of the mRNA and a related polytranscript (1985)

We recently determined that respiratory syncytial virus (strain A2) encodes a fourth unique envelope-associated virion protein that has molecular weight of approximately 24,000, as estimated by gel electrophoresis. The nucleotide sequence of the mRNA encoding this novel protein has now been determined from five cDNA clones, including three that contain the complete mRNA sequence. The complete mRNA sequence is 957 nucleotides, exclusive of polyadenylate, and contains two partially overlapping open reading frames. The 5'-proximal open reading frame is favored for utilization by the criteria of the location and sequence of its translational start site. Furthermore, the calculated molecular weight of the encoded protein, 22,153, is in agreement with the previous estimate of 24,000 for the authentic protein identified by hybrid selection and in vitro translation. The sequence of the predicted protein, now designated the 22K protein, contains 194 amino acids, is relatively hydrophilic, and appears to be the most basic of the respiratory syncytial virus proteins. The mRNA also contains a second, internal open reading frame which would encode a protein of 90 amino acids. However, no evidence for this translation product is known. The first nine nucleotides in the mRNA sequence, 5'-GGGGCAAAU, are identical to the conserved sequence identified previously at the 5' termini of seven other respiratory syncytial viral mRNAs; the sequence at the 3' end of the 22K mRNA, 5'. . . AGUUAUUU-polyadenylate, contains the elements of the previously identified 3'-terminal consensus sequence for respiratory syncytial virus mRNAs, AGUUAA(N)1-4-polyadenylate (P. L. Collins, Y. T. Huang, and G. W. Wertz, Proc. Natl. Acad. Sci. U.S.A. 81:7683-7687). In addition, we present and describe the intergenic sequence of a dicistronic RNA derived from readthrough of the F and 22K protein genes.
Folding and Function of I Domain-deleted Mac-1 and Lymphocyte Function-associated Antigen-1 (2000)

In those integrins that contain it, the I domain is a major ligand recognition site. The I domain is inserted between beta-sheets 2 and 3 of the predicted beta-propeller domain of the integrin alpha subunit. We deleted the I domain from the integrin alpha(M) and alpha(L) subunits to give I-less Mac-1 and lymphocyte function-associated antigen-1 (LFA-1), respectively. The I-less alpha(M) and alpha(L) subunits were expressed in association with the wild-type beta(2) subunit on the surface of transfected cells and bound to all the monoclonal antibodies mapped to the putative beta-propeller and C-terminal regions of the alpha(M) and alpha(L) subunits, suggesting that the folding of these domains is independent of the I domain. I-less Mac-1 bound to the ligands iC3b and factor X, but this binding was reduced compared with wild-type Mac-1. In contrast, I-less Mac-1 did not bind to fibrinogen or denatured bovine serum albumin. Binding to iC3b and factor X by I-less Mac-1 was inhibited by the function-blocking antibody CBRM1/32, which binds to the beta-propeller domain of the alpha(M) subunit. I-less LFA-1 did not bind its ligands intercellular adhesion molecule-1 and -3. Thus, the I domain is not essential for the folding, heterodimer formation, and surface expression of Mac-1 and LFA-1 and is required for binding to some ligands, but not others.